Like other persistent organochlorine pesticides, endosulfan residues have been detected in foods including fruit, vegetables, and fish. The aim of our study was to assess the impact of a dietary exposure to low doses of endosulfan from foetal development until adult age on metabolic homeostasis in mice and to identify biomarkers of exposure using an 1H-NMR-based metabonomic approach in various tissues and biofluids. We report in both genders an increase in plasma glucose as well as changes in levels of factors involved in the regulation of liver oxidative stress, confirming the prooxidant activities of this compound. Some metabolic changes were distinct in males and females. For example in plasma, a decrease in lipid LDL and choline content was only observed in female. Lactate levels in males were significantly increased. In conclusion, our results show that metabolic changes in liver could be linked to the onset of pathologies like diabetes and insulin resistance. Moreover from our results it appears that the NMR-based metabonomic approach could be useful for the characterization in plasma of a dietary exposure to low dose of pesticide in human. 1. Introduction Many epidemiological studies have shown that exposure to pesticides is a risk factor for human health, as evidenced by the positive correlation between professional exposure to these compounds and an increase in the incidence of various human diseases (reviewed in Merhi et al. [1]). The general population is also exposed to pesticides mainly via food intake. Thus many people have a lifelong exposure to low doses of pesticides, the impact of which on human health is not yet known. Organochlorine (OC) pesticides are among the most frequent contaminants found in the environmental compartments because they persist in the environment and bioaccumulate in organisms, partly due to their lipophilic properties [2]. Endosulfan is a chlorinated cyclodiene pesticide which was first severely restricted then banned in 2006 in several European Union countries. Nevertheless, the general population continues to be exposed: like other persistent organochlorine pesticides, endosulfan residues have been detected in several foods including fruits, vegetables, and fish [3]. There is an evidence that endosulfan is acutely poisonous to humans through both accidental and intentional exposure [4]. Endosulfan is classified by the World Health Organisation as a moderately hazardous (class II) pesticide [5]; however, it is genotoxic [6] and is an endocrine disrupter displaying xenooestrogenic activity [7]. Endosulfan has
References
[1]
M. Merhi, H. Raynal, E. Cahuzac, F. Vinson, J. P. Cravedi, and L. Gamet-Payrastre, “Occupational exposure to pesticides and risk of hematopoietic cancers: meta-analysis of case-control studies,” Cancer Causes and Control, vol. 18, no. 10, pp. 1209–1226, 2007.
[2]
M. Mariscal-Arcas, C. Lopez-Martinez, A. Granada, N. Olea, M. L. Lorenzo-Tovar, and F. Olea-Serrano, “Organochlorine pesticides in umbilical cord blood serum of women from Southern Spain and adherence to the Mediterranean diet,” Food and Chemical Toxicology, vol. 48, no. 5, pp. 1311–1315, 2010.
[3]
EFSA, “2008 Annual report on pesticide residues according to article 32 of Regulation (EC) No. 396/2005,” EFSA Journal, vol. 8, no. 7, p. 1646, 2010.
[4]
M. H. Silva and S. L. Beauvais, “Human health risk assessment of endosulfan. I: toxicology and hazard identification,” Regulatory Toxicology and Pharmacology, vol. 56, no. 1, pp. 4–17, 2010.
[5]
WHO, The WHO Recommended Classification of Pesticides by Hazard and Guidelines to Classification 2000–2002, World Healthg Organisation, International Programme on Chemical Safety/Inter-Organisation Programme for Sound Management of Chemicals, Geneva, Switzerland, 2002.
[6]
M. Bajpayee, A. K. Pandey, S. Zaidi et al., “DNA damage and mutagenicity induced by endosulfan and its metabolites,” Environmental and Molecular Mutagenesis, vol. 47, no. 9, pp. 682–692, 2006.
[7]
J. Varayoud, L. Monje, T. Bernhardt, M. Mu？oz-de-Toro, E. H. Luque, and J. G. Ramos, “Endosulfan modulates estrogen-dependent genes like a non-uterotrophic dose of 17β-estradiol,” Reproductive Toxicology, vol. 26, no. 2, pp. 138–145, 2008.
[8]
P. K. Gupta and S. V. Chandra, “Toxicity of endosulfan after repeated oral administration to rats,” Bulletin of Environmental Contamination and Toxicology, vol. 18, no. 3, pp. 378–384, 1977.
[9]
R. Hack, E. Ebert, and K. H. Leist, “Chronic toxicity and carcinogenicity studies with the insecticide endosulfan in rats and mice,” Food and Chemical Toxicology, vol. 33, no. 11, pp. 941–950, 1995.
[10]
N. Sinha, R. Narayan, and D. K. Saxena, “Effect of endosulfan on the testis of growing rats,” Bulletin of Environmental Contamination and Toxicology, vol. 58, no. 1, pp. 79–86, 1997.
[11]
F. N. Bebe and M. Panemangalore, “Exposure to low doses of endosulfan and chlorpyrifos modifies endogenous antioxidants in tissues of rats,” Journal of Environmental Science and Health B, vol. 38, no. 3, pp. 349–363, 2003.
[12]
R. C. T. Casabar, P. C. Das, G. K. DeKrey et al., “Endosulfan induces CYP2B6 and CYP3A4 by activating the pregnane X receptor,” Toxicology and Applied Pharmacology, vol. 245, no. 3, pp. 335–343, 2010.
[13]
O. Ozmen, S. Sahinduran, and F. Mor, “Pathological and immunohistochemical examinations of the pancreas in subacute endosulfan toxicity in rabbits,” Pancreas, vol. 39, no. 3, pp. 367–370, 2010.
[14]
R. Pathak, S. G. Suke, T. Ahmed et al., “Organochlorine pesticide residue levels and oxidative stress in preterm delivery cases,” Human and Experimental Toxicology, vol. 29, no. 5, pp. 351–358, 2010.
[15]
T. Cabaleiro, A. Caride, A. Romero, and A. Lafuente, “Effects of in utero and lactational exposure to endosulfan in prefrontal cortex of male rats,” Toxicology Letters, vol. 176, no. 1, pp. 58–67, 2008.
[16]
J. K. Nicholson, J. C. Lindon, and E. Holmes, “‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data,” Xenobiotica, vol. 29, no. 11, pp. 1181–1189, 1999.
[17]
K. A. Aliferis and M. Chrysayi-Tokousbalides, “Metabolomics in pesticide research and development: review and future perspectives,” Metabolomics, vol. 7, no. 1, pp. 35–53, 2011.
[18]
S. A. E. Brown, J. R. McKelvie, A. J. Simpson, and M. J. Simpson, “1H NMR metabolomics of earthworm exposure to sub-lethal concentrations of phenanthrene in soil,” Environmental Pollution, vol. 158, no. 6, pp. 2117–2123, 2010.
[19]
H. P. Wang, Y. J. Liang, D. X. Long, J. X. Chen, W. Y. Hou, and Y. J. Wu, “Metabolic profiles of serum from rats after subchronic exposure to chlorpyrifos and carbaryl,” Chemical Research in Toxicology, vol. 22, no. 6, pp. 1026–1033, 2009.
[20]
L. Wei, P. Liao, H. Wu et al., “Metabolic profiling studies on the toxicological effects of realgar in rats by 1H NMR spectroscopy,” Toxicology and Applied Pharmacology, vol. 234, no. 3, pp. 314–325, 2009.
[21]
“Joint FAO/WHO meeting on pesticide residues: pesticide residues in food 2010,” Report of the Joint Meeting of the FAO Panel of Experts OnPesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues, Rome, Italy, September 2010.
[22]
M. Merhi, C. Demur, C. Racaud-Sultan et al., “Gender-linked haematopoietic and metabolic disturbances induced by a pesticide mixture administered at low dose to mice,” Toxicology, vol. 267, no. 1–3, pp. 80–90, 2010.
[23]
J. Folch, I. Ascoli, M. Lees, J. A. Meath, and N. Le Baron, “Preparation of lipide extracts from brain tissue,” The Journal of Biological Chemistry, vol. 191, no. 2, pp. 833–841, 1951.
[24]
N. J. Waters, E. Holmes, C. J. Waterfield, R. D. Farrant, and J. K. Nicholson, “NMR and pattern recognition studies on liver extracts and intact livers from rats treated with α-naphthylisothiocyanate,” Biochemical Pharmacology, vol. 64, no. 1, pp. 67–77, 2002.
[25]
J. A. Westerhuis, H. C. J. Hoefsloot, S. Smit et al., “Assessment of PLSDA cross validation,” Metabolomics, vol. 4, no. 1, pp. 81–89, 2008.
[26]
S. Wold, H. Antti, F. Lindgren, and J. ？hman, “Orthogonal signal correction of near-infrared spectra,” Chemometrics and Intelligent Laboratory Systems, vol. 44, no. 1-2, pp. 175–185, 1998.
[27]
I. Rana and T. Shivanandappa, “Mechanism of potentiation of endosulfan cytotoxicity by thiram in Ehrlich ascites tumor cells,” Toxicology In Vitro, vol. 24, no. 1, pp. 40–44, 2010.
[28]
M. Aggarwal, S. B. Naraharisetti, S. Dandapat, G. H. Degen, and J. K. Malik, “Perturbations in immune responses induced by concurrent subchronic exposure to arsenic and endosulfan,” Toxicology, vol. 251, no. 1–3, pp. 51–60, 2008.
[29]
P. R. Dalsenter, E. Dallegrave, J. R. B. Mello, A. Langeloh, R. T. Oliveira, and A. S. Faqi, “Reproductive effects of endosulfan on male offspring of rats exposed during pregnancy and lactation,” Human and Experimental Toxicology, vol. 18, no. 9, pp. 583–589, 1999.
[30]
T. Ahmed, R. Pathak, M. Mustafa et al., “Ameliorating effect of N-acetylcysteine and curcumin on pesticide-induced oxidative DNA damage in human peripheral blood mononuclear cells,” Environmental Monitoring and Assessment, vol. 179, no. 1–4, pp. 293–299, 2011.
[31]
S. Ozdem, C. Nacitarhan, M. S. Gulay, F. S. Hatipoglu, and S. S. Ozdem, “The effect of ascorbic acid supplementation on endosulfan toxicity in rabbits,” Toxicology and Industrial Health, vol. 27, no. 5, pp. 437–446, 2011.
[32]
R. Saxena, P. Garg, and D. K. Jain, “In vitro anti-oxidant effect of vitamin e on oxidative stress induced due to pesticides in rat erythrocytes,” Toxicology International, vol. 18, no. 1, pp. 73–76, 2011.
[33]
F. Vinson, M. Merhi, I. Baldi, H. Raynal, and L. Gamet-Payrastre, “Exposure to pesticides and risk of childhood cancer: a meta-analysis of recent epidemiological studies,” Occupational and Environmental Medicine, vol. 68, no. 9, pp. 694–702, 2011.
[34]
Y. Kalender, S. Kalender, M. Uzunhisarcikli, A. Ogutcu, F. A？ikgoz, and D. Durak, “Effects of endosulfan on B cells of Langerhans islets in rat pancreas,” Toxicology, vol. 200, no. 2-3, pp. 205–211, 2004.
[35]
D. H. Lee, I. K. Lee, M. Porta, M. Steffes, and D. R. Jacobs Jr., “Relationship between serum concentrations of persistent organic pollutants and the prevalence of metabolic syndrome among non-diabetic adults: results from the national health and nutrition examination survey 1999–2002,” Diabetologia, vol. 50, no. 9, pp. 1841–1851, 2007.
[36]
H. J. Schirra, C. G. Anderson, W. J. Wilson et al., “Altered metabolism of growth hormone receptor mutant mice: a combined NMR metabonomics and microarray study,” PLoS ONE, vol. 3, no. 7, Article ID e2764, 2008.
[37]
T. O. Street, D. W. Bolen, and G. D. Rose, “A molecular mechanism for osmolyte-induced protein stability,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 38, pp. 13997–14002, 2006.
[38]
N. S. El-Shenawy, “Effects of insecticides fenitrothion, endosulfan and abamectin on antioxidant parameters of isolated rat hepatocytes,” Toxicology In Vitro, vol. 24, no. 4, pp. 1148–1157, 2010.
[39]
S. Narayan, H. M. Dani, and U. K. Misra, “Changes in lipid profiles of liver microsomes of rats following intratracheal administration of DDT or endosulfan,” Journal of Environmental Science and Health B, vol. 25, no. 2, pp. 243–257, 1990.
[40]
D. Desoubzdanne, C. Claparols, N. Martins-Froment et al., “Analysis of hydrophilic and lipophilic choline compounds in radioresistant and radiosensitive glioblastoma cell lines by HILIC-ESI-MS/MS,” Analytical and Bioanalytical Chemistry, vol. 398, no. 6, pp. 2723–2730, 2010.
[41]
H. Shimizu, T. Kumabe, R. Shirane, and T. Yoshimoto, “Correlation between choline level measured by proton MR spectroscopy and Ki-67 labeling index in gliomas,” American Journal of Neuroradiology, vol. 21, no. 4, pp. 659–665, 2000.
[42]
Q. Zhang, J. Z. Hu, D. N. Rommereim et al., “Application of high-resolution 1H MAS NMR spectroscopy to the analysis of intact bones from mice exposed to gamma radiation,” Radiation research, vol. 172, no. 5, pp. 607–616, 2009.
[43]
M. H. Silva and D. Gammon, “An assessment of the developmental, reproductive,and neurotoxicity of endosulfan,” Birth Defects Research B, vol. 86, no. 1, pp. 1–28, 2009.
[44]
J. A. Gonzalez-Correa, J. P. De La Cruz, E. Martin-Aurioles, M. A. Lopez-Egea, P. Ortiz, and F. Sanchez De La Cuesta, “Effects of S-adenosyl-L-methionine on hepatic and renal oxidative stress in an experimental model of acute biliary obstruction in rats,” Hepatology, vol. 26, no. 1, pp. 121–127, 1997.
[45]
F. Hincal, A. Gurbay, and B. Giray, “Induction of lipid peroxidation and alteration of glutathione redox status by endosulfan,” Biological Trace Element Research, vol. 47, no. 1–3, pp. 321–326, 1995.
[46]
B. D. Banerjee and Q. Z. Hussain, “Effect of sub-chronic endosulfan exposure on humoral and cell-mediated immune responses in albino rats,” Archives of Toxicology, vol. 59, no. 4, pp. 279–284, 1986.
