Histological and Biochemical Changes in the Liver of Albino Mice on Exposure to Insecticide, Carbosulfan

Carbosulfan (2,3-dihydro-2,2dimethyl-7-benzofuronyl [(dibutyl amino) thio] methyl] a carbamate insecticide and acaricide was administered orally at an effective dose of 48 mg/kg/day to albino mice for 5, 10, 20 and 30 days .Control mice received similar quantities of olive oil. Daily body weights were recorded and mice were sacrificed after 24 hours after the terminal exposure. The histologic examination of liver of the mice treated with carbosulfan for 10, 20 and 30 days revealed the dilation of central vein and sinusoids between hypertrophied hepatocytes. Vacuolization and hyalinization of hepatocytes with loss of radial arrangement. Treatment with carbosulfan for 20 days in female and male mice resulted in a significant decrease in protein and liver glycogen contents in female mice, whereas in male mice the glycogen was not changed significantly in the liver. The cholesterol content was increased significantly in male mice, but in female mice there was no significant change. Treatment with carbosulfan for 30 days caused significant decrease in DNA, RNA, protein, glycogen and significant increase in the level of cholesterol in male and female mice. Temporal study on liver enzymes displays treatment with carbosulfan for 20 days caused significant increase in LDH activity and significant decrease in Na+K+ATPase, Mg++ATPase, Ca++ATPase and no significant change in SDH, ASAT, ALAT, ACP activity in female mice, however in male mice the activity of liver enzymes was not changed significantly. Carbosulfan treatment for 30 days caused significant decrease in SDH, Na+-K+ATPase, Mg++ATPase, Ca++ATPase, ACP activity, whereas LDH, ASAT, ALAT, AKP activity were increased significantly in the liver of male and female mice. The results of the present study suggests that the carbosulfan has adverse effects on liver functions leading to histologic and physiological impairment.
 
REFERENCES
 Abell .L. L, Levy .B. B, Brodie .B. P. and Kendal. F. E (1952) Simplified method for estimation of total cholesterol in serum and demonstration of its specificity. J. Biol. Chem; 195, 357- 361.
 Adhikari, N. and Grover, I. S (1988) Genotoxic effects of some systemic pesticides : in vivo chromosomal aberrations in bone marrow cells in rats. Environ. Mol. Mutagen., 12, 235-242.
Babu, G. R. V., Reddy, G. R., Reddy, A. T. V., Rajendra, W. and Chetty, C. S. (1990) Effect of in vitro of propoxur on calcium dependent ATP hydrolysis and calcium uptake by the rat brain synaptosomes. Biochem. Intrnl., 21, 1089-1094.
 Baligar, P. N. and Kaliwal, B. B(2001) Induction of gonadal toxicity to female rats after chronic exposure to mancozeb. Ind. Health, 39, 235- 243.
Barale, R. C., Seapoli, C., Meli, D., Casini, M., Minunni, A., Marrazzini, N., Loprieno and Barrai, I(1993) Cytogenetic effects of benzimidazoles in mouse bone marrow. Mutation Res., 300, 15- 28.
Bhaynagar, V. K., Saigal, S., Khemani, L. D., Malviya, A. N. (1982) Survey among workers in Pesticide factories. Toxicol. Lett. 10, 129- 132.
Brown, H.R. and Sharma, R.P(1976) Synaptosomal adenosine triphosphatase (ATPase) inhibition by organophosphates. Experentia, 32(12), 1540-1542.
Butler, A.M., Murray, M(1993) Inhibition and inactivation of constitutive cytochromes P450 in rat liver by parathion. Mol. Pharmacol., 43, 902-908.
Carrol, N.V., Langely, R.W. and Row, R.H(1956) Glycogen determination in liver and mode by use of anthrone reagent. J. Biol. Chem., 20, 583-593.
Choudhary, N., Sharma, M, Verma, P., Joshi, S.C(2003) Hepato and nephrotoxicity in rat exposed to endosulfan. J. Environ. Biol., 24, 305-308.
Cid, M.G., Loria, D. and Matos, E(1990) Genotoxicity of the pesticide propoxur and its nitroso derivative, No-propoxur on human lymphocytes in vitro. Mutation Res., 232, 45- 48.
Desaiah, D. (1982) Mechanisms of chlordecone 74 Effects of Carbosulfan on Albino Mice neurotoxicity A Review. Neurotoxicity, 3, 103- 110.
Dikshith, T. S. S., Raizada, R. B., Datta, K. K(1980) Interaction of phosphomidon and Benzene in female rabbits. Ind. J. Exptl. Biol., 18, 1273-1277.
Dikshit, T. S. S., Raizada, R. B., Singh, V., Pandey, M. and Shrivastava, M. K. (1991) Repeated dermal toxicity of Lech. HCH and methyl parathion (So Ec) to female rats (Rattus norvegicus). Ind. J. Exptt Biol., 29, 149-155.
Durham, W. F., Wolfe, H. R. (1962) Measurement of the exposure of workers to pesticides, Bull. Wld. Hlth. Org., 26, 75- 91. Enan E. E. (1983)Comparative biochemical effects of three aliphatic organophosphorus insecticides on white rats. Intrnl. Pest control, 25, 42- 44.
Fukuto, R. T. (1983) Structure-activity relationship in derivatives of anticholinesterase insecticides. In: Pesticide chemistry human welfare and the environment. Pergmen Press Ltd., Headington Hill Hall, Oxford OX3 OBW, England, pp. 203- 212.
Georgieva, V. R., Vactikova, M., Tzoneva and Kappas, A. (1990) Genotoxic activity of Benomyl in different test systems. Environ. Mol. Mutagen., 16, 32-36.
Harper, A.J., Rodwell, V.M., Meyer, P.A(1977) Review of physiological chemistry, 16th ed.Large Medical Pub. Los. Actor., California.
Hayes, W. J., Jr(1982) Pesticides studied in man. Williams and Wilkins Col., Baltimore.
Ivanova- Chemishanska, L (1982) Dithiocarbamates. In : Toxicity of pesticides, health aspects of chemical safety WHO Copenhagen, Interim Document, 9, 158-169.
Jinna, R. R., Ozodinma, J. E. and Desaiah, D(1989) Age related changes in rat brain ATPases during treatment with chlordecone. J. Toxicol. Environ. Hlth., 27, 199- 208.
JMPR (2003) Joint FAO/WHO Meeting on pesticide residues, http://www.who.int/ pes/jmpr/2003.htm.
Kackar, R., Srivastava, M.K., Raizada, R.B(1997) Induction of gonadal toxicity to male rats after chronic exposure to mancozeb. Ind. Health, 35, 104-111.
 King, J. (1965) In: Practical Clinical Enzymology, Edn. Z. Van, D. Norstrand, Co. London, p. 83.
Kinter, W. B., Merkens, L. S., Janiki, R.H., Guarino, A. M. (1972) Studies on the mechanism of toxicity of DDT and PCBS; Disruption of osmoregulation in marine fish. Environ. Hlth. Persps., 8, 169 - 173.
Klassen, C. P. and Plaa, G. L. (1966) Relative effects of various chlorinated hydrocarbons on liver and kidney function in mice. Toxicol. & Appl. Pharmacol., 9, 139.
 Koch, R. B. (1969a) Inhibition of animal tissue ATPase activities by chlorinated hydrocarbon. Pesticides chem. Biol. Interact., 1, 199- 209.
Koch, R. B. (1969a) Chlorinated hydrocarbon insecticide inhibition of rabbit brain ATPase. J. Nero. Chem., 16, 169.
Kostka, G., Palut, D., Kopec-Szlezak, J., Kudwicki, J. K. (2000) Early hepatic changes in rats induced by permethrin in comparison with DDT. Toxicology, 142, 135-143.
Kumar, R., Bindu Madhavi, N.B., Sharma, C. B. (1993) Biodegronulation of a carbamate pesticide, propoxur, in rat tissues. Biomed. Chromatgr., 7, 20-24.
Lowry, H., Rosebrough, N.I., Far, A.L. and Ranall, R.J(1951) Protein measurement with Folinphenol reagent. J. Biol. Chem., 193, 265- 275.
Mahadevaswami, M. P., Jadaramkunti, U. C., Hiremath, M. B and Kaliwal, B. B. (2000) Effect of mancozeb on ovarian compensatory hypertrophy and biochemical constituents in hemicastrated albino rat. Reprod. Toxicol., 14, 127- 134.
Mishra, V. K., Shrivastava, M. K., Raizada, R. B (1998) Testicular toxicity in rat to repeated oral administration of tetramethyl thiuram disulfide (Thiram). Ind. J. Exptl. Biol., 36, 390-394.
Murphy, S. D. and Porter, S. (1966) Effects of toxic chemicals on some adaptive liver enzymes, liver glycogen and blood glucose in fuster rats. Biochem. Pharmacol., 15, 1655- 1676.
Nachles, M. M. Margulius, S. I. and Sellirgman, A.M(1960) Site of electron transfer to tetrazolium salts in the succinoxidase. J. Biol. Chem., 235, 2739.
Nagoha, E. O., Akanji, M. A. and Madusolumo, M. A(1989) Studies on correlations between Chloroquine induced tissue damage and serum enzyme changes Ksheerasagar and Kaliwal 75 in the rat. Experentia, 45, 143-146.
Nebbia, C. and Ferrero, E. (1991) Pathologic changes tissue distribution and extent of common to ETU after sub acute administrations of zinc ethylene bisdithiocarbamate to calves with immature lumen function. Am. J. Vet. Res., 52, 1717-1722.
Pala, I., Vig., P. J. S., Desaiah, D. and Srinivasan, A(1991) In vitro effects of organophosphorus compounds on calmodulin activity. J. Appl. Toxicol., 11 (6), 391- 395.
Plaa, G. L. (1986) Toxic response of the liver In: Klaassen C. D., Amdur M. O., Doull, J. (eds) Casarett and Doull’s toxicology, the basic science of poisons, 3rd edn. MacMillan Publishing Company, New York, pp. 310- 329.
Rao, C. V. and Banerji, S. A. (1990) Effect of feeding polychlorinated biphenyl (Aroclor 1260) on hepatic enzymes in rats. Ind. J. Exptl. Biol., 28, 149-151.
Renzi, B. E., Krieger, P. I. (1986) Sub- lethal acute toxicity of carbosulfan [2, 3- dihydro2, 2-dimethyl- 7 benzofuranyl (di-nbutylaminosulfenyl) methyl carbamate] in the rat after intravenous and oral exposure. Fundam. Appl. Toxicol., 6, 7-15.
Richardson, R. J. (1981) Toxicology of the nervous system. In: Toxicology principles and practice, A. L. Reeves (Ed), Wiley Inter Science Publishers, Toronto.
Schneider, W. C. (1957) Determination of nucleic acids in tissues by pentose analysis. In: Colowick, S .P., Kaplan , N. D. (eds) Methods in Enzymology, New York, Academic Press, pp. 680-684.
Shakoori, A. R., Ali, S. S. and Saleem, M. A. (1988) Effects of six month feeding of cyper methrin on the blood and liver of albino rats. J. Biochem. Toxicol., 3, 59-11.
Shivanandappa, T. and Krishnakumari, M. K. (1981) Histochemical and biochemical change sin rats fed dietary benzene hexachloride. Ind. J. Exptl. Biol., 19, 1163- 1168.
Siddiqui, M. K. J., Anjum, F. and Qudri, S. S. H. (1987) Some metabolic changes induced by endosulfan in hepatic and extra hepatic tissues of rat. J. Environ. Sci., 22, 553-564.
Siddiqui, M. K. J., Anjum, F., Mahboob, M., and Mustafa, M. (1991) Effects of dimethoate on hepatic cytochrome P-450 and glutathione S-transferase activity in pigeon and rat. Ind. J. Expt. Biol., 29, 1071- 1073.
Snow, D. H. and Watson, A. D. (1973) The acute toxicity of dichlorvos in the dog. Aust. Vet. J., 49,113 119. Shrivastava, A. K., Raina, R., Choudhary, R.K. and Malik, T.K. (1989) The acute toxicity and Bioehcmial alterations in rats after single oral exposure to dichlorvos. Pesticides, 2, 35-40.
Shrivastava, A. K., Gupta, B. N., Mathur, A. K., Mathur, N., Mahendra, P. N., Bharti, R. S. (1991)The clinical and biochemical study of pesticide sprayers. Hum. Exp. Toxicol., 10, 279-283.
Stott, Ian, Anupam, M., Alex, R., Norman, W. T. and Jeffrey, R. F. (1997)Low dose ithiocarbamate attenuates the hepatotoxicity of 1, 3- dichloro- 2- propanol and selectivity inhibits CYP2E1 activity in the rat. Human Expt. Toxicol., 16, 262-266.
Swamy, K. V., Ravikumar, R. and Murali Mohan, P. (1992) Effect of chronic sub lethal daily dosing of monocrotophos on some aspects of protein metabolism in rat brain. Bull. Environ. Contam. Toxicol., 49, 723-729.
Topktas, M., Renci Zogullari, E., Ila, H. B. (1996) In vivo chromosomal aberrations in bone marrow cells of rats with marshal. Myt. Res., 371, 259-264.
Walter, Z., czakowska, A. and Lipecka, K. (1980) Effect of malathion on the genetic material of human lymphocytes stimulated by phytohemagglutinin (PHA). Human Genet., 53, 375-381.
Worblewski, F. and La Due, J.S(1955) Serum glutamic oxaloacetic transaminase activity as index of liver cell injury. A preliminary report. Ann. Inter. Medicine, 43, 345.
Yatzidis, S. H. (1960) Measurement of transaminases in serum. Nature, 186 (4718), 79-80.
Zarh, J. A., Bruschweiler, B. J. and Schlatler, J. R(2002) Azole fungicides affect mammalian steroidogenesis by inhibiting sterol 14αdemethylase and aromatase. Environ. Health. Perspect., 111, 255-261.
Zelesco, P. A., Barbieri, I. and Graves, J. A. M(1990) Use of a cell hybrid test system to demonstrate that Benomyl induces aneuploidy and polyploidy. Mut. Res., 242, 329-335