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BDE-99 exposed rats: An assessment of the hormonal status and biochemical parameters in adult animals
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Abstracts / Toxicology Letters 196S (2010) S37–S351
P103-010 Possible hypotheses on the discrepancy between the literature data on the effects of ambient air pollution and pregnant women and birth outcomes G. Polichetti 1 , K. Grigoropoulos 2 , R. Polichetti 1 , D. Capone 1 , I. Montoro 1 , C. Attianese 1 , M. Russo 3 , I. Kadilli 1 , A. Nunziata 4 , A. Gentile 1 1 Department of Neurosciences, Unit of Clinical Pharmacology, School of Medicine, Federico II, University of Naples, Italy, 2 University of Patras, Geology and Environment, 26500, Patras, Greece, 3 Department of Neurosciences, Unit of Physiology, School of Medicine, Federico II, University of Naples, Italy, 4 Consultant, Via Mar Nero 31, 00040 Pomezia, Italy
We have extensive evidences that ambient air pollution affects human health and several studies in the last decades have been focused on the effects of air pollution on adult morbidity and mortality for cardiovascular and respiratory diseases. Only in recent years scientific community have focused the studies on the possible adverse effects of ambient air pollutants on pregnant women and birth outcomes. The study of birth outcomes is an important emerging field of environmental epidemiology and should have an important significance for both social and public health. The literature data in this matter are in conflict. In fact, several epidemiological studies have founded associations between ambient air pollutants (CO, O3 , NO2 , SO2 , PM10 and PM2.5) and pregnancy outcomes and birth defects (low birth weight, very low birth weight, preterm birth, intrauterine growth restriction and intrauterine mortality), but in many other studies these associations are not demonstrated. Furthermore the possible mechanisms of these effects have been only hypothesized and have not yet been clarified. We have hypothesized that the possible discrepancies between these epidemiological studies depend on the short or longterm exposure to ambient air pollutants, on trimester of exposure in pregnant women (first, second or third) and on particular internal composition of PM10 and PM2.5. In fact, the PM can spread from the lungs to the circulatory system and interact with the foetus, and its particular internal composition can give an account of the presence or absence of particular diseases in the foetus. In conclusion we suggest further studies on the short and long-term exposure to ambient air pollutants, on the trimester of pregnancy and on the effects of PM analysing its particular internal composition. doi:10.1016/j.toxlet.2010.03.220
ysis. Our results show that the CSSP condensate (0–20 g/ml) has similar dose-dependent estrogenic effects on ERa and ERb in the absence of estradiol (E2). Co-expression of AhR does not affect the estrogenic effects of CSSP. The estrogenicity of CSSP at 20 g/ml is comparable to that exhibited by 1 nM E2 in all the cell lines examined. Cotreatment of cells with CSSP and E2 leads to an additive estrogenic response in ERa+ cells, whereas the cotreatement does not alter or improve E2-induced ERb activation. To check whether the estrogenic activity of CSSP is mediated through ERa and ERb, a pure antiestrogen compound ICI 182780 is used to block the binding of ligands to these ERs. ICI 182780 at 10 nM can efficiently prevent E2 from activating ERa and ERb. This concentration of ICI 182780 does not affect the estrogenic effect of CSSP on ERa regardless of the presence and absence of E2, but it reduces the estrogenic effect on ERb. These results suggest that (1) CSSP can activate ERa and ERb by a mechanism independent of ligand binding, and (2) CSSP contains some components that can act as ERb ligands. doi:10.1016/j.toxlet.2010.03.221
P103-012 Bisphenol A-induced aromatase activation is mediated by camp response element activation in rat testicular Leydig cells E.H. Han 1 , J.Y. Kim 1 , K.Y. Lee 2 , H.G. Jeong 1 1
Chungnam National University, Republic of Korea, 2 Chonnam National University, Republic of Korea Bisphenol A (4,4 -dihydroxy-2,2-diphenylpropane; BPA) is an endocrine disruptor that affects the reproductive health of wildlife and possibly of humans. We evaluated the effect of BPA on aromatase expression in rat testicular Leydig cells. BPA induced a time- and concentration-dependent increase in aromatase protein expression in rat testicular Leydig R2C cells. It also increased aromatase gene expression and its enzyme and promoter activity, but reduced testosterone synthesis; the production of prostaglandin E2 (PGE2), and the gene expression of PGE2 (EP2 and EP4) receptors; induced the activation of cyclic adenosine monophosphate (cAMP) response element (CRE) and CREB binding; and increased the phosphorylation of protein kinase A (PKA), Akt, and mitogenactivated protein (MAP) kinase signaling pathways. Taken together, these results suggest that BPA increases aromatase activity mediated by the CRE, PKA, Akt, and MAP kinase signaling pathways in rat testicular Leydig cells. doi:10.1016/j.toxlet.2010.03.222
P103-011 Estrognic effect of second-hand cigarette smoke in lung cancer cell lines expressing different receptor phenotypes L.C. Kuo, S.F. Lin, L.A. Li National Health Research Institutes/Division of Environmental Health & Occupational Medicine, Taiwan Increasing evidence shows that women are more vulnerable to lung cancer than men, suggesting that estrogen plays a role in the pathology of this cancer. Cigarette smoke contains enormous estrogen-like polycyclic aromatic hydrocarbons that may alter the activity of estrogen receptors (ERs) directly or indirectly through aryl hydrocarbon receptor (AhR). Here we examine estrogenic and antiestrogenic effects of a condensate of cigarette side-stream particulates (CSSP) in lung cancer cell lines that are engineered to exhibit different ER/AhR phenotypes by reporter transfection anal-
P103-013 BDE-99 exposed rats: An assessment of the hormonal status and biochemical parameters in adult animals V. Alonso, M. Bellés, M.L. Albina, V. Linares, A. Pujol, D. Sánchez, J.L. Domingo School of Medicine, IISPV “Universitat Rovira i Virgili”, Spain Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants. Among them, the 2,2 ,4,4 ,5-pentabromodiphenyl ether (BDE-99) is one of the most persistent congeners in wildlife and humans. Although developmental neurotoxicity of PBDEs has been investigated, little is known about their toxicological effects in adulthood. The aim of this study was to assess in adult rats the effects of BDE-99 on the hormonal status and biochemical parameters. Animals (10 per group) were given by gavage a single dose of
Abstracts / Toxicology Letters 196S (2010) S37–S351
0, 0.6, or 1.2 mg BDE-99/kg of body weight. After 45 days, urine and blood samples were collected for biochemical analysis, including the determination of oxidative stress (OS) markers. In urine, lactate dehydrogenase (LDH), ␥-glutamil-transferase (GGT), and N-acetil-d-glucosaminidase (NAG) activities significantly decreased at 1.2 mg BDE-99/kg. The urinary excretion of total protein significantly increased at both BDE-99 doses. In blood, BDE-99 caused an increase in glutamyl pyruvic transaminase (GPT), glutamyl oxaloacetic transaminase (GOT), and alkaline phosphatase (ALP) activities at 1.2 mg/kg. In turn, a significant decrease in uric acid levels was observed in all BDE-99 treated animals. The analysis of blood OS markers revealed a significant increase in superoxide dismutase (SOD) activity, while glutathione reductase (GR) activity significantly decreased in both BDE-99 treated groups. In urine, isoprostane levels increased following BDE-99 exposure. On the other hand, the serum levels of testosterone significantly decreased in rats treated with BDE-99. Progesterone levels significantly decreased at 1.2 mg BDE-99/kg. These results demonstrate that exposure of adult rats to BDE-99 interacts with the hormonal response. Moreover, alterations in biochemical parameters showed signs of renal and hepatic toxicity. Further investigations on the mechanism of action of BDE-99 are clearly necessary in order to establish the potential human health risks of this pollutant. doi:10.1016/j.toxlet.2010.03.223
P103-014 Concentrations of urinary phthalates metabolites in Mexican women with and without diabetes K. Svensson 1 , R.U. Hernández-Ramírez 2 , A. Burguette 2 , M. Cebrian 3 , L. Claudio 4 , L. López-Carrillo 2 1
Graduate School of Public Health, University of Puerto Rico, United States, 2 National Institute of Public Health, Cuernavaca, Morelos, Mexico, 3 Sección Externa de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico, 4 Department of Community and Preventive Medicine, Mount Sinai School of Medicine, NY, United States
Background: Phthalates are ubiquitous industrial chemicals used as plasticizers in plastics made of polyvinyl chloride (PVC) to confer flexibility and durability. Phthalates have been associated with several adverse health effects, and recently it has been proposed that exposure to phthalates, could have an effect on metabolic homeostasis. Therefore, this exploratory cross-sectional study evaluated the possible association between phthalate exposure and self-reported diabetes among adult Mexican women. Methods: As part of an on-going case-control study only controls were selected, which constituted 221 healthy women matched by age (±5 years) and place of residence with the cases. Women with diabetes were identified by self-report and a urine sample of each woman was collected to measure the urinary concentrations of nine phthalate metabolites. The association between phthalates metabolites and diabetes were assessed by logistic regression models. Results: The exposure levels of phthalate metabolites varied by diabetes status. Participants with diabetes had significantly higher levels of the metabolites MEHHP, MEOHP, MECPP and the sum of DEHP metabolites (DEHP), but lower levels of MBzP, compared to participants without diabetes (p-value <0.05). Moreover, two associations remained marginally significant (MEHHP: p for trend = 0.063, and MEOHP: p for trend = 0.079; respectively), even after adjusting for age and education. Conclusions: This exploratory cross-sectional study found significant association between phthalate metabolites and diabetes status. Phthalate exposure could have an effect on
S57
the human metabolism and also play an important role on the prevalence of diabetes. doi:10.1016/j.toxlet.2010.03.224
P103-015 Nanoparticle-rich diesel exhaust-disrupted testosterone biosynthesis and metabolism might be mediated by growth hormone D.H. Ramdhan 1 , Y. Ito 2 , Y. Yanagiba 1 , N. Yamagishi 1 , Y. Hayashi 1 , A.K. Suzuki 3 , T. Nakajima 1 1
Nagoya University Graduate School of Medicine, Japan, 2 Nagoya City University Graduate School of Medicine, Japan, 3 Japan National Institute for Environmental Studies, Research Center for Environmental Risk, Japan
Diesel exhaust particles (DEPs), which are ubiquitously present air pollutants resulting from increased use of vehicles, have hazardous effects on human health, as reported in numerous epidemiological studies showing associations between DEP exposure and cardiovascular disease, allergic rhinitis, pulmonary cancer, and disruption of reproductive function. DEP contains amounts of small particles ranging from nanoparticles (NP) to coarse particles. This suggests that much more attention should be paid to the adverse effects of NPs (NR-DE) included in DEPs. We previously reported that exposure to low (22.5 ± 0.2 nm in diameter, 15.4 ± 1.0 g/m3 in mass weight, 2.27 × 105 /cm3 in mean number concentration), and medium (26.1 ± 0.5 nm, 36.4 ± 1.2 g/m3 , 5.11 × 105 /cm3 ) concentrations of nanoparticle-rich diesel exhaust (NR-DE) for one and two months (5 h/day, 5 days/week) significantly increased plasma testosterone in male Fischer 344 rats, whereas exposure to a high concentration (27.1 ± 0.5 nm, 168.8 ± 2.7g/m3 , 1.36 × 106 /cm3 ) did not. The present study attempts to clarify the mechanism of this elevation. Low and medium exposures to NR-DE for one and two months significantly increased steroidogenic acute regulatory protein (StAR)- and cytochrome P450 side-chain cleavage (P450scc)-mRNA and their protein expressions in the testis of rats, in which the elevation pattern was very similar to that of plasma testosterone levels. Interestingly, both exposure levels for one month significantly increased growth hormone (GH) receptor expression in the testis, and low exposure also increased testicular insulin-like growth factor I-mRNA levels and hepatic microsomal cytochrome P450 2C11-mRNA and their protein levels in rats. These two factors are thought to be related to growth hormone secretion. Disruption of testosterone biosynthesis by NR-DE exposure may be a mode of action for reproductive toxicity, which may, in part, be regulated by increasing StAR and P450scc expressions via GH signalling. doi:10.1016/j.toxlet.2010.03.225
P103-016 Flavone regulation of steroidogenic CYP11B1 and CYP11B2 genes L.C. Cheng, J.R. Lin, L.A. Li Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan Recent years there are growing interests in flavonoids, a group of polyphenolic compounds present abundantly in plants, because of their pharmacological potential in anti-inflammation, antiox-
Abstracts / Toxicology Letters 196S (2010) S37–S351
P103-010 Possible hypotheses on the discrepancy between the literature data on the effects of ambient air pollution and pregnant women and birth outcomes G. Polichetti 1 , K. Grigoropoulos 2 , R. Polichetti 1 , D. Capone 1 , I. Montoro 1 , C. Attianese 1 , M. Russo 3 , I. Kadilli 1 , A. Nunziata 4 , A. Gentile 1 1 Department of Neurosciences, Unit of Clinical Pharmacology, School of Medicine, Federico II, University of Naples, Italy, 2 University of Patras, Geology and Environment, 26500, Patras, Greece, 3 Department of Neurosciences, Unit of Physiology, School of Medicine, Federico II, University of Naples, Italy, 4 Consultant, Via Mar Nero 31, 00040 Pomezia, Italy
We have extensive evidences that ambient air pollution affects human health and several studies in the last decades have been focused on the effects of air pollution on adult morbidity and mortality for cardiovascular and respiratory diseases. Only in recent years scientific community have focused the studies on the possible adverse effects of ambient air pollutants on pregnant women and birth outcomes. The study of birth outcomes is an important emerging field of environmental epidemiology and should have an important significance for both social and public health. The literature data in this matter are in conflict. In fact, several epidemiological studies have founded associations between ambient air pollutants (CO, O3 , NO2 , SO2 , PM10 and PM2.5) and pregnancy outcomes and birth defects (low birth weight, very low birth weight, preterm birth, intrauterine growth restriction and intrauterine mortality), but in many other studies these associations are not demonstrated. Furthermore the possible mechanisms of these effects have been only hypothesized and have not yet been clarified. We have hypothesized that the possible discrepancies between these epidemiological studies depend on the short or longterm exposure to ambient air pollutants, on trimester of exposure in pregnant women (first, second or third) and on particular internal composition of PM10 and PM2.5. In fact, the PM can spread from the lungs to the circulatory system and interact with the foetus, and its particular internal composition can give an account of the presence or absence of particular diseases in the foetus. In conclusion we suggest further studies on the short and long-term exposure to ambient air pollutants, on the trimester of pregnancy and on the effects of PM analysing its particular internal composition. doi:10.1016/j.toxlet.2010.03.220
ysis. Our results show that the CSSP condensate (0–20 g/ml) has similar dose-dependent estrogenic effects on ERa and ERb in the absence of estradiol (E2). Co-expression of AhR does not affect the estrogenic effects of CSSP. The estrogenicity of CSSP at 20 g/ml is comparable to that exhibited by 1 nM E2 in all the cell lines examined. Cotreatment of cells with CSSP and E2 leads to an additive estrogenic response in ERa+ cells, whereas the cotreatement does not alter or improve E2-induced ERb activation. To check whether the estrogenic activity of CSSP is mediated through ERa and ERb, a pure antiestrogen compound ICI 182780 is used to block the binding of ligands to these ERs. ICI 182780 at 10 nM can efficiently prevent E2 from activating ERa and ERb. This concentration of ICI 182780 does not affect the estrogenic effect of CSSP on ERa regardless of the presence and absence of E2, but it reduces the estrogenic effect on ERb. These results suggest that (1) CSSP can activate ERa and ERb by a mechanism independent of ligand binding, and (2) CSSP contains some components that can act as ERb ligands. doi:10.1016/j.toxlet.2010.03.221
P103-012 Bisphenol A-induced aromatase activation is mediated by camp response element activation in rat testicular Leydig cells E.H. Han 1 , J.Y. Kim 1 , K.Y. Lee 2 , H.G. Jeong 1 1
Chungnam National University, Republic of Korea, 2 Chonnam National University, Republic of Korea Bisphenol A (4,4 -dihydroxy-2,2-diphenylpropane; BPA) is an endocrine disruptor that affects the reproductive health of wildlife and possibly of humans. We evaluated the effect of BPA on aromatase expression in rat testicular Leydig cells. BPA induced a time- and concentration-dependent increase in aromatase protein expression in rat testicular Leydig R2C cells. It also increased aromatase gene expression and its enzyme and promoter activity, but reduced testosterone synthesis; the production of prostaglandin E2 (PGE2), and the gene expression of PGE2 (EP2 and EP4) receptors; induced the activation of cyclic adenosine monophosphate (cAMP) response element (CRE) and CREB binding; and increased the phosphorylation of protein kinase A (PKA), Akt, and mitogenactivated protein (MAP) kinase signaling pathways. Taken together, these results suggest that BPA increases aromatase activity mediated by the CRE, PKA, Akt, and MAP kinase signaling pathways in rat testicular Leydig cells. doi:10.1016/j.toxlet.2010.03.222
P103-011 Estrognic effect of second-hand cigarette smoke in lung cancer cell lines expressing different receptor phenotypes L.C. Kuo, S.F. Lin, L.A. Li National Health Research Institutes/Division of Environmental Health & Occupational Medicine, Taiwan Increasing evidence shows that women are more vulnerable to lung cancer than men, suggesting that estrogen plays a role in the pathology of this cancer. Cigarette smoke contains enormous estrogen-like polycyclic aromatic hydrocarbons that may alter the activity of estrogen receptors (ERs) directly or indirectly through aryl hydrocarbon receptor (AhR). Here we examine estrogenic and antiestrogenic effects of a condensate of cigarette side-stream particulates (CSSP) in lung cancer cell lines that are engineered to exhibit different ER/AhR phenotypes by reporter transfection anal-
P103-013 BDE-99 exposed rats: An assessment of the hormonal status and biochemical parameters in adult animals V. Alonso, M. Bellés, M.L. Albina, V. Linares, A. Pujol, D. Sánchez, J.L. Domingo School of Medicine, IISPV “Universitat Rovira i Virgili”, Spain Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants. Among them, the 2,2 ,4,4 ,5-pentabromodiphenyl ether (BDE-99) is one of the most persistent congeners in wildlife and humans. Although developmental neurotoxicity of PBDEs has been investigated, little is known about their toxicological effects in adulthood. The aim of this study was to assess in adult rats the effects of BDE-99 on the hormonal status and biochemical parameters. Animals (10 per group) were given by gavage a single dose of
Abstracts / Toxicology Letters 196S (2010) S37–S351
0, 0.6, or 1.2 mg BDE-99/kg of body weight. After 45 days, urine and blood samples were collected for biochemical analysis, including the determination of oxidative stress (OS) markers. In urine, lactate dehydrogenase (LDH), ␥-glutamil-transferase (GGT), and N-acetil-d-glucosaminidase (NAG) activities significantly decreased at 1.2 mg BDE-99/kg. The urinary excretion of total protein significantly increased at both BDE-99 doses. In blood, BDE-99 caused an increase in glutamyl pyruvic transaminase (GPT), glutamyl oxaloacetic transaminase (GOT), and alkaline phosphatase (ALP) activities at 1.2 mg/kg. In turn, a significant decrease in uric acid levels was observed in all BDE-99 treated animals. The analysis of blood OS markers revealed a significant increase in superoxide dismutase (SOD) activity, while glutathione reductase (GR) activity significantly decreased in both BDE-99 treated groups. In urine, isoprostane levels increased following BDE-99 exposure. On the other hand, the serum levels of testosterone significantly decreased in rats treated with BDE-99. Progesterone levels significantly decreased at 1.2 mg BDE-99/kg. These results demonstrate that exposure of adult rats to BDE-99 interacts with the hormonal response. Moreover, alterations in biochemical parameters showed signs of renal and hepatic toxicity. Further investigations on the mechanism of action of BDE-99 are clearly necessary in order to establish the potential human health risks of this pollutant. doi:10.1016/j.toxlet.2010.03.223
P103-014 Concentrations of urinary phthalates metabolites in Mexican women with and without diabetes K. Svensson 1 , R.U. Hernández-Ramírez 2 , A. Burguette 2 , M. Cebrian 3 , L. Claudio 4 , L. López-Carrillo 2 1
Graduate School of Public Health, University of Puerto Rico, United States, 2 National Institute of Public Health, Cuernavaca, Morelos, Mexico, 3 Sección Externa de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico, 4 Department of Community and Preventive Medicine, Mount Sinai School of Medicine, NY, United States
Background: Phthalates are ubiquitous industrial chemicals used as plasticizers in plastics made of polyvinyl chloride (PVC) to confer flexibility and durability. Phthalates have been associated with several adverse health effects, and recently it has been proposed that exposure to phthalates, could have an effect on metabolic homeostasis. Therefore, this exploratory cross-sectional study evaluated the possible association between phthalate exposure and self-reported diabetes among adult Mexican women. Methods: As part of an on-going case-control study only controls were selected, which constituted 221 healthy women matched by age (±5 years) and place of residence with the cases. Women with diabetes were identified by self-report and a urine sample of each woman was collected to measure the urinary concentrations of nine phthalate metabolites. The association between phthalates metabolites and diabetes were assessed by logistic regression models. Results: The exposure levels of phthalate metabolites varied by diabetes status. Participants with diabetes had significantly higher levels of the metabolites MEHHP, MEOHP, MECPP and the sum of DEHP metabolites (DEHP), but lower levels of MBzP, compared to participants without diabetes (p-value <0.05). Moreover, two associations remained marginally significant (MEHHP: p for trend = 0.063, and MEOHP: p for trend = 0.079; respectively), even after adjusting for age and education. Conclusions: This exploratory cross-sectional study found significant association between phthalate metabolites and diabetes status. Phthalate exposure could have an effect on
S57
the human metabolism and also play an important role on the prevalence of diabetes. doi:10.1016/j.toxlet.2010.03.224
P103-015 Nanoparticle-rich diesel exhaust-disrupted testosterone biosynthesis and metabolism might be mediated by growth hormone D.H. Ramdhan 1 , Y. Ito 2 , Y. Yanagiba 1 , N. Yamagishi 1 , Y. Hayashi 1 , A.K. Suzuki 3 , T. Nakajima 1 1
Nagoya University Graduate School of Medicine, Japan, 2 Nagoya City University Graduate School of Medicine, Japan, 3 Japan National Institute for Environmental Studies, Research Center for Environmental Risk, Japan
Diesel exhaust particles (DEPs), which are ubiquitously present air pollutants resulting from increased use of vehicles, have hazardous effects on human health, as reported in numerous epidemiological studies showing associations between DEP exposure and cardiovascular disease, allergic rhinitis, pulmonary cancer, and disruption of reproductive function. DEP contains amounts of small particles ranging from nanoparticles (NP) to coarse particles. This suggests that much more attention should be paid to the adverse effects of NPs (NR-DE) included in DEPs. We previously reported that exposure to low (22.5 ± 0.2 nm in diameter, 15.4 ± 1.0 g/m3 in mass weight, 2.27 × 105 /cm3 in mean number concentration), and medium (26.1 ± 0.5 nm, 36.4 ± 1.2 g/m3 , 5.11 × 105 /cm3 ) concentrations of nanoparticle-rich diesel exhaust (NR-DE) for one and two months (5 h/day, 5 days/week) significantly increased plasma testosterone in male Fischer 344 rats, whereas exposure to a high concentration (27.1 ± 0.5 nm, 168.8 ± 2.7g/m3 , 1.36 × 106 /cm3 ) did not. The present study attempts to clarify the mechanism of this elevation. Low and medium exposures to NR-DE for one and two months significantly increased steroidogenic acute regulatory protein (StAR)- and cytochrome P450 side-chain cleavage (P450scc)-mRNA and their protein expressions in the testis of rats, in which the elevation pattern was very similar to that of plasma testosterone levels. Interestingly, both exposure levels for one month significantly increased growth hormone (GH) receptor expression in the testis, and low exposure also increased testicular insulin-like growth factor I-mRNA levels and hepatic microsomal cytochrome P450 2C11-mRNA and their protein levels in rats. These two factors are thought to be related to growth hormone secretion. Disruption of testosterone biosynthesis by NR-DE exposure may be a mode of action for reproductive toxicity, which may, in part, be regulated by increasing StAR and P450scc expressions via GH signalling. doi:10.1016/j.toxlet.2010.03.225
P103-016 Flavone regulation of steroidogenic CYP11B1 and CYP11B2 genes L.C. Cheng, J.R. Lin, L.A. Li Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan Recent years there are growing interests in flavonoids, a group of polyphenolic compounds present abundantly in plants, because of their pharmacological potential in anti-inflammation, antiox-