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Effect of taurine on toxicity of aluminum in rats
e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e187–e192
Contents lists available at ScienceDirect
e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism journal homepage: http://www.elsevier.com/locate/clnu
Original Article
Effect of taurine on toxicity of aluminum in rats Yen-Hung Yeh a, *, Ya-Ting Lee b, Hung-Sheng Hsieh c, Deng-Fwu Hwang d a
Department of Nutrition and Health Science, Toko University, Chia-Yi, Taiwan, ROC Department of Beauty Science, Chienkuo Technology University, Changhua, Taiwan, ROC c Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, ROC d Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan, ROC b
a r t i c l e i n f o
s u m m a r y
Article history: Received 14 September 2008 Accepted 27 May 2009
Background & aims: A study was undertaken to investigate the effect of taurine on the toxicity of aluminum in male Wistar rats.
Keywords: Aluminum Taurine Toxicity Hepatotoxicity Nephrotoxicity Rats
Methods: The rats were divided into six groups and fed different diets with or without 5% taurine and 150–300 ppm aluminum added for 2 months. Results: It was found that the body weight of rats, the ratios of liver and kidney weight to body weight, and the level of glutathione in the liver were decreased with increasing the dose of aluminum. The levels of aluminum in the liver and kidney, the levels of TBARS in the plasma and liver, the activities of AST and ALT in the plasma and the levels of BUN and creatinine in the plasma of rats were increased with the increasing dose of aluminum. Hence, symptoms of aluminum toxicity in rats included loss of body weight, hepatotoxicity and nephrotoxicity. Conclusions: However, these toxic effects of aluminum were significantly reduced when the rats fed diet with taurine added. Furthermore, the level of aluminum in the feces of rats treated with taurine and aluminum was higher than that of rats treated with aluminum alone. It indicated that taurine might play a role in reducing the toxic effect of aluminum in rats. Ó 2009 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
1. Introduction Aluminum toxicity was first recognized in patients to whom aluminum was administered parenterally, i.e. through renal dialysate1 and intravenous nutrient solution.2 Aluminum is proposed to be a factor contributing to several neurological disorders such as Alzheimer’s disease.3 There is evidence that exposure to aluminum from drinking water results in cognitive impairment and an increased incidence of Alzheimer’s disease.4 To understanding of a possible enhanced bioavailability of aluminum in this type of exposure or after other exposure such as antacid intake or industrial exposure need to be considered or explored. Although these points might be debatable, there is little doubt that accumulation of aluminum leads to tissue damage.5 That aluminum can be toxic to plants, animals, and humans is well documented, but the mechanism of action is poorly
* Corresponding author. Tel.: þ886 5 3622 889; fax: þ886 5 3622 899. E-mail address: [email protected] (Y.-H. Yeh).
understood.6–8 A clear example is the etiology of the microcytic anemia, osteomalasia, and encephalopathy that occur in renal failure patients as a result of the progressive accumulation of aluminum in this condition.8 Despite a large body of literature on the pathological effects of aluminum in biology, the underlying causes of tissue damage in renal failure, and in most other aluminum-related disorders, are largely matters of conjecture. This is partly a result of the wide variety of experimental conditions under which aluminum has been studied, many of which are in vivo. In our laboratory, we have been investigating the effects of dietary aluminum and taurine intake on mineral metabolism in vitro using animal models. Taurine is a sulfur containing amino acid that conjugates with bile acids in the liver9 and chemically similar to acetylcysteine, an agent for treating the heavy metal intoxication. It has been reported that taurine might possess a protective action against drug-induced injuries.10,11 Taurine may play an important role in reducing the toxic effect of copper, lead, oxidized fish oil, oxidized cholesterol and vitamin A in rats.12–17 As above description, aluminum is a modern toxic metal. Hence, it prompted us to investigate the effect of taurine on the toxicity of aluminum. In this study, the model used an evaluation of aluminum on dietary protection of taurine in the intestine was studied.
1751-4991/$ - see front matter Ó 2009 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.eclnm.2009.05.013
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2. Materials and methods
2.3. Levels of glutathione (GSH) measurement
2.1. Animals
GSH reacts non-enzymatically with 5, 5 dithiobis (2-nitrobenzoic acid) (DTNB) to yield glutathione disulfide (GSSG) and 2-nitro-5-thiobenzoic acid (TNB). GSSG is then reduced enzymatically by NADPH and glutathione reductase (GR) to regenerate GSH. Concentrations of DNTB, NADPH and GR are chosen such that the rate of the overall reaction is linearly proportional to the concentration of total glutathione. The rate of formation of TNB is followed spectrophotometrically, and assay is calibrated using standards. If the sample is reacted with 2-vinylpyridine, GSH is derivatized, and only GSSG is detected during subsequent assay.20
0
Male weanling Wistar rats were purchased from the National Laboratory Animal Center. They were kept in an air-conditioned room (23 1 C, 50–60% humidity) lit for 12 h per day (07:00– 19:00 h). After acclimating for 2 weeks with a commercial nonpurified diet (Rodent Laboratory Chow 5001, Pruida Co., USA), 36 rats were divided into six groups. Six rats in each group were assigned to receive an 8-week course of one of six formulated diets (Table 1). The diets were formulated as described previously by American Institute of Nutrition (AIN)18 because this formula is still commonly used in spite of new one recommended by AIN in 1993. The form of aluminum nitrate nonahydrate (analytical grade) was supplied by E. Merck (Germany). Water and food were always available. After feeding, all rats were weighed. The blood of the rats was taken at a 2 weeks interval from the tail vein. Then, the plasma samples were collected by centrifugation (2000 g, 15 min) from blood and examined for the level of thiobarbituric acid reactive substances (TBARS), and the activities of aspartate transaminase (AST) and alanine transaminase (ALT) in the plasma were also assayed by a Vitalab Selectra (E. Merck, Germany) with using an enzymatic kit. At the last 2 days of 8-week course of diets, the feces of rats were collected and assayed for aluminum level, and then rats were killed by exsanguinations from the inferior venal cava through a laparotomy incision with the animal under light ether anesthesia. The liver and kidney of rats were quickly excised without perfusion and weighed. Both ratios of liver and kidney weight to body weight were obtained. Then, the liver and kidney samples were stored at 40 C for aluminum, glutathione (GSH) and TBARS determinations. The plasma was analyzed for TBARS, AST, ALT, blood urea nitrogen (BUN) and creatinine. The levels of BUN and creatinine in the plasma were also assayed by a Vitalab Selectra with using enzymatic kit.
2.4. Aluminum measurement Aluminum contents of liver, kidney and feces were determined by atomic absorbance21 by a Hitachi Z-8100 Polarized Zeeman Atomic Absorbance Spectrophotometer (Japan). 2.5. Statistical analysis Statistical analysis for differences among rats in the experimental groups was performed by the 2-way analysis of variance procedure and Duncan’s new multiple range tests.22 A P-value <0.05 was considered statistically significant. 3. Results The effects of taurine and aluminum on the growth of rats are shown in Fig. 1. After 2-week feeding, the weight of the rat was significantly decreased (P < 0.05) when the concentration of aluminum in diet was more than 150 ppm, but significantly increased when the diet was with taurine added (P < 0.05). It also indicated that taurine could improve the growth of rats which fed
500
2.2. TBARS production
Table 1 Composition of the experimental diet in each group for test aluminum and taurine. Ingredient (%)
Dietsa
Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
f e
f
400
e
e
d
d
Body weight (g)
Lipid peroxidation activities in blood and liver were assayed by measurements of malondialdehyde (MDA), an end product of peroxidized fatty acids and thiobarbituric acid (TBA) reaction product. Twenty ml of plasma and 20% liver homogenate were separately mixed with 1.0 ml of 0.4% TBA in 0.2% HCl and 0.15 ml of 0.2% dibutylated toluene (BHT) in 95% ethanol. The samples were then incubated and analyzed with a fluorescence detector.19
Control Taurine Al 150 (ppm)
300
d
e
d c
b
c
c
c
b
b
b
c c
a
a
a
a 200
Control Taurine Al 150 Tau þ Al 150 Al 300 Tau þ Al 300 Sucrose 20 Casein 35 Corn starch 30 Cellulose 5 Corn oil 5 Methionine 0.3 Choline 0.2 AIN mineral mix 3.5 AIN vitamin mix 1 Taurine 0 Aluminum 0
20 35 25 5 5 0.3 0.2 3.5 1 5 0
20 20 35 35 29.985 24.985 5 5 5 5 0.3 0.3 0.2 0.2 3.5 3.5 1 1 0 5 0.015 0.015
20 35 29.97 5 5 0.3 0.2 3.5 1 0 0.03
20 35 24.97 5 5 0.3 0.2 3.5 1 5 0.03
a Taurine: 5% taurine in diet; Al 150: 150 ppm Al in diet; Tau þ Al 150: 5% taurine and 150 ppm Al in diet; Al 300: 300 ppm Al in diet; Tau þ Al 300: 5% taurine and 300 ppm Al in diet.
100
0
0
2
4
6
8
Weeks Fig. 1. Effect of aluminum and taurine on the body weight of rats. a–f: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b, c, d, e, f) in the figure means the statistical different groups in the same week.
Y.-H. Yeh et al. / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e187–e192
Kidney
b b
0.6 a a a a
d 150
c
aa a
2.5
b a
a
100
50
0
0
2
4
6
Fig. 3. Effect of aluminum and taurine on the activity of aspartate transaminase (AST) in the plasma of rats. a–e: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b, c, d, e) in the figure is to figure means the statistical different groups in the same week.
the taurine and aluminum added was higher than that of rats fed diet with only aluminum added (P < 0.05) (Fig. 6). The effects of taurine and aluminum on the level of BUN and creatinine in the plasma of rats are also shown in Fig. 6. After 8-week feeding, the level of BUN and creatinine in the plasma was higher in the groups fed diet with aluminum added than in control group. The level of BUN and creatinine in the plasma of rats was increased with the 100 Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
Control Taurine Al 150 (ppm)
e d
80
e
c
60
Liver
b b a a a a
b
c
c
b
b
d c
c 40
c
d
d
8
8
Weeks
Control Taurine Al 150 (ppm) Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
Weeks
c
b
a
0.2
3.0
c
d
b
c
c
d
d
d
d
c
e
e
b
0.4
0.0
Liver weight/ body weight (%)
Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
Control Taurine Al 150 (ppm)
ALT (U/L)
Kidney weight/ body weight (%)
0.8
200
AST (U/L)
diets with 150–300 ppm aluminum added. The effects of taurine and aluminum on the ratios of liver and kidney weight to body weight in rats are shown in Fig. 2. After 8-week feeding, the ratios of liver and kidney weight to body weight of rats fed with aluminum diet (either 150 or 300 ppm) were more significantly decreased than those of rats fed with control diet and taurine diet. However, the ratios of liver and kidney weight to body weight in rats fed diet taurine and aluminum added were not significantly different from those of rats fed diet aluminum added. This means that taurine might not significantly reduce the toxicity of aluminum in the rats based on the ratios of liver and kidney weight to body weight. The effects of taurine and aluminum on the activities of AST and ALT in the plasma are shown in Fig. 3 and Fig. 4. It was found that the activities of AST and ALT in the plasma of rats fed with aluminum added were gradually increased with the feeding time course. The activities of AST and ALT in the plasma of rats are increased with the increasing level of aluminum. The activities of AST and ALT in those rats fed diet with taurine added were significantly to reduce the toxicity of aluminum (P < 0.05), indicating taurine might play protective effect on aluminum toxicity in rats. The effects of taurine and aluminum on the TBARS production in the plasma in rats are shown in Fig. 5. After 8-week feeding, the level of TBARS in the plasma of rats fed with added of aluminum was higher than that of control group (P < 0.05). After 8-week feeding, the level of TBARS in the liver of rats fed with added of aluminum was also higher than that of control group (Fig. 6) (P < 0.05). The level of TBARS in the plasma and liver of rats was somewhat increased with the increasing in the concentration of aluminum in diet. The level of TBARS in the liver of rats fed diet was less than that of rats fed diet with aluminum added only (P < 0.05), but the plasma of rats was not (P > 0.05). The level of GSH in the liver of rats was decreased with the increasing the concentration of aluminum in diet. The level of GSH in the liver of rats fed diet with
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b a
aa
aa
aa
a
2.0 1.5
20
1.0 0.5 0.0
8
Weeks Fig. 2. Effect of aluminum and taurine on the ratios of liver and kidney weight to body weight in rats after 8-week feeding. a, b: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b) in the figure means the statistical different groups in the same week.
0
0
2
4
6
8
Weeks Fig. 4. Effect of aluminum and taurine on the activity of alanine transaminase (ALT) in the plasma of rats. a–e: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b, c, d, e) in the figure means the statistical different groups in the same week.
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increasing dose of aluminum in the diet. When the diet was with taurine added, the level of BUN and creatinine was significantly reduced (P < 0.05). The effects of taurine and aluminum on the level of aluminum in the liver, kidney and feces of rats are shown in Fig. 7. After 8-week feeding, the level of aluminum in the liver, kidney and feces was obviously higher in the groups fed diet with aluminum added than in control group. The level of aluminum in the liver, kidney and feces was increased with the increasing dose of aluminum in the diet. When the diet was with taurine added, the level of aluminum in the liver and kidney was significantly reduced, and the level of aluminum in the feces was slightly increased (P < 0.05).
4 Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
Control Taurine Al 150 (ppm)
d
TBARS level (nM/ml)
3
d c
c c
c
b b
c
a
b
2 bbbb
aa
c
c
a
aa
4. Discussion
aa
In this study, the toxic effect of aluminum in rats was not severe than that of copper and lead.12,13 The symptoms of aluminum toxicity in rats included reduced body weight, ratios of liver and kidney weight to body weight, and level of GSH in the liver, and increasing activities of AST and ALT in the plasma, levels of TBARS, BUN and creatinine in the plasma and/or liver, and concentrations of aluminum in the liver and kidney of rats. In the clinical plasma examination, the activities of AST and ALT in plasma represent biomarkers for liver functions.23 The activities of AST and ALT in the plasma of rats were significantly elevated by aluminum, indicating aluminum-related injury to the liver. This result is also reported by other papers.24,25 Since taurine significantly reduced the AST and ALT activities in the plasma of rat, the hepatic injury by aluminum could be ameliorated by taurine. This result was similar to that of body weight in rats. However, the levels of TBARS and GSH in the
1
0
0
2
4
6
8
Weeks Fig. 5. Effect of aluminum and taurine on the level of thiobarbituric acid reactive substances (TBARS) in the plasma of rats. a–d: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b, c, d) in the figure means the statistical different groups in the same week.
12 e
80 d 60
c b
40
a
a
20
0
GSH (μΜ/g weight liver)
TBARS (μΜ/g weight liver)
100
10
d Control Taurine Al 150 (ppm) Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
8 6 c b
4
b a
2 0
8
8
Weeks
Weeks 80
d
1.0
e
d c
BUN (mg/dl)
c 40
20
0
a
b
b
0.8
Creatinine (mg/dl)
dd
60
c
aa 0.6
0.4
0.2
8
Weeks
0.0
8
Weeks
Fig. 6. Effect of aluminum and taurine on the levels of TBARS and GSH in the liver and BUN and creatinine in the plasma of rats after 8-week feeding. a–e: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b, c, d, e) in the figure means the statistical different groups in the same week.
Y.-H. Yeh et al. / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e187–e192
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2500 Feces d
Al (ppm)
2000
Control Taurine Al 150 (ppm) Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
c
1500 b a 1000
500
0
8
Weeks 350
80 Liver c
300 b
40
c
250
a
Al (ppm)
Al (ppm)
60
d
Kidney
d
200 150
b a
100
20
50 0
8
Weeks
0
8
Weeks
Fig. 7. Effect of aluminum and taurine on the level of aluminum in the liver, kidney and serum of rats after 8-week feeding. a–d: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b, c, d) in the figure means the statistical different groups in the same week.
liver are additional indicators of liver injury. TBARS is an end product of lipid peroxidation. The level of TBARS of the plasma and liver was increased with the increasing dose of aluminum and the level of TBARS of the plasma was also increased with exposure time. The data do not prove that the mechanism of aluminum injury is by lipid peroxidation but it is strongly suggestive that it plays an important role. Other paper also indicated that aluminum might increase the level of TBARS in the tissues of experimental animal.4,25 The level of TBARS in the plasma and liver of rat was significantly reduced when the rats were fed diet with the taurine added. The level of GSH in the liver of rats was reduced by aluminum, which was similar to that of other report.26,27 While it was raised significantly when the rats were fed diet with the taurine added. It means that taurine may play an important role in the metabolism of GSH and in preventing lipid peroxidation but these related mechanism should be studied further. On the other hand, the levels of BUN and creatinine in the plasma of rats are tested as indicators for kidney functions.25,28 Judging from both indicators and the ratio of kidney weight to body weight, aluminum significantly induced the dysfunction of kidney. Although with taurine added in diet did not ameliorate the ratio of kidney weight to body weight, the levels of BUN and creatinine in the plasma of rats were significantly reduced when the rats were fed diet with taurine added. Furthermore, the level of aluminum in the liver and kidney was significantly increased with increasing exposure to aluminum in the diet. The accumulated amount of aluminum was higher in the kidney than in the liver, which was the same as previous report.29 Lipid peroxidation is a chemical mechanism capable of disrupting the structure and the function of the biological membranes that
occurs as a result of free radical attack on lipids. When reactive oxygen species (ROS) begin to accumulate, hepatic cells exhibit a defensive mechanism by using various antioxidant enzymes. The main detoxifying systems for peroxides are catalase and GSH.30 Catalase is an antioxidant enzyme, which destroys H2O2 that can form a highly reactive hydroxyl radical in presence of iron as a catalyst.31 By participating in the glutathione redox cycle, GSH together with GSH-Px convert H2O2 and lipid peroxides to non-toxic products. Reduced activity of one or more antioxidant systems due to the direct toxic effect of aluminum leads to increase lipid peroxidation, oxidative stress and hepatotoxicity. In the current study, aluminum depleted GSH stores and reduced catalase and GSH-Px activities. These results are in harmony with other investigations.32 For example, aluminum induced hepatotoxicity was exacerbated by GSH depletion. In the current study, depletion of GSH stores can account for the inhibition of GSH-Px activity. In addition, high levels of peroxides may explain catalase activity inhibition.33 On the other hand, taurine can also function as a regulator of intracellular calcium homeostasis34 that can be disturbed due to aluminum toxicity. Taurine has been shown to protect against endothelial cell death by modulating intracellular calcium fluxes.35 Finally, taurine may ameliorate aluminum induced hepatic injury by enhancing the activities of endogenous antioxidants. Support for this concept comes from our results, which show that taurine produced a remarkable significant increase in hepatic GSH level and GSH-Px and catalase activities. This could be attributed to the role of taurine in maintaining a normal IGF-I level36 (Dawson et al., 1999) and its antioxidant action against lipid peroxidation, thus conserving the internal antioxidants system. The stimulatory effect of taurine on endogenous antioxidants was reported by others.37,38
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Together, the results of the present study demonstrate that administration of taurine has a therapeutic role in preventing cyclosporine-induced hepatotoxicity, possibly through its unique cytoprotective properties such as antioxidant activity. Accumulation of aluminum is the net consequence of uptake, biotransformation and elimination processes within an individual. Once aluminum is absorbed, it may be transformed into aluminumthionein or metallothionein. Although the half-life of aluminumthionein in the liver and kidney is not known exactly, it is many years.39 With continued retention, there is progressive accumulation in these tissues. The accumulated amount of aluminum in the tissue was effectively reduced by taurine. Taurine is a special amino acid, which possesses an amino group and a sulfonate group. These functional groups might bind with heavy metals, and then stimulated the excretion of such compounds. In this study, it was also found that the amount of aluminum in the feces of rats fed with taurine added was slightly increased. There is no evidence that taurine directly reduces the production of free radicals but it may well operate by binding aluminum which is then not absorbed or is more rapidly excreted. In other words it may act by reducing the overall bioavailability of aluminum or the intracellular availability of absorbed aluminum. Hence, dietary taurine may play a role to reduce the toxic effect of aluminum in the liver and kidney of rats. Conflicts of interest All authors have no Conflict of interest. Acknowledgement Y-H Yeh conducted the study design, experiment and wrote the manuscript. Y-T Lee and H-S Hsieh analyzed the data and statistical analysis. D-F Hwang performed data interpretation. All authors contributed to this study and reviewed the manuscript. References 1. Hewitt CD, Savory J, Wills MR. Aspects of aluminum toxicity. Clin Lab Med 1990;10:403–7. 2. Greyer JL, Powers CF. Assessment of exposure to parenteral and oral aluminum with and without citrate using a deferrioxamine test in rats. Toxicology 1992;76:119–32. 3. Fraga CG, Oteiza PI, Golub MS, Gershwin ME, Keen CL. Effect of aluminum on brain lipid peroxidation. Toxicol Lett 1990;51:213–9. 4. Savory J, Exley C, Forbes WF. Can the controversy of the role of aluminum in Alzheimer’s disease be resolved? What are the suggestive approaches to this controversy and methodological issues to be considered? J Toxicol Environ Health 1996;48:615–35. 5. Quartely B, Esselmont G, Taylor A, Dobrota M. Effect of oral aluminum citrate on short-term tissue distribution of aluminum. Food Chem Toxicol 1993;31:543–8. 6. Committee on Nutrition. Aluminum toxicity in infants and children. Pediatrics 1996;97:413–6. 7. Flaten TP, Alfrey AC, Birchall JD, Savory J, Yokel RA. Status and future concerns of clinical and environmental aluminum toxicology. J Toxicol Environ Health 1996;48:527–41. 8. Jeffery EH, Abreo K, Burgess E, Cannata J, Greger JL. Systemic aluminum toxicity: effects on bone, hematopoietic tissue, and kidney. J Toxicol Environ Health 1996;48:649–65.
9. Jacobsen JG, Smith LHJ. Biochemistry and physiology of taurine and taurine derivatives. Physiol Rev 1968;48:425–33. 10. Tokunaga H, Yoneda Y, Kuriyama K. Protective actions of taurine against streptozotocin-induced hyperglycemia. Biochem Pharmacol 1979;28:2807–18. 11. Hamaguchi T, Azuma J, Awata N, Ohta H, Takihara K, Harada H. Reduction of doxorubicin induced cardiotoxicity in mice by taurine. Res Commun Chem Pathol Pharmacol 1988;59:21–8. 12. Wang LC, Hwang DF, Jeng SS, Cheng HM. Effect of high dose of dietary taurine on toxicity of lead in rats. J Chin Agric Chem Soc 1997;35:612–8. 13. Hwang DF, Wang LC, Cheng HM. Effect of taurine on toxicity of copper in rats. Food Chem Toxicol 1998;36:239–46. 14. Hwang DF, Hour JL, Cheng HM. Effect of taurine on toxicity of oxidized fish oil in rats. Food Chem Toxicol 2000;38:585–96. 15. Yeh YH, Lee YT, Hsieh HS, Hwang DF. Effect of taurine on toxicity of vitamin A in rats. Food Chem 2008;106:260–8. 16. Yeh YH, Chen MH, Lee YT, Hsieh HS, Hwang DF. Effect of taurine on toxicity of oxidized cholesterol in rats. J Food Drug Anal 2008;16:74–82. 17. Yeh YH, Chen MH, Lee YT, Hsieh HS, Hwang DF. Effect of taurine on toxicity of oxidized cholesterol and oxidized fish oil in rats. J Food Drug Anal 2008;16: 76–85. 18. American Institute of Nutrition. Report of the American institute ad hoc committee on standards for nutritional studies. J Nutr 1977;107:1340–8. 19. Tatum VL, Changchit C, Chow CK. Measurement of malondialdehyde by high performance liquid chromatography with fluorescence detection. Lipids 1990;25:226–33. 20. Griffith OW. Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 1980;106:207–13. 21. Horwitz W. Official methods of analysis. 14th ed. Washington: AOAC; 1984. 22. Puri SC, Mullen K. Multiple comparisons. In: Hall GK, editor. Applied statistics for food and agricultural scientists. Boston: Medical; 1980. 23. Ronald L, Koretz MD. Chronic hepatitis: science and superstition. In: Gitnick G, editor. Current hepatology. Chicago: Mosby-Year; 1992. 24. Flora SJS, Dhawan M, Tandon SK. Effects of combined exposure to aluminum and ethanol on aluminum body burden and some hepatic and haematopoietic biochemical variables in the rat. Hum Exp Toxicol 1991;10:45–8. 25. Domingo JL, Llobet JM, Gomez M, Tomas JM, Corbella J. Nutritional and toxicological effects of short term ingestion of aluminum by rats. Res Commun Chem Pathol Pharmacol 1991;57:129–32. 26. Alfrey AC. Physiology of aluminum in man. In: Gitelman HJ, editor. Aluminum and health: a critcal review. New York: Marcel Dekker; 1989. p. 101–24. 27. Winship KA. Toxicity of aluminum: a historical review. Part 2. Adverse drug react. Toxicol Rev 1993;12:177–211. 28. Guyton C. Textbook of medical physiology. New York: Saunders; 1991. 29. Hicks JS, Hackett DS, Sprague GL. Toxicity and aluminum concentration in bone following dietary administration of two sodium aluminum phosphate formulations in rats. Food Chem Toxicol 1987;25:533–8. 30. Meister A. Selective modification of glutathione metabolism. Science 1983;22:472–8. 31. Gutteridg JMC. Lipid peroxidation and antioxidant as biomarkers of tissue damage. Clin Chem 1995;14:1819–28. 32. Al Khader A, Al Sulaiman M, Kishore PN, Morais C, Tariq M. Quinacrine attenuates cyclosporine-induced nephrotoxicity in rats. Transplantation 1996;62:427–35. 33. Ghadermarzi M, Moosavi-Movahedi AA. Determination of the kinetic parameters for the ‘‘suicide substrate’’ inactivation of bovine liver catalase by hydrogen peroxide. J Enzym Inhib 1996;10:167–75. 34. Huxtable RJ. Physiological actions of taurine. Physiol Rev 1992;72:101–63. 35. Wang JH, Redmond HP, Watson RWG, Condron C, Bouchier-Hayes D. The beneficial effect of taurine on the prevention of human endothelial cell death. Shock 1996;6:331–8. 36. Dawson JR, Liu S, Eppler B, Patterson T. Effects of dietary taurine supplementation or deprivation in aged male Fischer 344 rats. Mech Ageing Dev 1999;107: 73–91. 37. Erdem A, Gundogan NU, Usubutun A, Kiine K, Erdem RS, Kara A, et al. The protective effect of taurine against gentamicin-induced acute tubular necrosis in rats. Nephrol Dial Transplant 2000;15:1175–82. 38. Saad SY, Al-Rikabi AC. Protection effects of taurine supplementation against cisplatin-induced nephrotoxicity in rats. Chemotherapy 2002;48:42–8. 39. Goyer RA. Toxic effects of metals. In: Klaassen CD, editor. Casarett & Doull’s toxicology: the basic science of poisons. 5th ed. New York: McGraw-Hill; 1996.
Contents lists available at ScienceDirect
e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism journal homepage: http://www.elsevier.com/locate/clnu
Original Article
Effect of taurine on toxicity of aluminum in rats Yen-Hung Yeh a, *, Ya-Ting Lee b, Hung-Sheng Hsieh c, Deng-Fwu Hwang d a
Department of Nutrition and Health Science, Toko University, Chia-Yi, Taiwan, ROC Department of Beauty Science, Chienkuo Technology University, Changhua, Taiwan, ROC c Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, ROC d Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan, ROC b
a r t i c l e i n f o
s u m m a r y
Article history: Received 14 September 2008 Accepted 27 May 2009
Background & aims: A study was undertaken to investigate the effect of taurine on the toxicity of aluminum in male Wistar rats.
Keywords: Aluminum Taurine Toxicity Hepatotoxicity Nephrotoxicity Rats
Methods: The rats were divided into six groups and fed different diets with or without 5% taurine and 150–300 ppm aluminum added for 2 months. Results: It was found that the body weight of rats, the ratios of liver and kidney weight to body weight, and the level of glutathione in the liver were decreased with increasing the dose of aluminum. The levels of aluminum in the liver and kidney, the levels of TBARS in the plasma and liver, the activities of AST and ALT in the plasma and the levels of BUN and creatinine in the plasma of rats were increased with the increasing dose of aluminum. Hence, symptoms of aluminum toxicity in rats included loss of body weight, hepatotoxicity and nephrotoxicity. Conclusions: However, these toxic effects of aluminum were significantly reduced when the rats fed diet with taurine added. Furthermore, the level of aluminum in the feces of rats treated with taurine and aluminum was higher than that of rats treated with aluminum alone. It indicated that taurine might play a role in reducing the toxic effect of aluminum in rats. Ó 2009 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
1. Introduction Aluminum toxicity was first recognized in patients to whom aluminum was administered parenterally, i.e. through renal dialysate1 and intravenous nutrient solution.2 Aluminum is proposed to be a factor contributing to several neurological disorders such as Alzheimer’s disease.3 There is evidence that exposure to aluminum from drinking water results in cognitive impairment and an increased incidence of Alzheimer’s disease.4 To understanding of a possible enhanced bioavailability of aluminum in this type of exposure or after other exposure such as antacid intake or industrial exposure need to be considered or explored. Although these points might be debatable, there is little doubt that accumulation of aluminum leads to tissue damage.5 That aluminum can be toxic to plants, animals, and humans is well documented, but the mechanism of action is poorly
* Corresponding author. Tel.: þ886 5 3622 889; fax: þ886 5 3622 899. E-mail address: [email protected] (Y.-H. Yeh).
understood.6–8 A clear example is the etiology of the microcytic anemia, osteomalasia, and encephalopathy that occur in renal failure patients as a result of the progressive accumulation of aluminum in this condition.8 Despite a large body of literature on the pathological effects of aluminum in biology, the underlying causes of tissue damage in renal failure, and in most other aluminum-related disorders, are largely matters of conjecture. This is partly a result of the wide variety of experimental conditions under which aluminum has been studied, many of which are in vivo. In our laboratory, we have been investigating the effects of dietary aluminum and taurine intake on mineral metabolism in vitro using animal models. Taurine is a sulfur containing amino acid that conjugates with bile acids in the liver9 and chemically similar to acetylcysteine, an agent for treating the heavy metal intoxication. It has been reported that taurine might possess a protective action against drug-induced injuries.10,11 Taurine may play an important role in reducing the toxic effect of copper, lead, oxidized fish oil, oxidized cholesterol and vitamin A in rats.12–17 As above description, aluminum is a modern toxic metal. Hence, it prompted us to investigate the effect of taurine on the toxicity of aluminum. In this study, the model used an evaluation of aluminum on dietary protection of taurine in the intestine was studied.
1751-4991/$ - see front matter Ó 2009 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.eclnm.2009.05.013
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2. Materials and methods
2.3. Levels of glutathione (GSH) measurement
2.1. Animals
GSH reacts non-enzymatically with 5, 5 dithiobis (2-nitrobenzoic acid) (DTNB) to yield glutathione disulfide (GSSG) and 2-nitro-5-thiobenzoic acid (TNB). GSSG is then reduced enzymatically by NADPH and glutathione reductase (GR) to regenerate GSH. Concentrations of DNTB, NADPH and GR are chosen such that the rate of the overall reaction is linearly proportional to the concentration of total glutathione. The rate of formation of TNB is followed spectrophotometrically, and assay is calibrated using standards. If the sample is reacted with 2-vinylpyridine, GSH is derivatized, and only GSSG is detected during subsequent assay.20
0
Male weanling Wistar rats were purchased from the National Laboratory Animal Center. They were kept in an air-conditioned room (23 1 C, 50–60% humidity) lit for 12 h per day (07:00– 19:00 h). After acclimating for 2 weeks with a commercial nonpurified diet (Rodent Laboratory Chow 5001, Pruida Co., USA), 36 rats were divided into six groups. Six rats in each group were assigned to receive an 8-week course of one of six formulated diets (Table 1). The diets were formulated as described previously by American Institute of Nutrition (AIN)18 because this formula is still commonly used in spite of new one recommended by AIN in 1993. The form of aluminum nitrate nonahydrate (analytical grade) was supplied by E. Merck (Germany). Water and food were always available. After feeding, all rats were weighed. The blood of the rats was taken at a 2 weeks interval from the tail vein. Then, the plasma samples were collected by centrifugation (2000 g, 15 min) from blood and examined for the level of thiobarbituric acid reactive substances (TBARS), and the activities of aspartate transaminase (AST) and alanine transaminase (ALT) in the plasma were also assayed by a Vitalab Selectra (E. Merck, Germany) with using an enzymatic kit. At the last 2 days of 8-week course of diets, the feces of rats were collected and assayed for aluminum level, and then rats were killed by exsanguinations from the inferior venal cava through a laparotomy incision with the animal under light ether anesthesia. The liver and kidney of rats were quickly excised without perfusion and weighed. Both ratios of liver and kidney weight to body weight were obtained. Then, the liver and kidney samples were stored at 40 C for aluminum, glutathione (GSH) and TBARS determinations. The plasma was analyzed for TBARS, AST, ALT, blood urea nitrogen (BUN) and creatinine. The levels of BUN and creatinine in the plasma were also assayed by a Vitalab Selectra with using enzymatic kit.
2.4. Aluminum measurement Aluminum contents of liver, kidney and feces were determined by atomic absorbance21 by a Hitachi Z-8100 Polarized Zeeman Atomic Absorbance Spectrophotometer (Japan). 2.5. Statistical analysis Statistical analysis for differences among rats in the experimental groups was performed by the 2-way analysis of variance procedure and Duncan’s new multiple range tests.22 A P-value <0.05 was considered statistically significant. 3. Results The effects of taurine and aluminum on the growth of rats are shown in Fig. 1. After 2-week feeding, the weight of the rat was significantly decreased (P < 0.05) when the concentration of aluminum in diet was more than 150 ppm, but significantly increased when the diet was with taurine added (P < 0.05). It also indicated that taurine could improve the growth of rats which fed
500
2.2. TBARS production
Table 1 Composition of the experimental diet in each group for test aluminum and taurine. Ingredient (%)
Dietsa
Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
f e
f
400
e
e
d
d
Body weight (g)
Lipid peroxidation activities in blood and liver were assayed by measurements of malondialdehyde (MDA), an end product of peroxidized fatty acids and thiobarbituric acid (TBA) reaction product. Twenty ml of plasma and 20% liver homogenate were separately mixed with 1.0 ml of 0.4% TBA in 0.2% HCl and 0.15 ml of 0.2% dibutylated toluene (BHT) in 95% ethanol. The samples were then incubated and analyzed with a fluorescence detector.19
Control Taurine Al 150 (ppm)
300
d
e
d c
b
c
c
c
b
b
b
c c
a
a
a
a 200
Control Taurine Al 150 Tau þ Al 150 Al 300 Tau þ Al 300 Sucrose 20 Casein 35 Corn starch 30 Cellulose 5 Corn oil 5 Methionine 0.3 Choline 0.2 AIN mineral mix 3.5 AIN vitamin mix 1 Taurine 0 Aluminum 0
20 35 25 5 5 0.3 0.2 3.5 1 5 0
20 20 35 35 29.985 24.985 5 5 5 5 0.3 0.3 0.2 0.2 3.5 3.5 1 1 0 5 0.015 0.015
20 35 29.97 5 5 0.3 0.2 3.5 1 0 0.03
20 35 24.97 5 5 0.3 0.2 3.5 1 5 0.03
a Taurine: 5% taurine in diet; Al 150: 150 ppm Al in diet; Tau þ Al 150: 5% taurine and 150 ppm Al in diet; Al 300: 300 ppm Al in diet; Tau þ Al 300: 5% taurine and 300 ppm Al in diet.
100
0
0
2
4
6
8
Weeks Fig. 1. Effect of aluminum and taurine on the body weight of rats. a–f: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b, c, d, e, f) in the figure means the statistical different groups in the same week.
Y.-H. Yeh et al. / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e187–e192
Kidney
b b
0.6 a a a a
d 150
c
aa a
2.5
b a
a
100
50
0
0
2
4
6
Fig. 3. Effect of aluminum and taurine on the activity of aspartate transaminase (AST) in the plasma of rats. a–e: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b, c, d, e) in the figure is to figure means the statistical different groups in the same week.
the taurine and aluminum added was higher than that of rats fed diet with only aluminum added (P < 0.05) (Fig. 6). The effects of taurine and aluminum on the level of BUN and creatinine in the plasma of rats are also shown in Fig. 6. After 8-week feeding, the level of BUN and creatinine in the plasma was higher in the groups fed diet with aluminum added than in control group. The level of BUN and creatinine in the plasma of rats was increased with the 100 Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
Control Taurine Al 150 (ppm)
e d
80
e
c
60
Liver
b b a a a a
b
c
c
b
b
d c
c 40
c
d
d
8
8
Weeks
Control Taurine Al 150 (ppm) Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
Weeks
c
b
a
0.2
3.0
c
d
b
c
c
d
d
d
d
c
e
e
b
0.4
0.0
Liver weight/ body weight (%)
Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
Control Taurine Al 150 (ppm)
ALT (U/L)
Kidney weight/ body weight (%)
0.8
200
AST (U/L)
diets with 150–300 ppm aluminum added. The effects of taurine and aluminum on the ratios of liver and kidney weight to body weight in rats are shown in Fig. 2. After 8-week feeding, the ratios of liver and kidney weight to body weight of rats fed with aluminum diet (either 150 or 300 ppm) were more significantly decreased than those of rats fed with control diet and taurine diet. However, the ratios of liver and kidney weight to body weight in rats fed diet taurine and aluminum added were not significantly different from those of rats fed diet aluminum added. This means that taurine might not significantly reduce the toxicity of aluminum in the rats based on the ratios of liver and kidney weight to body weight. The effects of taurine and aluminum on the activities of AST and ALT in the plasma are shown in Fig. 3 and Fig. 4. It was found that the activities of AST and ALT in the plasma of rats fed with aluminum added were gradually increased with the feeding time course. The activities of AST and ALT in the plasma of rats are increased with the increasing level of aluminum. The activities of AST and ALT in those rats fed diet with taurine added were significantly to reduce the toxicity of aluminum (P < 0.05), indicating taurine might play protective effect on aluminum toxicity in rats. The effects of taurine and aluminum on the TBARS production in the plasma in rats are shown in Fig. 5. After 8-week feeding, the level of TBARS in the plasma of rats fed with added of aluminum was higher than that of control group (P < 0.05). After 8-week feeding, the level of TBARS in the liver of rats fed with added of aluminum was also higher than that of control group (Fig. 6) (P < 0.05). The level of TBARS in the plasma and liver of rats was somewhat increased with the increasing in the concentration of aluminum in diet. The level of TBARS in the liver of rats fed diet was less than that of rats fed diet with aluminum added only (P < 0.05), but the plasma of rats was not (P > 0.05). The level of GSH in the liver of rats was decreased with the increasing the concentration of aluminum in diet. The level of GSH in the liver of rats fed diet with
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b a
aa
aa
aa
a
2.0 1.5
20
1.0 0.5 0.0
8
Weeks Fig. 2. Effect of aluminum and taurine on the ratios of liver and kidney weight to body weight in rats after 8-week feeding. a, b: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b) in the figure means the statistical different groups in the same week.
0
0
2
4
6
8
Weeks Fig. 4. Effect of aluminum and taurine on the activity of alanine transaminase (ALT) in the plasma of rats. a–e: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b, c, d, e) in the figure means the statistical different groups in the same week.
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increasing dose of aluminum in the diet. When the diet was with taurine added, the level of BUN and creatinine was significantly reduced (P < 0.05). The effects of taurine and aluminum on the level of aluminum in the liver, kidney and feces of rats are shown in Fig. 7. After 8-week feeding, the level of aluminum in the liver, kidney and feces was obviously higher in the groups fed diet with aluminum added than in control group. The level of aluminum in the liver, kidney and feces was increased with the increasing dose of aluminum in the diet. When the diet was with taurine added, the level of aluminum in the liver and kidney was significantly reduced, and the level of aluminum in the feces was slightly increased (P < 0.05).
4 Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
Control Taurine Al 150 (ppm)
d
TBARS level (nM/ml)
3
d c
c c
c
b b
c
a
b
2 bbbb
aa
c
c
a
aa
4. Discussion
aa
In this study, the toxic effect of aluminum in rats was not severe than that of copper and lead.12,13 The symptoms of aluminum toxicity in rats included reduced body weight, ratios of liver and kidney weight to body weight, and level of GSH in the liver, and increasing activities of AST and ALT in the plasma, levels of TBARS, BUN and creatinine in the plasma and/or liver, and concentrations of aluminum in the liver and kidney of rats. In the clinical plasma examination, the activities of AST and ALT in plasma represent biomarkers for liver functions.23 The activities of AST and ALT in the plasma of rats were significantly elevated by aluminum, indicating aluminum-related injury to the liver. This result is also reported by other papers.24,25 Since taurine significantly reduced the AST and ALT activities in the plasma of rat, the hepatic injury by aluminum could be ameliorated by taurine. This result was similar to that of body weight in rats. However, the levels of TBARS and GSH in the
1
0
0
2
4
6
8
Weeks Fig. 5. Effect of aluminum and taurine on the level of thiobarbituric acid reactive substances (TBARS) in the plasma of rats. a–d: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b, c, d) in the figure means the statistical different groups in the same week.
12 e
80 d 60
c b
40
a
a
20
0
GSH (μΜ/g weight liver)
TBARS (μΜ/g weight liver)
100
10
d Control Taurine Al 150 (ppm) Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
8 6 c b
4
b a
2 0
8
8
Weeks
Weeks 80
d
1.0
e
d c
BUN (mg/dl)
c 40
20
0
a
b
b
0.8
Creatinine (mg/dl)
dd
60
c
aa 0.6
0.4
0.2
8
Weeks
0.0
8
Weeks
Fig. 6. Effect of aluminum and taurine on the levels of TBARS and GSH in the liver and BUN and creatinine in the plasma of rats after 8-week feeding. a–e: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b, c, d, e) in the figure means the statistical different groups in the same week.
Y.-H. Yeh et al. / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e187–e192
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2500 Feces d
Al (ppm)
2000
Control Taurine Al 150 (ppm) Tau+Al 150 (ppm) Al 300 (ppm) Tau+Al 300 (ppm)
c
1500 b a 1000
500
0
8
Weeks 350
80 Liver c
300 b
40
c
250
a
Al (ppm)
Al (ppm)
60
d
Kidney
d
200 150
b a
100
20
50 0
8
Weeks
0
8
Weeks
Fig. 7. Effect of aluminum and taurine on the level of aluminum in the liver, kidney and serum of rats after 8-week feeding. a–d: values in the same week with different superscript are significantly different (P < 0.05). The lettering (a, b, c, d) in the figure means the statistical different groups in the same week.
liver are additional indicators of liver injury. TBARS is an end product of lipid peroxidation. The level of TBARS of the plasma and liver was increased with the increasing dose of aluminum and the level of TBARS of the plasma was also increased with exposure time. The data do not prove that the mechanism of aluminum injury is by lipid peroxidation but it is strongly suggestive that it plays an important role. Other paper also indicated that aluminum might increase the level of TBARS in the tissues of experimental animal.4,25 The level of TBARS in the plasma and liver of rat was significantly reduced when the rats were fed diet with the taurine added. The level of GSH in the liver of rats was reduced by aluminum, which was similar to that of other report.26,27 While it was raised significantly when the rats were fed diet with the taurine added. It means that taurine may play an important role in the metabolism of GSH and in preventing lipid peroxidation but these related mechanism should be studied further. On the other hand, the levels of BUN and creatinine in the plasma of rats are tested as indicators for kidney functions.25,28 Judging from both indicators and the ratio of kidney weight to body weight, aluminum significantly induced the dysfunction of kidney. Although with taurine added in diet did not ameliorate the ratio of kidney weight to body weight, the levels of BUN and creatinine in the plasma of rats were significantly reduced when the rats were fed diet with taurine added. Furthermore, the level of aluminum in the liver and kidney was significantly increased with increasing exposure to aluminum in the diet. The accumulated amount of aluminum was higher in the kidney than in the liver, which was the same as previous report.29 Lipid peroxidation is a chemical mechanism capable of disrupting the structure and the function of the biological membranes that
occurs as a result of free radical attack on lipids. When reactive oxygen species (ROS) begin to accumulate, hepatic cells exhibit a defensive mechanism by using various antioxidant enzymes. The main detoxifying systems for peroxides are catalase and GSH.30 Catalase is an antioxidant enzyme, which destroys H2O2 that can form a highly reactive hydroxyl radical in presence of iron as a catalyst.31 By participating in the glutathione redox cycle, GSH together with GSH-Px convert H2O2 and lipid peroxides to non-toxic products. Reduced activity of one or more antioxidant systems due to the direct toxic effect of aluminum leads to increase lipid peroxidation, oxidative stress and hepatotoxicity. In the current study, aluminum depleted GSH stores and reduced catalase and GSH-Px activities. These results are in harmony with other investigations.32 For example, aluminum induced hepatotoxicity was exacerbated by GSH depletion. In the current study, depletion of GSH stores can account for the inhibition of GSH-Px activity. In addition, high levels of peroxides may explain catalase activity inhibition.33 On the other hand, taurine can also function as a regulator of intracellular calcium homeostasis34 that can be disturbed due to aluminum toxicity. Taurine has been shown to protect against endothelial cell death by modulating intracellular calcium fluxes.35 Finally, taurine may ameliorate aluminum induced hepatic injury by enhancing the activities of endogenous antioxidants. Support for this concept comes from our results, which show that taurine produced a remarkable significant increase in hepatic GSH level and GSH-Px and catalase activities. This could be attributed to the role of taurine in maintaining a normal IGF-I level36 (Dawson et al., 1999) and its antioxidant action against lipid peroxidation, thus conserving the internal antioxidants system. The stimulatory effect of taurine on endogenous antioxidants was reported by others.37,38
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Together, the results of the present study demonstrate that administration of taurine has a therapeutic role in preventing cyclosporine-induced hepatotoxicity, possibly through its unique cytoprotective properties such as antioxidant activity. Accumulation of aluminum is the net consequence of uptake, biotransformation and elimination processes within an individual. Once aluminum is absorbed, it may be transformed into aluminumthionein or metallothionein. Although the half-life of aluminumthionein in the liver and kidney is not known exactly, it is many years.39 With continued retention, there is progressive accumulation in these tissues. The accumulated amount of aluminum in the tissue was effectively reduced by taurine. Taurine is a special amino acid, which possesses an amino group and a sulfonate group. These functional groups might bind with heavy metals, and then stimulated the excretion of such compounds. In this study, it was also found that the amount of aluminum in the feces of rats fed with taurine added was slightly increased. There is no evidence that taurine directly reduces the production of free radicals but it may well operate by binding aluminum which is then not absorbed or is more rapidly excreted. In other words it may act by reducing the overall bioavailability of aluminum or the intracellular availability of absorbed aluminum. Hence, dietary taurine may play a role to reduce the toxic effect of aluminum in the liver and kidney of rats. Conflicts of interest All authors have no Conflict of interest. Acknowledgement Y-H Yeh conducted the study design, experiment and wrote the manuscript. Y-T Lee and H-S Hsieh analyzed the data and statistical analysis. D-F Hwang performed data interpretation. All authors contributed to this study and reviewed the manuscript. References 1. Hewitt CD, Savory J, Wills MR. Aspects of aluminum toxicity. Clin Lab Med 1990;10:403–7. 2. Greyer JL, Powers CF. Assessment of exposure to parenteral and oral aluminum with and without citrate using a deferrioxamine test in rats. Toxicology 1992;76:119–32. 3. Fraga CG, Oteiza PI, Golub MS, Gershwin ME, Keen CL. Effect of aluminum on brain lipid peroxidation. Toxicol Lett 1990;51:213–9. 4. Savory J, Exley C, Forbes WF. Can the controversy of the role of aluminum in Alzheimer’s disease be resolved? What are the suggestive approaches to this controversy and methodological issues to be considered? J Toxicol Environ Health 1996;48:615–35. 5. Quartely B, Esselmont G, Taylor A, Dobrota M. Effect of oral aluminum citrate on short-term tissue distribution of aluminum. Food Chem Toxicol 1993;31:543–8. 6. Committee on Nutrition. Aluminum toxicity in infants and children. Pediatrics 1996;97:413–6. 7. Flaten TP, Alfrey AC, Birchall JD, Savory J, Yokel RA. Status and future concerns of clinical and environmental aluminum toxicology. J Toxicol Environ Health 1996;48:527–41. 8. Jeffery EH, Abreo K, Burgess E, Cannata J, Greger JL. Systemic aluminum toxicity: effects on bone, hematopoietic tissue, and kidney. J Toxicol Environ Health 1996;48:649–65.
9. Jacobsen JG, Smith LHJ. Biochemistry and physiology of taurine and taurine derivatives. Physiol Rev 1968;48:425–33. 10. Tokunaga H, Yoneda Y, Kuriyama K. Protective actions of taurine against streptozotocin-induced hyperglycemia. Biochem Pharmacol 1979;28:2807–18. 11. Hamaguchi T, Azuma J, Awata N, Ohta H, Takihara K, Harada H. Reduction of doxorubicin induced cardiotoxicity in mice by taurine. Res Commun Chem Pathol Pharmacol 1988;59:21–8. 12. Wang LC, Hwang DF, Jeng SS, Cheng HM. Effect of high dose of dietary taurine on toxicity of lead in rats. J Chin Agric Chem Soc 1997;35:612–8. 13. Hwang DF, Wang LC, Cheng HM. Effect of taurine on toxicity of copper in rats. Food Chem Toxicol 1998;36:239–46. 14. Hwang DF, Hour JL, Cheng HM. Effect of taurine on toxicity of oxidized fish oil in rats. Food Chem Toxicol 2000;38:585–96. 15. Yeh YH, Lee YT, Hsieh HS, Hwang DF. Effect of taurine on toxicity of vitamin A in rats. Food Chem 2008;106:260–8. 16. Yeh YH, Chen MH, Lee YT, Hsieh HS, Hwang DF. Effect of taurine on toxicity of oxidized cholesterol in rats. J Food Drug Anal 2008;16:74–82. 17. Yeh YH, Chen MH, Lee YT, Hsieh HS, Hwang DF. Effect of taurine on toxicity of oxidized cholesterol and oxidized fish oil in rats. J Food Drug Anal 2008;16: 76–85. 18. American Institute of Nutrition. Report of the American institute ad hoc committee on standards for nutritional studies. J Nutr 1977;107:1340–8. 19. Tatum VL, Changchit C, Chow CK. Measurement of malondialdehyde by high performance liquid chromatography with fluorescence detection. Lipids 1990;25:226–33. 20. Griffith OW. Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 1980;106:207–13. 21. Horwitz W. Official methods of analysis. 14th ed. Washington: AOAC; 1984. 22. Puri SC, Mullen K. Multiple comparisons. In: Hall GK, editor. Applied statistics for food and agricultural scientists. Boston: Medical; 1980. 23. Ronald L, Koretz MD. Chronic hepatitis: science and superstition. In: Gitnick G, editor. Current hepatology. Chicago: Mosby-Year; 1992. 24. Flora SJS, Dhawan M, Tandon SK. Effects of combined exposure to aluminum and ethanol on aluminum body burden and some hepatic and haematopoietic biochemical variables in the rat. Hum Exp Toxicol 1991;10:45–8. 25. Domingo JL, Llobet JM, Gomez M, Tomas JM, Corbella J. Nutritional and toxicological effects of short term ingestion of aluminum by rats. Res Commun Chem Pathol Pharmacol 1991;57:129–32. 26. Alfrey AC. Physiology of aluminum in man. In: Gitelman HJ, editor. Aluminum and health: a critcal review. New York: Marcel Dekker; 1989. p. 101–24. 27. Winship KA. Toxicity of aluminum: a historical review. Part 2. Adverse drug react. Toxicol Rev 1993;12:177–211. 28. Guyton C. Textbook of medical physiology. New York: Saunders; 1991. 29. Hicks JS, Hackett DS, Sprague GL. Toxicity and aluminum concentration in bone following dietary administration of two sodium aluminum phosphate formulations in rats. Food Chem Toxicol 1987;25:533–8. 30. Meister A. Selective modification of glutathione metabolism. Science 1983;22:472–8. 31. Gutteridg JMC. Lipid peroxidation and antioxidant as biomarkers of tissue damage. Clin Chem 1995;14:1819–28. 32. Al Khader A, Al Sulaiman M, Kishore PN, Morais C, Tariq M. Quinacrine attenuates cyclosporine-induced nephrotoxicity in rats. Transplantation 1996;62:427–35. 33. Ghadermarzi M, Moosavi-Movahedi AA. Determination of the kinetic parameters for the ‘‘suicide substrate’’ inactivation of bovine liver catalase by hydrogen peroxide. J Enzym Inhib 1996;10:167–75. 34. Huxtable RJ. Physiological actions of taurine. Physiol Rev 1992;72:101–63. 35. Wang JH, Redmond HP, Watson RWG, Condron C, Bouchier-Hayes D. The beneficial effect of taurine on the prevention of human endothelial cell death. Shock 1996;6:331–8. 36. Dawson JR, Liu S, Eppler B, Patterson T. Effects of dietary taurine supplementation or deprivation in aged male Fischer 344 rats. Mech Ageing Dev 1999;107: 73–91. 37. Erdem A, Gundogan NU, Usubutun A, Kiine K, Erdem RS, Kara A, et al. The protective effect of taurine against gentamicin-induced acute tubular necrosis in rats. Nephrol Dial Transplant 2000;15:1175–82. 38. Saad SY, Al-Rikabi AC. Protection effects of taurine supplementation against cisplatin-induced nephrotoxicity in rats. Chemotherapy 2002;48:42–8. 39. Goyer RA. Toxic effects of metals. In: Klaassen CD, editor. Casarett & Doull’s toxicology: the basic science of poisons. 5th ed. New York: McGraw-Hill; 1996.