Effects of combined exposure to dichlorvos and monocrotophos on blood and brain biochemical variables in rats

Abstract

Dichlorvos (DDVP) and monocrotophos (MC) are systemic insecticides and known to produce cholinergic and non-cholinergic effects. Individual toxic effects of these chemicals are known but their combined effects have not been studied. We studied the effect of concomitant exposure to DDVP and MC on selected biochemical variables suggestive of liver damage, changes in whole brain biogenic amines levels, acetylcholinesterase (AchE) and monoamine oxidase (MAO) activities in rats. Female rats were exposed to DDVP (2.5 mg/kg subcutaneously) and MC (1.8 mg/kg oral) either individually or in combination for 4 weeks. We observed significant decrease in more pronounced depletion in norepinephrine (NE) and dopamine (DA) levels during co-exposure to DDVP and MC. Brain AChE activity increased and activity of MAO showed significant depletion on co-exposure to DDVP and MC. Brain glutathione (GSH) and oxidized glutathione (GSSG) ratio decreased significantly during exposure to DDVP or MC while co-exposure to these toxicants led to a more pronounced depletion of GSH: GSSG ratio. Serum aspartate amino transferase (AST) and alkaline phosphatase (ALP) activities increased significantly on exposure to MC suggesting liver injury, while DDVP alone had no effect on these variables. There were no effects of DDVP and MC exposure on haematological biochemical variables except for depletion in serum glucose level after MC exposure which was more pronounced DDVP + MC during co-exposure. It can be concluded that only moderate synergistic effects occur between MC and DDVP during co-exposure. A more detailed study with variable doses, prolonged exposure and alterations in different brain regions is recommended.

Keywords

combined exposure dichlorvos female rat monocrotophos neurological disorders organ toxicity oxidative stress

References

Infante-Rivard C. , Labuda D. , Krajinovi M. , Sinnett D. Risk of childhood leukemia with exposure to pesticides and with gene polymorphisms. Epidemiology 1999; 10: 481-489.

IARC (Int. Agency Res. Cancer). IARC Monographs on the Evaluation of Carcinogenic Risk to Humans. An updating of IARC Monograph Volume 1 to 42. Suppl. 7. Lyon, France: IARC, 1986.

IARC Occupational Exposures in Insecticide Application, and Some Pesticides. 53: 535. Lyon, France: IARC, 1991.

Fenner-Crisp PE Risk assessment and risk management: the regulatory process, In: Krieger R (ed.) Handbook of Pesticide Toxicology, 2nd ed. 2001.

Fenske RA Pesticide exposure assessment of workers and their families. Occup Med 1997; 12: 221-237.

Ekstrom G. , Akerblom M. Pesticide management in food and water safety: international contributions and national approaches. Rev Environ Contam Toxicol 1990: 114: 23-55.

MacGregor JA , Plunkett LM , Youngren SH , Manley A. , Plunkett JB , Starr TB Humans appear no more sensitive than laboratory animals to the inhibition of red blood cell cholinesterase by dichlorvos. Reg Toxicol Pharmacol 2005; 43: 150-167.

Hsieh BH , Deng JF , Ger J. , Tsai WJ Acetylcholinesterase inhibition and the extrapyramidal syndrome: a review of the neurotoxicity of organophosphate. Neurotoxicol 2001; 122: 423-427.

Agrahari S. , Pandey KC , Gopal K. Biochemical alteration induced by monocrotophos in the blood plasma of fish, Channa punctatus (Bloach). Pest Biochem Physiol 2007; 88: 268-272.

10.

Manley A. , Brown WR , Mennear J. Dichlorvos and mononuclear cell leukemia in Fischer 344 rats: lack of effect of chronic administration on progression of the disease. Int J Toxicol 1997; 16: 21-65.

11.

Gupta RC Classification and uses of organophosphates and carbamates. In: Gupta RC (ed.) Toxicology of organophosphate and cabamate compounds. Burlington, MA: Elsevier/Academic Press, 2006.

12.

Ellman GL Tissue sulfhydryl groups. Arch Biochem 1959 ; 82: 70-77.

13.

Jollow DJ , Mitchell JR , Zamppaglione Z. , Gillette JR Bromobenzene induced liver necrosis. Protective role of glutathione and evidence for 3, 4 -bromobenzene oxide as the hepatotoxic metabolites. Pharmacol. 1974; 11: 151.

14.

Hissin PJ , Hilf R. A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 1974: 74: 214-226.

15.

Fiske CH , Subbarow Y. The colorimetric determination of phosphates. J Biol Chem 1925; 66: 375-379.

16.

Reitman S. , Frankel S. A colorimetric method for the determination of Serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957; 28: 56-63.

17.

Jacobwitz DW , Richardson JS Method for rapid determination of nor epinephrine, dopamine and serotonin in the same brain region. Pharmacol. Biochem. Behav. 1978; 8: 515-519.

18.

Worek F. , Mast U. , Kiderlen D. , Eyes P. Improved determination of acetylcholinesterase activity in human whole blood . Clin Chem Acta 1999; 288: 73-90.

19.

Wurtman RJ , Axelrod J. A sensitive and specific assay for the estimation of monoamine oxidase . Biochem Pharmacol 1969; 12: 1439-1445.

20.

Marrs TC Organophosphate poisoning. Pharmac. Ther. 1993; 58: 51-66.

21.

Peter JV , Cherian AM Organic insecticides. Anaesth Intensive Care. 2000; 28: 11-19.

22.

Verma SK , Kumar V. , Gill KD An acetylcholinesterase-independent mechanism for neurobehavioral impairments after chronic low level exposure to dichlorvos in rats. Pharmacol Biochem Behav 2009; 92: 173-181.

23.

Gupta RC Toxicology of organophosphate and cabamate compounds. Burlington, MA: Elsevier/Academic Press, 2006.

24.

Casida JE , Quistad GB Organophosphate toxicology: safety aspects of non-acetylcholinesterase secondary targets. Chem Res Toxicol 2004; 17: 983-998.

25.

Raheja G. , Gill KD Altered cholinergic metabolism and muscarinic receptor linked second messenger pathways after chronic exposure to dichlorvos in rat brain. Toxicol Ind Health 2007; 23: 25-37.

26.

Praveen M. , Kumar S. Effect of DDVP on the histology and AchE kinetics of heart muscle of Rattus norvegicus. J Environ Biol 2001: 22: 257-261.

27.

Kobayashi H. , Suzuki T. , Sakamoto M. , et al. Brain regional acetyl cholinesterase activity and muscarinic acetylcholine receptors in rats after repeated administration of cholinesterase inhibitors and its withdrawal . Toxicol Appl Pharmacol 2007; 219: 151-161.

28.

Qadri YH , Swamy AN , Rao JV Species differences in brain acetyl cholinesterase response to monocrotophos in vitro. Ecotoxicol Environ Saf 1994; 28: 91-98.

29.

Choudhary S. , Raheja G. , Gupta V. , Gill KD Possible involvement of dopaminergic neurotransmitter system in dichlorvos induced. Biochem Mol Biol Biophys 2002; 6: 29-36.

30.

Raheja G. , Gill KD Calcium homeostasis and dichlorvos induced neurotoxicity in rat. Mol Cell Biochem 2004; 232: 13-18.

31.

Siddiqui MKJ , Rahman MF , Mustafa M. , Rahman MF , Bhalerao UT A comparative study of blood changes and brain acetylcholinesterase inhibition by monocrotophos and its analogues in rats . Ecotoxicol. Environ. Safety 1991; 21: 283-89.

32.

Oral B. , Guney M. , Demirin H. , et al. Endometrial damage and apoptosis in rats induced by dichlorvos and ameliorating effect of antioxidant vitamin E and C. Reproductive Toxicol. 2006; 22: 783-790.

33.

Bannerjee BD , Seth V. , Ahmed RS Pesticide induced oxidative stress: Perspectives and trends. Rev Environ Health 2001; 16: 1-40.

34.

Kaur P. , Radotra B. , Minz RW , Gill KD Impaired mitochondrial energy metabolism and neuronal apoptotic cell death after chronic dichlorvos (OP) exposure in rat brain. NeuroToxicol 2007; 28: 1208-1219.

35.

Gultekin F. , Delibas N. , Yasar S. , Kilinc I. In vivo changes in antioxidant systems and protective role of melatonin and a combination of vitamin C and vitamin E on oxidative damage in erythrocytes induced by chlorpyrifosethyl in rats. Arch Toxicol 2001; 75: 88-96.

36.

Ercal N. , Treratphan P. , Hammond TC , Mathews RH , Grannemann NH , Spitz DR In vivo indices of oxidative stress in lead exposed C57BL/6 mice are reduced by treatment with meso-2, 3-dimercaptosuccinic acid or N-acetyl cysteine . Free Rad Biol Med 1996; 21: 157-61.

37.

Menshikov V. The role of erythrocytic acetylcholinesterase in hormonal regulation of adaptation to physical exercise. Human Physiol 2004; 29: 178-82.

38.

Iverson J. Effect of acetylcholine on the secretion of glucagon and insulin from the isolated, perfused canine pancreas. Diabetes 1973; 22: 381-87.

39.

Samols E. , Weir GC , Ramseur R. , Day JA , Patel YC Modulation of pancreatic somatostatin by adrenergic and cholinergic agonists and by hyper- and hypoglycemic sulfonamides. Metabolism 1978; 27: 1219-1221.