- Email: [email protected]
Free oxygen radical-induced lipid peroxidation and antioxidant in infants receiving total parenteral nutrition
ARTICLE IN PRESS
Prostaglandins, Leukotrienes and Essential Fatty Acids 73 (2005) 99–102 www.elsevier.com/locate/plefa
Free oxygen radical-induced lipid peroxidation and antioxidant in infants receiving total parenteral nutrition Alev Hasanog˘lu, Nazan Dalgıc- , Leyla Tu¨mer, Yıldız Atalay, Gu¨lden Cinasal, Gu¨rsel Biberog˘lu, Neslihan Bukan, Cemalettin Aybar Faculty of Medicine, Department of Pediatrics, Gazi University, Ankara, Turkey Received 1 December 2004; accepted 24 April 2005
Abstract Objective: Increased oxygen-derived free radical activity has been reported during total parenteral nutrition (TPN) in infants particularly linked to the fat infusion. It is possible that partial enteral feeding can ameliorate some of the complications of TPN. By this study we aimed to investigate free radical formation and antioxidant activity in term and preterm infants during TPN and/or enteral feeding. Study design: We had 6 groups of term and preterm infants made up of 10 patients each. Group I had only enteral feeding, Group II enteral plus parenteral feeding, Group III only parenteral feeding. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), vitamin E and vitamin C levels were measured in all infants. Blood samples of infants receiving only TPN and TPN plus enteral feeding were measured on the 1st and 5th days, and 3 h after the end of lipid infusion. Results: There was no difference between the term and preterm infants in terms of MDA, SOD, vitamin C and E levels taken baseline and after parenteral, and enteral plus parenteral feeding on the 1st and 5th days. When 3 groups of both term and preterm infants were compared with each other none of the parameters showed a statistically significant difference. In addition, we compared baseline and 1st and 5th days of TPN therapy in both term and preterm infants fed only parenterally and enteral plus parenteral feedings. In term infants fed both parenterally and parenteral plus enterally, the MDA levels before TPN were significantly higher than that of the levels of patients on parenteral nutrition on the 5th day. On the 1st and 5th days of TPN therapy, the levels of vitamin C was significantly decreased, in term and preterm infants fed only parenterally, levels of vitamin E was increased, in term and preterm infants fed both parenterally and parenteral plus enterally. Also, when compared to their base line the SOD levels of the term infants detected on the 1st and 5th days were significantly high. Conclusion: Free radical production is increased by the administration of TPN and may be linked to its adverse effects. It may be assumed that long-term complications of preterm infants receiving TPN may be reduced by further strengthening the antioxidant capacities of the TPN solutions. r 2005 Elsevier Ltd. All rights reserved.
1. Introduction Total parenteral nutrition (TPN) is indicated for patients with pre-existing malnutrition or for those whose oral intake is anticipated to be inadequate for 7 days or more. This time period for very low birth weight (VLBW) infants is 2–3 days [1]. Total intravenous Corresponding author. Tel.: +90 312 241 0710; fax: +90 312 362 0581. E-mail address: [email protected] (N. Dalgıc- ).
0952-3278/$ - see front matter r 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.plefa.2005.04.015
alimentation may provide sufficient fluid, calories, amino acids, electrolytes, and vitamins to sustain the growth of VLBW infants [2]. An increase in free radical activity has been observed in newborns with various disorders. Free radical production is increased by the administration of TPN and may be linked to its adverse effects by damaging biologic macromolecules especially with polyunsaturated fatty acids in which free oxygen radical may induce lipid peroxidation, disturbing membrane function and leading to cell death. This is particularly disturbing in a newborn that is prone to
ARTICLE IN PRESS 100
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several diseases related to immature defence mechanisms against oxidative challenges. However, how the free radical production is influenced is still in question [3–5]. Furthermore, it is not clear whether the antioxidants in multivitamins help to protect parenteral nutrients against the hazards of oxidation [6]. The aim of this study is to establish whether there is a relationship between free radical activity and administration of TPN in term and preterm infants. In addition, the study sought whether enteral feeding during TPN affects free radical activity; vitamin C, added to TPN, protects parenteral nutrition against free radicals linked to the fat infusion.
(ELISA) using capture and detection antibodies from Serazyms Human Cu/Zn SOD Systems (Seruman, catalog no. E-002). Vitamin C and E levels were measured by spectrophotometric method [8,9]. Informed consent was obtained from the parents for each patient and the study was approved by the local hospital ethical committee. The data was stated as mean7standard deviation. The Mann–Whitney U-test was used for comparison of data between two independent groups of patients. The Wilcoxon signed-rank test was used for comparison of data in groups. The statistical analysis was performed using the SPSS software (SPSS 11.0, SPSS Inc., Chicago, and IL, USA). A P value o0.05 was considered statistically significant.
2. Materials and methods The study was conducted in Gazi University Department of Neonatology. A prospective longitudinal study was carried out in the Neonatology Unit of Gazi University Hospital. We had 6 groups of 10 term and preterm infants without infection. Group I had only enteral feeding, Group II enteral plus parenteral feeding, Group III only parenteral feeding. The two groups fed enterally were regarded as control groups. None of the patients received phototherapy for hyperbilirubinemia and vitamin C was added to TPN solution as an antioxidant. The TPN protocol of our clinic is shown in Table 1. The patients received 20% Intralipid at constant rates of 0.1 g/kg/h from a central or peripheral vein. Plasma MDA levels as indices of free radical activity, SOD, vitamin E and C levels as indices of antioxidant activity were measured in all 60 infants as baseline before starting therapy and on the 1st and 5th days and finally 3 h after the end of lipid infusion and stored at 70 1C. Plasma MDA levels were measured by the thiobutyric acid reaction products method [7]. SOD levels were analysed with enzyme-linked immunosorbent assay
3. Results The gestational ages of 60 babies were between 21 and 41 weeks (35.5074.11) and mean weight was 30447514.54 g (range 2000–4400). Oxidant and antioxidant parameters of the patients at base line, 1st- and 5th-day levels are shown in Table 2. There was no difference between the levels of MDA, SOD, vitamin C and E levels taken at baseline and after parenteral, and enteral plus parenteral feeding of the term and preterm infants (P40:05). When the 6 groups of both term and preterm infants were compared with each other none of the parameters showed a statistically significant difference (P40:05). In addition, we compared baseline, 1st- and 5th-day levels of all parameters in both term and preterm infants. In term infants fed both parenterally and parenteral plus enterally, the MDA levels before TPN were significantly higher than the levels of the 5th day of parenteral nutrition (Po0:05). When compared to the baseline levels, in term and preterm infants fed only parenterally, the levels of vitamin C were significantly decreased (Po0:05);
Table 1 TPN protocols of the patients 1 Day
2 Day
3 Day
4 Day
Amino acid Carbohydrate Lipid (20%) Vitamin C
g/kg/day g/kg/day g/kg/day mg/kg/day mg/day
0.5 10 0.5 Preterm: 25 Term: 80
1 12 1 Preterm: 25 Term: 80
1.5 12 1.5 Preterm: 25 Term: 80
2 14 2 Preterm: 25 Term: 80
Electrolytes
mEq/kg
Na and Cl: 3 K: 1
Na and Cl: 3 K: 1
Na and Cl: 3 K: 1
Na and Cl: 3 K: 1
Minerals
mg/dl
Calcium: 80 Phosphorus: 40
Calcium: 80 Phosphorus: 40
Calcium: 80 Phosphorus: 40
Calcium: 80 Phosphorus: 40
Volume
ml/kg
Preterm: 80–90 Term: 60–70
Preterm: 100–110 Term: 80–90
Preterm: 120–140 Term: 100–110
Preterm: 125–150 Term: 120–130
ARTICLE IN PRESS A. Hasanog˘lu et al. / Prostaglandins, Leukotrienes and Essential Fatty Acids 73 (2005) 99–102
101
Table 2 Oxidant and antioxidant parameters of the patients at baseline, 1st- and 5th-day levels Baseline levels
1 Day
5 Day
Group I MDA (nm/ml) SOD (ng/ml) Vitamin E (mg/l) Vitamin C (mg/dl)
42.12712.51 26.9476.71 10.1378.76 0.9370.47
— — — —
— — — —
Group II MDA (nm/ml) SOD (ng/ml) VI˙TAMIN E (mg/l) VI˙TAMIN C (mg/dl)
50.49714.26** 21.7579.84 9.8974.41*,** 0.5970.21
41.36722.05 26.22711.72 13.9074.36 0.6770.65
36.59716.46 27.1678.19 15.9877.85 0.6770.56
Group III MDA (nm/ml) SOD (ng/ml) Vitamin E (mg/l) Vitamin C (mg/dl)
57.60727.35** 15.50711.34*,** 7.9272.06*,** 0.6370.16*,**
37.42721.54 22.51716.27 10.9374.11** 0.4670.15
30.73710.01 26.7778.45 13.1275.94 0.4470.13
Group IV MDA (nm/ml) SOD (ng/ml) Vitamin E (mg/l) Vitamin C (mg/dl)
55.29720.75 20.59711.24 13.5377.04 0.7670.34
— — — —
— — — —
Group V MDA (nm/ml) SOD (ng/ml) Vitamin E (mg/l) Vitamin C (mg/dl)
53.26717.83 21.95710.51 9.1376.5*,** 0.6270.31
46.83719.17 23.2778.99 12.5775.18** 0.6270.37
40.49718.57 26.4677.13 16.7975.25 0.6670.44
Group VI MDA (nm/ml) SOD (ng/ml) Vitamin E (mg/l) Vitamin C (mg/dl)
58.18714.26 25.79713.84 9.9675.80*,** 0.7670.34*,**
51.82723.81 27712.43 16.6577.27 0.5570.11
43.74730.88 33.0776.06 18.8476.63 0.4970.12
Note: Data expressed as mean value7SD *Significantly different from level of 1st day (Po0:05). **Significantly different from level of 5th day (Po0:05).
levels of vitamin E were increased in term and preterm infants fed both parenterally (Po0:05) and parenteral plus enterally (Po0:05) on the 1st and 5th days of TPN therapy. Also, the SOD levels of the parenterally fed term infants at the 1st and 5th days when compared to those of their baseline levels were significantly high (Po0:05). There was no significant difference between other oxidant and antioxidant parameters in the same groups. The level of MDA in patients on TPN was not changed by partial enteral feeding (P40:05).
4. Discussion In neonatology free radical mediated reactions as mediators of tissue injures are implicated in the pathogenesis of various complications such as bronchopulmonary dysplasia, retinopathy of prematurity and
necrotising enterocolitis [10]. Evidence of free radical activity has been correlated with an adverse outcome especially in VLBW premature infants [11]. Parenteral nutrition allows us to meet a newborn’s requirements for growth and development when the newborn’s size and condition precludes enteral feeding. However, an increase in the formation of free radicals has been found in neonates receiving TPN [12]. Some complications of TPN including biliary stasis, reduced immune function and intestinal mucosal changes are known to respond to small amounts of enteral nutrition. Controversies exist about the fact whether partial nutrition ameliorates free radical production and there is also no data about the affects of vitamins on free radical production during parenteral nutrition [3,6,13]. In our study free radical activity was assessed by measuring plasma MDA concentrations. MDA is formed from the breakdown of lipid peroxides and is one of the most commonly used indices of free radical
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activity. The decrease in MDA levels during parenteral nutrition may be due to the inhibitory effect of vitamin C that was added to parenteral nutrition solution as an antioxidant. This result is consistent with the previous study of Pitkanen et al., which showed that SOD or vitamin C inhibited MDA production [14]. The decreasing levels of vitamin C found on the 1st and 5th days of TPN therapy when compared to the base line were due to it being used as an antioxidant. The previous reports show that premature infants with reduced levels of SOD, vitamin E, catalase and glutathione peroxidase have an insufficient antioxidant capacity, and are thought to be more prone to free radical damage [14,15]. However, in our study similar to the Chan et al.’s result [16], we could not find any differences in SOD, vitamin E and C levels between mature and premature groups. This may be due to our premature patient’s considerably higher gestational ages (32.1673.25) supplied with sufficient amount of antioxidants. Our finding that the early minimal enteral nutrition during TPN infusion did not reduce the free radical production was inconsistent with some of the previous studies [3,14,17]. Besides having many other beneficial effects, add-on early minimal enteral nutrition had no effect on free radical production. By a limited number of patients in our study groups we further showed that TPN leads to oxidative damage by free radical production; vitamin C when added ameliorates this effect. In order to have firm conclusion, double blind randomised controlled studies with greater number of patients are needed. References [1] J. MacFie, Enteral versus parenteral nutrition, Br. J. Surg. 87 (2000) 1121–1122. [2] B.J. Stoll, R.M. Kliegman, The high-risk infant, in: R.E. Behrman, R.M. Kliegman, H.B. Jenson (Eds.), Nelson Textbook of Pediatrics, 17th ed., Churchill-Livingstone, New York, 2004, pp. 547–559.
[3] R. Basu, D.P.R. Muller, E. Papp, et al., Free radical formation in infants: the effect of critical illness, parenteral nutrition, and enteral feeding, J. Pediatr. Surg. 34 (1999) 1091–1095. [4] H. Hayashibe, K. Asayama, K. Dobashi, K. Kato, Prenatal development of antioxidant enzymes in rat lung, kidney, and heart: marked increase in immunoreactive superoxide dismutase, glutathione peroxidase, and catalase in the kidney, Pediatr. Res. 27 (1990) 472–475. [5] E. Varsıla, O. Pıtkanen, M. Hallman, S. Andersson, Immaturity dependent free radical activity in premature infants, Pediatr. Res. 36 (1997) 55–59. [6] J.C. Lavoie, S. Belanger, M. Spalinger, P. Chessex, Admixture of a multivitamin preparation to parenteral nutrition: the major contributor to in vitro generation of peroxides, Pediatrics 99 (1997) E6. [7] K. Yagi, A simple fluorometric assay for lipoperoxide in blood plasma, Biochem. Med. 15 (1976) 212–216. [8] D.B. Mc Cormic, Methods for the determination of ascorbic acid, in: W. Nobert, X. Tietz (Eds.), Textbook of Clinical Chemistry, WB Saunders Company, 1st Press, Philadelphia, PA, 1986, pp. 960–962. [9] G. Rindi, A rapid calorimetric method for determination of tocopherol and tocopheryl acetate in plasma, Int. Z. Vitaminforsch. Beih. 28 (1958) 225–234. [10] O.D. Saugstad, Mechanisms of tissue injury by oxygen radicals: implications for neonatal disease, Acta. Paediatr. 85 (1996) 1–4. [11] T.E. Inder, B.A. Darlow, K.B. Sluis, et al., The correlation of elevated levels of an index of lipid peroxidation (MDA-TBA) with adverse outcome in the very low birth infant, Acta Paediatr. 85 (1996) 1116–1122. [12] J.R. Wesley, A.G. Coran, Intravenous nutrition for pediatric patient, Semin. Pediatr. Surg. 3 (1992) 212–230. [13] Y. Okada, N. Klein, H.K. van Saene, A. Pierro, Small volumes of enteral feedings normalise immune function in infants receiving parenteral nutrition, J. Pediatr. Surg. 33 (1998) 16–19. [14] O. Pıtkanen, M. Hallman, S. Andersson, Generation of free radicals in lipid Emulsion used in parenteral nutrition, Pediatr. Res. 29 (1991) 56–59. [15] G. Baydas-, F. Karatas-, M.F. Gursu, et al., Antioxidant vitamin levels in term and preterm infants and their relation to maternal vitamin status, Arch. Med. Res. 33 (2002) 276–280. [16] D.K. Chan, M.S. Lim, S.H. Choo, I.K. Tan, Vitamin E status of infants at birth, J. Perinat. Med. 27 (5) (1999) 395–398. [17] R. Basu, D.P.R. Muller, S. Eaton, I. Merryweather, A. Pierro, Lipid peroxidation can be reduced in infants on TPN by promoting fat utilization, J. Pediatr. Surg. 34 (1999) 255–259.
Prostaglandins, Leukotrienes and Essential Fatty Acids 73 (2005) 99–102 www.elsevier.com/locate/plefa
Free oxygen radical-induced lipid peroxidation and antioxidant in infants receiving total parenteral nutrition Alev Hasanog˘lu, Nazan Dalgıc- , Leyla Tu¨mer, Yıldız Atalay, Gu¨lden Cinasal, Gu¨rsel Biberog˘lu, Neslihan Bukan, Cemalettin Aybar Faculty of Medicine, Department of Pediatrics, Gazi University, Ankara, Turkey Received 1 December 2004; accepted 24 April 2005
Abstract Objective: Increased oxygen-derived free radical activity has been reported during total parenteral nutrition (TPN) in infants particularly linked to the fat infusion. It is possible that partial enteral feeding can ameliorate some of the complications of TPN. By this study we aimed to investigate free radical formation and antioxidant activity in term and preterm infants during TPN and/or enteral feeding. Study design: We had 6 groups of term and preterm infants made up of 10 patients each. Group I had only enteral feeding, Group II enteral plus parenteral feeding, Group III only parenteral feeding. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), vitamin E and vitamin C levels were measured in all infants. Blood samples of infants receiving only TPN and TPN plus enteral feeding were measured on the 1st and 5th days, and 3 h after the end of lipid infusion. Results: There was no difference between the term and preterm infants in terms of MDA, SOD, vitamin C and E levels taken baseline and after parenteral, and enteral plus parenteral feeding on the 1st and 5th days. When 3 groups of both term and preterm infants were compared with each other none of the parameters showed a statistically significant difference. In addition, we compared baseline and 1st and 5th days of TPN therapy in both term and preterm infants fed only parenterally and enteral plus parenteral feedings. In term infants fed both parenterally and parenteral plus enterally, the MDA levels before TPN were significantly higher than that of the levels of patients on parenteral nutrition on the 5th day. On the 1st and 5th days of TPN therapy, the levels of vitamin C was significantly decreased, in term and preterm infants fed only parenterally, levels of vitamin E was increased, in term and preterm infants fed both parenterally and parenteral plus enterally. Also, when compared to their base line the SOD levels of the term infants detected on the 1st and 5th days were significantly high. Conclusion: Free radical production is increased by the administration of TPN and may be linked to its adverse effects. It may be assumed that long-term complications of preterm infants receiving TPN may be reduced by further strengthening the antioxidant capacities of the TPN solutions. r 2005 Elsevier Ltd. All rights reserved.
1. Introduction Total parenteral nutrition (TPN) is indicated for patients with pre-existing malnutrition or for those whose oral intake is anticipated to be inadequate for 7 days or more. This time period for very low birth weight (VLBW) infants is 2–3 days [1]. Total intravenous Corresponding author. Tel.: +90 312 241 0710; fax: +90 312 362 0581. E-mail address: [email protected] (N. Dalgıc- ).
0952-3278/$ - see front matter r 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.plefa.2005.04.015
alimentation may provide sufficient fluid, calories, amino acids, electrolytes, and vitamins to sustain the growth of VLBW infants [2]. An increase in free radical activity has been observed in newborns with various disorders. Free radical production is increased by the administration of TPN and may be linked to its adverse effects by damaging biologic macromolecules especially with polyunsaturated fatty acids in which free oxygen radical may induce lipid peroxidation, disturbing membrane function and leading to cell death. This is particularly disturbing in a newborn that is prone to
ARTICLE IN PRESS 100
A. Hasanog˘lu et al. / Prostaglandins, Leukotrienes and Essential Fatty Acids 73 (2005) 99–102
several diseases related to immature defence mechanisms against oxidative challenges. However, how the free radical production is influenced is still in question [3–5]. Furthermore, it is not clear whether the antioxidants in multivitamins help to protect parenteral nutrients against the hazards of oxidation [6]. The aim of this study is to establish whether there is a relationship between free radical activity and administration of TPN in term and preterm infants. In addition, the study sought whether enteral feeding during TPN affects free radical activity; vitamin C, added to TPN, protects parenteral nutrition against free radicals linked to the fat infusion.
(ELISA) using capture and detection antibodies from Serazyms Human Cu/Zn SOD Systems (Seruman, catalog no. E-002). Vitamin C and E levels were measured by spectrophotometric method [8,9]. Informed consent was obtained from the parents for each patient and the study was approved by the local hospital ethical committee. The data was stated as mean7standard deviation. The Mann–Whitney U-test was used for comparison of data between two independent groups of patients. The Wilcoxon signed-rank test was used for comparison of data in groups. The statistical analysis was performed using the SPSS software (SPSS 11.0, SPSS Inc., Chicago, and IL, USA). A P value o0.05 was considered statistically significant.
2. Materials and methods The study was conducted in Gazi University Department of Neonatology. A prospective longitudinal study was carried out in the Neonatology Unit of Gazi University Hospital. We had 6 groups of 10 term and preterm infants without infection. Group I had only enteral feeding, Group II enteral plus parenteral feeding, Group III only parenteral feeding. The two groups fed enterally were regarded as control groups. None of the patients received phototherapy for hyperbilirubinemia and vitamin C was added to TPN solution as an antioxidant. The TPN protocol of our clinic is shown in Table 1. The patients received 20% Intralipid at constant rates of 0.1 g/kg/h from a central or peripheral vein. Plasma MDA levels as indices of free radical activity, SOD, vitamin E and C levels as indices of antioxidant activity were measured in all 60 infants as baseline before starting therapy and on the 1st and 5th days and finally 3 h after the end of lipid infusion and stored at 70 1C. Plasma MDA levels were measured by the thiobutyric acid reaction products method [7]. SOD levels were analysed with enzyme-linked immunosorbent assay
3. Results The gestational ages of 60 babies were between 21 and 41 weeks (35.5074.11) and mean weight was 30447514.54 g (range 2000–4400). Oxidant and antioxidant parameters of the patients at base line, 1st- and 5th-day levels are shown in Table 2. There was no difference between the levels of MDA, SOD, vitamin C and E levels taken at baseline and after parenteral, and enteral plus parenteral feeding of the term and preterm infants (P40:05). When the 6 groups of both term and preterm infants were compared with each other none of the parameters showed a statistically significant difference (P40:05). In addition, we compared baseline, 1st- and 5th-day levels of all parameters in both term and preterm infants. In term infants fed both parenterally and parenteral plus enterally, the MDA levels before TPN were significantly higher than the levels of the 5th day of parenteral nutrition (Po0:05). When compared to the baseline levels, in term and preterm infants fed only parenterally, the levels of vitamin C were significantly decreased (Po0:05);
Table 1 TPN protocols of the patients 1 Day
2 Day
3 Day
4 Day
Amino acid Carbohydrate Lipid (20%) Vitamin C
g/kg/day g/kg/day g/kg/day mg/kg/day mg/day
0.5 10 0.5 Preterm: 25 Term: 80
1 12 1 Preterm: 25 Term: 80
1.5 12 1.5 Preterm: 25 Term: 80
2 14 2 Preterm: 25 Term: 80
Electrolytes
mEq/kg
Na and Cl: 3 K: 1
Na and Cl: 3 K: 1
Na and Cl: 3 K: 1
Na and Cl: 3 K: 1
Minerals
mg/dl
Calcium: 80 Phosphorus: 40
Calcium: 80 Phosphorus: 40
Calcium: 80 Phosphorus: 40
Calcium: 80 Phosphorus: 40
Volume
ml/kg
Preterm: 80–90 Term: 60–70
Preterm: 100–110 Term: 80–90
Preterm: 120–140 Term: 100–110
Preterm: 125–150 Term: 120–130
ARTICLE IN PRESS A. Hasanog˘lu et al. / Prostaglandins, Leukotrienes and Essential Fatty Acids 73 (2005) 99–102
101
Table 2 Oxidant and antioxidant parameters of the patients at baseline, 1st- and 5th-day levels Baseline levels
1 Day
5 Day
Group I MDA (nm/ml) SOD (ng/ml) Vitamin E (mg/l) Vitamin C (mg/dl)
42.12712.51 26.9476.71 10.1378.76 0.9370.47
— — — —
— — — —
Group II MDA (nm/ml) SOD (ng/ml) VI˙TAMIN E (mg/l) VI˙TAMIN C (mg/dl)
50.49714.26** 21.7579.84 9.8974.41*,** 0.5970.21
41.36722.05 26.22711.72 13.9074.36 0.6770.65
36.59716.46 27.1678.19 15.9877.85 0.6770.56
Group III MDA (nm/ml) SOD (ng/ml) Vitamin E (mg/l) Vitamin C (mg/dl)
57.60727.35** 15.50711.34*,** 7.9272.06*,** 0.6370.16*,**
37.42721.54 22.51716.27 10.9374.11** 0.4670.15
30.73710.01 26.7778.45 13.1275.94 0.4470.13
Group IV MDA (nm/ml) SOD (ng/ml) Vitamin E (mg/l) Vitamin C (mg/dl)
55.29720.75 20.59711.24 13.5377.04 0.7670.34
— — — —
— — — —
Group V MDA (nm/ml) SOD (ng/ml) Vitamin E (mg/l) Vitamin C (mg/dl)
53.26717.83 21.95710.51 9.1376.5*,** 0.6270.31
46.83719.17 23.2778.99 12.5775.18** 0.6270.37
40.49718.57 26.4677.13 16.7975.25 0.6670.44
Group VI MDA (nm/ml) SOD (ng/ml) Vitamin E (mg/l) Vitamin C (mg/dl)
58.18714.26 25.79713.84 9.9675.80*,** 0.7670.34*,**
51.82723.81 27712.43 16.6577.27 0.5570.11
43.74730.88 33.0776.06 18.8476.63 0.4970.12
Note: Data expressed as mean value7SD *Significantly different from level of 1st day (Po0:05). **Significantly different from level of 5th day (Po0:05).
levels of vitamin E were increased in term and preterm infants fed both parenterally (Po0:05) and parenteral plus enterally (Po0:05) on the 1st and 5th days of TPN therapy. Also, the SOD levels of the parenterally fed term infants at the 1st and 5th days when compared to those of their baseline levels were significantly high (Po0:05). There was no significant difference between other oxidant and antioxidant parameters in the same groups. The level of MDA in patients on TPN was not changed by partial enteral feeding (P40:05).
4. Discussion In neonatology free radical mediated reactions as mediators of tissue injures are implicated in the pathogenesis of various complications such as bronchopulmonary dysplasia, retinopathy of prematurity and
necrotising enterocolitis [10]. Evidence of free radical activity has been correlated with an adverse outcome especially in VLBW premature infants [11]. Parenteral nutrition allows us to meet a newborn’s requirements for growth and development when the newborn’s size and condition precludes enteral feeding. However, an increase in the formation of free radicals has been found in neonates receiving TPN [12]. Some complications of TPN including biliary stasis, reduced immune function and intestinal mucosal changes are known to respond to small amounts of enteral nutrition. Controversies exist about the fact whether partial nutrition ameliorates free radical production and there is also no data about the affects of vitamins on free radical production during parenteral nutrition [3,6,13]. In our study free radical activity was assessed by measuring plasma MDA concentrations. MDA is formed from the breakdown of lipid peroxides and is one of the most commonly used indices of free radical
ARTICLE IN PRESS 102
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activity. The decrease in MDA levels during parenteral nutrition may be due to the inhibitory effect of vitamin C that was added to parenteral nutrition solution as an antioxidant. This result is consistent with the previous study of Pitkanen et al., which showed that SOD or vitamin C inhibited MDA production [14]. The decreasing levels of vitamin C found on the 1st and 5th days of TPN therapy when compared to the base line were due to it being used as an antioxidant. The previous reports show that premature infants with reduced levels of SOD, vitamin E, catalase and glutathione peroxidase have an insufficient antioxidant capacity, and are thought to be more prone to free radical damage [14,15]. However, in our study similar to the Chan et al.’s result [16], we could not find any differences in SOD, vitamin E and C levels between mature and premature groups. This may be due to our premature patient’s considerably higher gestational ages (32.1673.25) supplied with sufficient amount of antioxidants. Our finding that the early minimal enteral nutrition during TPN infusion did not reduce the free radical production was inconsistent with some of the previous studies [3,14,17]. Besides having many other beneficial effects, add-on early minimal enteral nutrition had no effect on free radical production. By a limited number of patients in our study groups we further showed that TPN leads to oxidative damage by free radical production; vitamin C when added ameliorates this effect. In order to have firm conclusion, double blind randomised controlled studies with greater number of patients are needed. References [1] J. MacFie, Enteral versus parenteral nutrition, Br. J. Surg. 87 (2000) 1121–1122. [2] B.J. Stoll, R.M. Kliegman, The high-risk infant, in: R.E. Behrman, R.M. Kliegman, H.B. Jenson (Eds.), Nelson Textbook of Pediatrics, 17th ed., Churchill-Livingstone, New York, 2004, pp. 547–559.
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