Abstract
Background and aims
Because of the widespread use of pesticides for domestic and industrial applications, the evaluation of their toxic effects is of major concern to public health. The aim of the present study was to investigate the propensity of dimethoate (DM), an organophosphorus pesticide, to cause oxidative damage in the liver and kidney of mice and its associated genotoxic effect.
Methods
DM was administered intraperitoneally at doses of 1, 5, 10, 15, and 30 mg/kg body weight for 30 consecutive days in BALB/c mice. Oxidative stress was monitored in the kidney and liver by measuring malondialdehyde level, protein carbonyl concentration, and the catalase activity. The genotoxicity of DM was assessed by the comet assay in vivo.
Results and discussion
Our results indicated that DM inhibited acetylcholinesterase activities in the liver and kidney of treated mice. DM increased lipid peroxidation and protein carbonyl levels in the liver and kidney in a dose-dependent manner. Catalase activity was found to be significantly increased in the liver and kidney at doses higher than 5 mg/kg body weight.
Conclusions
Our study demonstrated that DM induced DNA damage in the liver and kidney of treated mice in a dose-dependent manner; this induction was associated to DM-induced oxidative stress. Further investigations are needed to prove the implication of oxidative stress in genotoxicity induced by DM.
Similar content being viewed by others
References
Abdollahi M, Ranjbar A, Shadnia S, Nikfar S, Rezaiee A (2004a) Pesticides and oxidative stress: a review. Med Sci Monit 106:141–147
Abdollahi M, Donyavi M, Pournourmohammadi S, Saadat M (2004b) Hyperglycemia associated with increased hepatic glycogen phosphorylase and phosphenol pyruvate carboxykinase in rats following sub-chronic exposure to malathion. Comp Biochem Physiol C Toxicol Appl Pharmacol 137:343–347
Akhgari M, Abdollahi M, Kebryaeezadeh A, Hosseini R, Sabzevari O (2003) Biochemical evidence for free radical-induced lipid peroxidation as a mechanism for sub chronic toxicity of malathion in blood and liver of rats. Hum Exp Toxicol 22:205–211
Alavanja MC (2009) Introduction: pesticides use and exposure extensive worldwide. Rev Environ Health 24(4):303–309
Aprea C, Sciarra G, Sartorelli P (1998) Environmental and biological monitoring of exposure to mancozeb, ethylenethiourea, and dimethoate during industrial formulation. J Toxicol Environ Health 53:263–281
Aprea C, Terenzoni B, De Angelis V, Sciarra G, Lunghini L, Borzacchi G, Vasconi D, Fani D, Quercia A, Salvan A, Settimi L (2004) Evaluation of skin and respiratory doses and urinary excretion of alkylphosphates inworkers exposed to dimethoate during treatment of olive trees. Arch Environ Contam Toxicol 48:127–134
Astiz M, de Alaniz MJ, Marra CA (2009a) Effect of pesticides on cell survival in liver and brain rat tissues. Ecotoxicol Environ Saf 72(7):2025–2032
Astiz M, Hurtado de Catalfo GE, de Alaniz MJ, Marra CA (2009b) Involvement of lipids in dimethoate-induced inhibition of testosterone biosynthesis in rat interstitial cells. Lipids 44(8):703–718
Aust SD (1989) Metal ions, oxygen radicals and tissue damage. Bibl Nutr Dieta 43:266–277
Banerjee BD, Seth V, Bhattacharya A, Pasha ST, Chakraborty AK (1999) Biochemical effects of pesticides on lipid peroxidation and free radical scavengers. Toxicol Lett 107:33–47
Basu AK, Marnett LJ (1983) Unequivocal demonstration that malondialdehyde is a mutagen. Carcinogenesis 4:331–333
Bianchi L, Zannoli A, Pizzala R, Stivala RA, Chiesara E (1994) Genotoxicity assay of five pesticides and their mixtures in Saccharomyces cerevisia D7. Mutat Res 321:203–211
Bjelland S, Seeberg E (2003) Mutagenicity, toxicity and repair of DNA base damage induced by oxidation. Mutat Res 531(1–2):37–80
Bolognesi C (2003) Genotoxicity of pesticides: a review of human biomonitoring studies. Mutat Res 543:251–272
Bradford MM (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Cadet J, Douki T, Gasparutto D, Ravanat JL (2003a) Oxidative damage to DNA: formation, measurement and biochemical features. Mutat Res 531:5–23
Cadet J, Douki T, Ravanat JL (2003b) The human genome as a target of oxidative modifications: damage to nucleic acids. In: Fuchs J, Podda M, Packer F (eds) Redox genome interactions and disease, chapter 8. Marcel Dekker, New York, pp 143–189
Clairbone A (1985) Catalase activity. Handbook of methods for oxygen radical research. CRC, Boca Raton, pp 283–284
Collins A, Harrington V (2002) Repair of oxidative DNA damage: assessing its contribution to cancer prevention. Mutagenesis 17(6):489–493
Collins AR, Dusinska M, Gedik CM, Stetina R (1996) Oxidative damage to DNA: do we have a reliable biomarker? Environ Health Perspect 104(Supp 4):465–469
Debnath D, Mandal TK (2000) Study of quinalphos (an environmental oestrogenic insecticide) formulation (Ekalux 25 E.C.)-induced damage of the testicular tissues and antioxidant defense systems in Sprague–Dawley albino rats. J Appl Toxicol 20:197–204
Dedek W, Grahl R, Schmidt R (1984) A comparative study of guanine N7-alkylation in mice in vivo by the organophosphorus insecticides trichlorphon, dimethoate, phosmet and bromophos. Acta Pharmacol Toxicol 55:104–109
Eckl PM, Ortner A, Esterbauer H (1993) Genotoxic properties of 4-hydroxyalkenals and analogous aldehydes. Mutat Res 290(2):183–192
Ellingham TJ, Christensen EA, Maddock MB (1986) In vitro induction of sister chromatid exchanges and chromosomal aberrations in peripheral lymphocytes of the oyster toadfish and American eel. Environ Mutagen 8:555–569
Ellman GL, Courney KD, Andres V, Featherstone RM (1961) Anewand rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharm 7:88–95
Emerit I (1994) Reactive oxygen species, chromosome mutation, and cancer: possible role of clastogenic factors in carcinogenesis. Free Radic Biol Med 16:99–109
EPA (1999) Memorandum, updated, revised dimethoate. The updated, revised HED chapter of the re-registration, eligibility decision document (RED). PC code: 035001, case no. 0088. Epa J, Washington, DC
Esterbauer H (1993) Cytotoxicity and genotoxicity of lipid-oxidation products. Am J Clin Nutr 57:779–786
Fahrig R (1974) Comparative mutagenicity studies with pesticides. IARC Sci Publ 10:161–181
Farag AT, El-Aswad AF, Shaaban NA (2007) Assessment of reproductive toxicity of orally administered technical dimethoate in male mice. Reprod Toxicol 23(2):232–238
Gillot-Delhalle J, Coluzzi A, Moutschen J, Moutschen-Dahmen M (1983) Mutagenicity of some organophosphorus compounds at the ade-6 locus of Scizosaccharomyces pombe. Mutat Res 117:139–148
Gomes J, Dawodu AH, Lloyd O, Revitt DM, Anilal SV (1999) Hepatic injury and disturbed amino acid metabolism in mice following prolonged exposure to organophosphorus pesticides. Hum Exp Toxicol 18:33–37
Hagar HH, Fahmy AH (2002) A biochemical, histochemical, and ultrastructural evaluation of the effect of dimethoate intoxication on rat pancreas. Toxicol Lett 133:161–170
Haworth S, Lawlor T, Mortelmans K, Speck W, Zeiger E (1983) Salmonella mutagenesis test results for 250 chemicals. Environ Mutagen 5:3–142
Hughes CM, Lewis SE, McKelvey-Martin VJ, Thompson W (1996) A comparison of baseline and induced DNA damage in human spermatozoa from fertile and infertile men, using a modified comet assay. Mol Hum Reprod 2:613–619
IARC (1983) Miscellaneous pesticides. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol 30. IARC, Lyon
IARC (1991) Occupational exposures in insecticide application and some pesticides. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol 53. IARC, Lyon
Institóris L, Siroki O, Dési I (1995) Immunotoxicity study of repeated small doses of dimethoate and methylparathion administered to rats over three generations. Hum Exp Toxicol 14(11):879–883
Institóris L, Siroki O, Dési I, Undeger U (1999) Immunotoxicological examination of repeated dose combined exposure by dimethoate and two heavy metals in rats. Hum Exp Toxicol 18(2):88–94
IPCS/WHO (2001) Classification of pesticides by hazard and guidelines to classification. Geneva, Switzerland
Kamath V, Rajini PS (2007) Altered glucose homeostasis and oxidative impairment in pancreas of rats subjected to dimethoate intoxication. Toxicology 231:137–146
Kamath V, Joshi AKR, Rajini PS (2008) Dimethoate induced biochemical perturbations in rat pancreas and its attenuation by cashew nut skin extract. Pestic Biochem Phys 90:58–62
Kasai H, Kumeno K, Yamaizumi Z, Nishimura S, Nagao M, Fujita Y (1982) Mutagenicity of methylglyoxal in coffee. Gann 73:681–683
Konradsen F (2007) Acute pesticide poisoning—a global public health problem. Dan Med Bull 54(1):58–59
Ladhar SS, Grover IS, Radhawa SK (1990) Mutagenicity of systemic organophosphate pesticides metasystox and rogor. Ind J Exp Biol 28:390–391
Lopes S, Jurisicova A, Sun JG, Casper RF (1998) Reactive oxygen species: potential cause for DNA fragmentation in human spermatozoa. Hum Reprod 13:896–900
Mahadevaswami MP, Kaliwal BB (2002) Effect of dimethoate administration schedules on compensatory ovarian hypertrophy, follicular dynamics, and estrous cycle in hemicastrated mice. J Basic Clin Physiol Pharmacol 13(3):225–248
Mahadevaswami MP, Kaliwal BB (2004) Evaluation of dimethoate toxicity on pregnancy in albino mice. J Basic Clin Physiol Pharmacol 15(3–4):211–221
Mahjoubi-Samet A, Fetoui H, Zeghal N (2008) Nephrotoxicity induced by dimethoate in adult rats and their suckling pups. Pestic Biochem Physiol 91:96–103
Marnett LJ (2000) Oxyradicals and DNA damage. Carcinogenesis 21:361–370
Marnett LJ, Hurd HK, Hollstein MC, Levin DE, Esterbauer H, Ames BN (1985) Naturally occurring carbonyl compounds are mutagens in Salmonella tester strain TA104. Mutat Res 148:25–34
Mehl A, Rolseth V, Gordon S, Bjoraas M, Seeberg E, Fonnum F (2000) Brain hypoplasia caused by exposure to trichlorfon and dichlorvos during development can be ascribed to DNA alkylation damage and inhibition of DNA alkyltransferase repair. Neurotoxicology 21:165–173
Mercier Y, Gatellier P, Renerre M (2004) Lipid and protein oxidation in vitro, and antioxidant potential in meat from Charolais cows finished on pasture or mixed diet. Meat Sci 66:467–473
Mittler R (2002) Oxidative stress, antioxidants and stress tolerance. Trends Plant Sci 7(9):405–410
Mohn G (1973) 5-Methyl tryptophan resisttance mutations in Escherichia coli K-12. Mutagenic activity of monofunctional alkylating agents including organophosphorus insecticides. Mutat Res 20:7–15
Moriya M, Ohta T, Watanabe K, Miyazawa T, Kato K, Shirasu Y (1983) Further mutagenicity studies on pesticides in bacterial reversion assay system. Mutat Res 113:173–180
Mukai FH, Goldstein BD (1976) Mutagenicity of malonaldehyde, a decomposition product of peroxidized polyunsaturated fatty acids. Science 191:868–869
Nackerdien Z, Rao G, Cacciuttolo MA, Gajewski E, Dizdaroglu M (1991) Chemical nature of DNA–protein cross-links produced in mammalian chromatin by hydrogen peroxide in the presence of iron or copper ions. Biochemistry 30:4873–4879
Nehéz M, Dési I (1996) The effect of dimethoate on bone marrow cell chromosomes of rats in subchronic four-generation experiments. Ecotoxicol Environ Saf 33(2):103–109
Picada JN, Flores DG, Zettler CG, Marroni NP, Roesler R, Henriques JA (2003) DNA damage in brain cells of mice treated with an oxidized form of apomorphine. Mol Brain Res 114(1):80–85
Piña-Guzmán B, Solis-Heredia MJ, Quintanilla-Vega B (2005) Diazinon alters sperm chromatin structure in mice by phosphorylating nuclear protamines. Toxicol Appl Pharmacol 202:189–198
Ranjbar A, Pasalar P, Abdollahi M (2002) Induction of oxidative stress and acetylcholinesterase inhibition in organophosphorous pesticide manufacturing workers. Hum Exp Toxicol 21:179–182
Reuber MD (1984) Carcinogenicity of dimethoate. Environ Res 34:193
Saafi EB, Louedia M, Elfeki A, Zakhama A, Najjar MF, Hammami M, Achour L (2010) Protective effect of date palm fruit extract (Phoenix dactylifera L.) on dimethoate induced-oxidative stress in rat liver. Exp Toxicol Pathol 63:433–441
Sanderson DM, Edson EF (1964) Toxicological properties of the organophosphorus insecticide dimethoate. Brit J Industry Med 21:52
Sarkar SN, Hazarika A, Hajare S, Kataria M, Malik JK (2003) Influence of malathion pre-treatment on the toxicity of anilofos in male rats: a biochemical interaction study. Toxicology 185:1–8
Sayim F (2007) Dimethoate-induced biochemical and histopathological changes in the liver of rats. Exp Toxicol Pathol 59(3–4):237–243
Sharma Y, Bashir S, Irshad M, Gupta SD, Dogra TD (2005a) Effects of acute dimethoate administration on antioxidant status of liver and brain of experimental rats. Toxicology 206:49–57
Sharma Y, Bashir S, Irshad M, Nagc TC, Dogra TD (2005b) Dimethoate-induced effects on antioxidant status of liver and brain of rats following subchronic exposure. Toxicology 215:173–181
Sivapiriya V, Jayanthisakthisekaran J, Venkatraman S (2006) Effects of dimethoate (O,O,-dimethyl S-methyl carbamoyl methyl phosphorodithioate) and ethanol in antioxidant status of liver and kidney of experimental mice. Pest Biochem Physiol 85:115–121
Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35(3):206–221
Twigg JP, Irvine DS, Aitken RJ (1998) Oxidative damage to DNA in human spermatozoa does not preclude pronucleus formation at intracytoplasmic sperm injection. Hum Reprod 13:1864–1871
Undeger U, Institoris L, Siroki O, Nehez M, Desi I (2000) Simultaneous geno- and immunotoxicological investigations for early detection of organophosphate toxicity in rats. Ecotoxicol Environ Saf 45:43–48
Yonei S, Furui H (1981) Lethal and mutagenic effects of malondialdehyde, a decomposition product of peroxidized lipids, on Escherichia coli with different DNA-repair capacities. Mutat Res 88:23–32
Acknowledgment
This research was supported by the “Ministère Tunisien de l’Enseignement Supérieur et de la Recherche Scientifique et de la Technologie (Laboratoire de Recherche sur les Substances Biologiquement Compatibles: LRSBC)”.
Author information
Authors and Affiliations
Corresponding author
Additional information
Responsible editor: Markus Hecker
Rights and permissions
About this article
Cite this article
Ayed-Boussema, I., Rjiba, K., Moussa, A. et al. Genotoxicity associated with oxidative damage in the liver and kidney of mice exposed to dimethoate subchronic intoxication. Environ Sci Pollut Res 19, 458–466 (2012). https://doi.org/10.1007/s11356-011-0588-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-011-0588-z