The aim of this study was to evaluate the effect of carbofuran on the levels of certain biomarkers in heart of rat exposed to sublethal concentrations of pesticide for 30 days after each interval of 24？h. The ameliorative effect of vitamin C by pretreatment of rats was also monitored. The results indicated that the activities of acetylcholinesterase and lactate dehydrogenase (LDH) decreased significantly in rat heart tissues, the extent of inhibition being concentration dependent. In contrast, the level of LDH increased in serum. The levels of malondialdehyde, total thiols, and glutathione were significantly elevated whereas the activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione-S-transferase were remarkably decreased in rat heart tissues. The serum concentrations of cholesterol increased by 47 and 77% and high density lipids decreased by 35 and 64%, respectively, due to exposure to 5 and 10% LD50 of carbofuran. The prior treatment of rats with vitamin C (100？mg？kg？1 body weight) exerted significant ameliorative effect. The recovery was higher at low carbofuran concentration (5%) tested. The results indicated that carbofuran induced oxidative stress and caused damage to cardiac tissues, which could be recovered by prior application of vitamin C. 1. Introduction The pesticides have been widely used since past few decades to improve the yield of agricultural and forestry plant products. It is also used to protect the industry and household items. The use of pesticide is not specific which may lead to number of toxicological consequences to the environmental components [1]. The lower toxicity and lesser environmental persistence of organocarbamates have led their application more frequent than any other pesticide such as organophosphate (OP), organochlorines (OCl). The OP pesticides inactivate acetylcholinesterase (AChE) via irreversible ester bond formation with hydroxyl group of serine residue present at the active site of enzyme. AChE is responsible for hydrolyzing the neurotransmitter, acetylcholine (ACh), in central as well as in peripheral nervous systems [2]. The mechanism of action of organochlorine pesticides such as lindane ( -hexachlorocyclohexane) is hyperexcitability [3] by both stimulating the synaptic transmission and suppressing the GABA-activated chloride current by interacting with the receptor GABA-chloride channel complex [4]. The organocarbamate pesticides cause reversible inhibition of AChE by carbamylation of serine residue of AChE. The inhibition is therefore short lived. Thus, it causes
References
[1]
D. Milatovic, R. C. Gupta, and M. Aschner, “Anticholinesterase toxicity and oxidative stress,” TheScientificWorldJournal, vol. 6, pp. 295–310, 2006.
[2]
A. Agrawal and B. Sharma, “Pesticides induced oxidative stress in mammalian systems: a review,” International Journal of Biological and Medical Research, vol. 1, no. 3, pp. 90–104, 2010.
[3]
R. K. Loch-Caruso, K. A. Criswell, C. M. Grindatti, and K. A. Brant, “Sustained inhibition of rat myometrial gap junctions and contractions by lindane,” Reproductive Biology and Endocrinology, vol. 1, p. 62, 2003.
[4]
M. Sauviat, A. Colas, and N. Pages, “Does lindane (gamma-hexachlorocyclohexane) increase the rapid delayed rectifier outward K+ current (IKr) in frog atrial myocytes?” BMC Pharmacology, vol. 2, p. 15, 2002.
[5]
M. Kaur and R. Sandhir, “Comparative effects of acute and chronic carbofuran exposure on oxidative stress and drug-metabolizing enzymes in liver,” Drug and Chemical Toxicology, vol. 29, no. 4, pp. 415–421, 2006.
[6]
R. C. Gupta, “Carbofuran toxicity,” Journal of Toxicology and Environmental Health, vol. 43, no. 4, pp. 383–418, 1994.
[7]
J. Rendón-Von Osten, A. M. V. M. Soares, and L. Guilhermino, “Black-bellied whistling duck (Dendrocygna autumnalis) brain cholinesterase characterization and diagnosis of anticholinesterase pesticide exposure in wild populations from Mexico,” Environmental Toxicology and Chemistry, vol. 24, no. 2, pp. 313–317, 2005.
[8]
R. M. Whyatt, D. B. Barr, D. E. Camann et al., “Contemporary-use pesticide in personal air samples during pregnancy and blood samples at delivery among urban minority mothers and newborns,” Environmental Health Perspectives, vol. 111, no. 5, pp. 749–756, 2003.
[9]
D. K. Rai, P. K. Rai, S. I. Rizvi, G. Watal, and B. Sharma, “Carbofuran-induced toxicity in rats: protective role of vitamin C,” Experimental and Toxicologic Pathology, vol. 61, no. 6, pp. 531–535, 2009.
[10]
D. K. Rai, R. K. Sharma, P. K. Rai, G. Watal, and B. Sharma, “Role of aqueous extract of Cynodon dactylon in prevention of carbofuran-induced oxidative stress and acetylcholinesterase inhibition in rat brain,” Cellular and Molecular Biology, vol. 57, no. 1, pp. 135–142, 2011.
[11]
Z. P. Yang and W. Dettbarn, “Diisopropylphosphorofluoridate-induced cholinergic hyperactivity and lipid peroxidation,” Toxicology and Applied Pharmacology, vol. 138, no. 1, pp. 48–53, 1996.
[12]
J. N. Keller, R. J. Mark, A. J. Bruce et al., “4-hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes,” Neuroscience, vol. 80, no. 3, pp. 685–696, 1997.
[13]
R. J. Mark, Z. Pang, J. W. Geddes, K. Uchida, and M. P. Mattson, “Amyloid β-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipid peroxidation,” Journal of Neuroscience, vol. 17, no. 3, pp. 1046–1054, 1997.
[14]
A. Kamboj, R. Kiran, and R. Sandhir, “N-Acetylcysteine ameliorates carbofuraninduced alterations in lipid composition and activity of membrane bound enzymes,” Molecular and Cellular Biochemistry, vol. 286, no. 1-2, pp. 107–114, 2006.
[15]
S. Padilla, R. S. Marshall, D. L. Hunter, and A. Lowit, “Time course of cholinesterase inhibition in adult rats treated acutely with carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur,” Toxicology and Applied Pharmacology, vol. 219, no. 2-3, pp. 202–209, 2007.
[16]
D. K. Rai and B. Sharma, “Carbofuran-induced oxidative stress in mammalian brain,” Molecular Biotechnology, vol. 37, no. 1, pp. 66–71, 2007.
[17]
B. Kaur, A. Khera, and R. Sandhir, “Attenuation of cellular antioxidant defense mechanisms in kidney of rats intoxicated with carbofuran,” Journal of Biochemical and Molecular Toxicology, vol. 26, no. 10, pp. 393–398, 2012.
[18]
R. K. Sharma and B. Sharma, “In-Vitro carbofuran induced genotoxicity in human lymphocytes and its mitigation by vitamins C and E,” Disease Markers, vol. 32, no. 3, pp. 153–163, 2012.
[19]
S. Srinivasan and L. Pari, “Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats,” Chemico-Biological Interactions, vol. 195, no. 1, pp. 43–51, 2012.
[20]
H. Fetoui, M. Makni, E. Mouldi Garoui, and N. Zeghal, “Toxic effects of lambda-cyhalothrin, a synthetic pyrethroid pesticide, on the rat kidney: involvement of oxidative stress and protective role of ascorbic acid,” Experimental and Toxicologic Pathology, vol. 62, no. 6, pp. 593–599, 2010.
[21]
J. H. Doroshow, G. Y. Locker, and C. E. Myers, “Enzymatic defenses of the mouse heart against reactive oxygen metabolites. Alterations produced by doxorubicin,” Journal of Clinical Investigation, vol. 65, no. 1, pp. 128–135, 1980.
[22]
G. L. Ellman, K. D. Courtney, V. Andres Jr., and R. M. Featherstone, “A new and rapid colorimetric determination of acetylcholinesterase activity,” Biochemical Pharmacology, vol. 7, no. 2, pp. 88–95, 1961.
[23]
B. L. Horecker and A. Kornberg, “The extinction coefficient of the reduced band of pyridine nucleotides,” Journal of Biological Chemistry, vol. 175, pp. 385–390, 1948.
[24]
A. Zlatkis, B. Zak, and A. J. Boyle, “A new method for the direct determination of serum cholesterol,” The Journal of Laboratory and Clinical Medicine, vol. 41, no. 3, pp. 486–492, 1953.
[25]
M. F. Lopes Virella, P. Stone, S. Ellis, and J. A. Colwell, “Cholesterol determination in high density lipoproteins separated by three different methods,” Clinical Chemistry, vol. 23, no. 5, pp. 882–884, 1977.
[26]
W. G. Niehaus Jr. and B. Samuelsson, “Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation,” European Journal of Biochemistry, vol. 6, no. 1, pp. 126–130, 1968.
[27]
S. Marklund and G. Marklund, “Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase,” European Journal of Biochemistry, vol. 47, no. 3, pp. 469–474, 1974.
[28]
R. F. Beers Jr. and I. W. Sizer, “A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase,” The Journal of Biological Chemistry, vol. 195, no. 1, pp. 133–140, 1952.
[29]
W. H. Habig, M. J. Pabst, and W. B. Jakoby, “Glutathione S transferases. The first enzymatic step in mercapturic acid formation,” Journal of Biological Chemistry, vol. 249, no. 22, pp. 7130–7139, 1974.
[30]
J. Sedlak and R. H. Lindsay, “Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent,” Analytical Biochemistry C, vol. 25, pp. 192–205, 1968.
[31]
O. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randel, “Protein measurement with the Folin phenol reagent,” The Journal of Biological Chemistry, vol. 193, no. 1, pp. 265–275, 1951.
[32]
R. K. Sharma, S. K. Jaiswal, N. J. Siddiqi, and B. Sharma, “Effect of carbofuran on some biochemical indices of human erythrocytes in vitro,” Cellular & Molecular Biology, vol. 58, no. 1, pp. 103–109, 2012.
[33]
Y. Tonomura, Y. Mori, M. Torii, and T. Uehara, “Evaluation of the usefulness of biomarkers for cardiac and skeletal myotoxicity in rats,” Toxicology, vol. 266, no. 1–3, pp. 48–54, 2009.
[34]
B. M. Razavi, H. Hosseinzadeh, A. R. Movassaghi, M. Imenshahidi, and K. Abnous, “Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure,” Chemico-Biological Interaction, vol. 203, no. 3, pp. 547–555, 2013.
[35]
R. C. Gupta, J. T. Goad, and W. L. Kadel, “In vivo alterations in lactate dehydrogenase (LDH) and LDH isoenzymes patterns by acute carbofuran intoxication,” Archives of Environmental Contamination and Toxicology, vol. 21, no. 2, pp. 263–269, 1991.
[36]
A. Ogutcu, M. Uzunhisarcikli, S. Kalender, D. Durak, F. Bayrakdar, and Y. Kalender, “The effects of organophosphate insecticide diazinon on malondialdehyde levels and myocardial cells in rat heart tissue and protective role of vitamin E,” Pesticide Biochemistry and Physiology, vol. 86, no. 2, pp. 93–98, 2006.
[37]
R. Ananya, S. Subeena, D. A. Kumar, D. T. Kumar, and M. S. Kumar, “Oxidative stress and histopathological changes in the heart following oral lindane (gamma hexachlorohexane) administration in rats,” Medical Science Monitor, vol. 11, no. 9, pp. BR325–BR329, 2005.
[38]
I. A. Zervos, E. Nikolaidis, S. N. Lavrentiadou et al., “Endosulfan-induced lipid peroxidation in rat brain and its effect on t-PA and PAI-1:Ameliorating effect of vitamins C and E,” Journal of Toxicological Sciences, vol. 36, no. 4, pp. 423–433, 2011.
[39]
D. S. Cassarino and J. P. Bennett Jr., “An evaluation of the role of mitochondria in neurodegenerative diseases: mitochondrial mutations and oxidative pathology, protective nuclear responses, and cell death in neurodegeneration,” Brain Research Reviews, vol. 29, no. 1, pp. 1–25, 1999.
[40]
T. Yavuz, N. Delibas, B. Yildirim et al., “Vascular wall damage in rats induced by organophosphorus insecticide methidathion,” Toxicology Letters, vol. 155, no. 1, pp. 59–64, 2005.
[41]
D. Milatovic, R. C. Gupta, A. Dekundy, T. J. Montine, and W. Dettbarn, “Carbofuran-induced oxidative stress in slow and fast skeletal muscles: prevention by memantine and atropine,” Toxicology, vol. 208, no. 1, pp. 13–24, 2005.
[42]
D. Milatovic, M. Zivin, R. C. Gupta, and W. Dettbarn, “Alterations in cytochrome c oxidase activity and energy metabolites in response to kainic acid-induced status epilepticus,” Brain Research, vol. 912, no. 1, pp. 67–78, 2001.
[43]
R. C. Gupta, D. Milatovic, and W. D. Dettbarn, “Nitric oxide modulates high-energy phosphates in brain regions of rats intoxicated with diisopropylphosphorofluoridate or carbofuran: prevention by N-tert-butyl-α-phenylnitrone or vitamin E,” Archives of Toxicology, vol. 75, no. 6, pp. 346–356, 2001.
[44]
M. Brunori, A. Giuffrè, P. Sarti, G. Stubauer, and M. T. Wilson, “Nitric oxide and cellular respiration,” Cellular and Molecular Life Sciences, vol. 56, no. 7-8, pp. 549–557, 1999.
[45]
S. Pou, W. S. Pou, D. S. Bredt, S. H. Snyder, and G. M. Rosen, “Generation of superoxide by purified brain nitric oxide synthase,” Journal of Biological Chemistry, vol. 267, no. 34, pp. 24173–24176, 1992.
[46]
V. I. Lushchak, “Glutathione homeostasis and functions: potential targets for medical interventions,” Amino Acids, vol. 2012, Article ID 736837, 26 pages, 2012.
[47]
H. Sies, “Glutathione and its role in cellular functions,” Free Radical Biology and Medicine, vol. 27, no. 9-10, pp. 916–921, 1999.
[48]
R. Dringen, “Metabolism and functions of glutathione in brain,” Progress in Neurobiology, vol. 62, no. 6, pp. 649–671, 2000.
[49]
B. Halliwell, “Reactive oxygen species and the central nervous system,” Journal of Neurochemistry, vol. 59, no. 5, pp. 1609–1623, 1992.
[50]
S. Ozden and B. Alpertunga, “Effects of methiocarb on lipid peroxidation and glutathione level in rat tissues,” Drug and Chemical Toxicology, vol. 33, no. 1, pp. 50–54, 2010.
[51]
B. D. Goldstein, M. G. Rozen, J. C. Quintavalla, and M. A. Amoruso, “Decrease in mouse lung and liver glutathione peroxidase activity and potentiation of the lethal effects of ozone and paraquat by the superoxide dismutase inhibitor diethyldithio-carbamate,” Biochemical Pharmacology, vol. 28, no. 1, pp. 27–30, 1979.
[52]
F. M. El-Demerdash, “Oxidative stress and hepatotoxicity induced by synthetic pyrethroids-organophosphate insecticides mixture in rat,” Journal of Environmental Science and Health C, vol. 29, no. 2, pp. 145–158, 2011.
[53]
D. K. Rai, P. K. Rai, A. Gupta, G. Watal, and B. Sharma, “Cartap and carbofuran induced alterations in serum lipid profile of Wistar rats,” Indian Journal of Clinical Biochemistry, vol. 24, no. 2, pp. 198–201, 2009.
[54]
M. I. Yousef, F. M. El-Demerdash, and F. M. E. Radwan, “Sodium arsenite induced biochemical perturbations in rats: ameliorating effect of curcumin,” Food and Chemical Toxicology, vol. 46, no. 11, pp. 3506–3511, 2008.
[55]
E. N. Frankel, “Antioxidants in lipid foods and their impact on food quality,” Food Chemistry, vol. 57, no. 1, pp. 51–55, 1996.
[56]
D. Chandra, U. N. Tripathi, S. Srivastava, and A. Swaroop, “Carbofuran induced biochemical toxicity in mice: protective role of Momordica charantia,” European Journal of Experimental Biology, vol. 1, no. 1, pp. 106–112, 2011.
