INVOLVEMENT OF MAIN OXIDATIVE STRESS MECHANISMS IN THE TOXICITY OF BENOMYL AND CARBENDAZIM IN RATS

Abstract

This study aimed to evaluate the role of oxidative stress in toxicity induced by BNL (benomyl) and its metabolite CBZ (carbendazim), which are systemic broad-spectrum benzimidazole fungicides.The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), γ−glutamyl transpeptidase (GGT) and glutathione-S-transferase (GST) as well as the levels of malonyldialdehyde (MDA), being a lipid peroxidation marker and reduced glutathione (GSH) were measured in the liver, kidney, testis and brain tissues of the rats, after acute exposure of the two fungicides and their mixture.In all tissues, it was observed that MDA levels were increased and changes in antioxidant defense system were occurred. The induction of oxidative stress manifested as changes in the activity and/or levels of antioxidative parameters has been suggested as the mechanism by which BNL and CBZ induces their toxic effects. *Correspondence: [e-mail]

Keywords

• Oxidative Stress, Benomyl, Carbendazim, Pesticide toxicity

INVOLVEMENT OF MAIN OXIDATIVE STRESS MECHANISMS IN THE TOXICITY OF BENOMYL AND CARBENDAZIM IN RATS

Abstract

Bu çalışmada, geniş spektrumlu sistemik benzimidazol grubu fungusidlerden olan BNL (benomyl) ve metaboliti CBZ (carbendazim)’ nin toksik etki mekanizmalarında oksidatif stresin rolü araştırıldı. BNL, CBZ ve karışımlarına akut maruziyet sonrası sıçanların karaciğer, böbrek, testis ve beyin dokularında oksidatif stres göstergesi olarak lipid peroksidasyon son ürünü malondialdehid (MDA) ve indirgenmiş glutatyon (GSH) seviyeleri, süperoksid dismutaz (SOD), katalaz (CAT), glutatyon peroksidaz (GSHPx), glutatyon redüktaz (GSH-Rd), gama glutamil transpeptidaz (GGT) ve glutatyon-S-transferaz (GST) antioksidan enzim aktivitelerinin tayini yapıldı. Tüm dokularda MDA düzeylerinin arttığı ve antioksidan savunma sistemlerinde değişiklik olduğu gözlendi. BNL ve CBZ’nin toksisitesinde, antioksidan parametrelerin aktivite ve/veya düzeylerinde oksidatif stresin indüksiyonu sonucu görülen değişikliklerin rol oynadığı sonucuna varıldı.

References

1. Davidse LC. Annu Rev Phytopathol, 24, 43-65 (1986).
2. Benomyl, IPCS, International Programme on Chemical Safety. Health and Safety Guide No.81, World Health Organization, Geneva, 1993.
3. Carbendazim, IPCS, International Programme on Chemical Safety. Health and Safety Guide No.82, World Health Organization, Geneva, 19 Hess RA., Nakai M., Histol Histopathol., 15, 207-224 (2000).
4. Davidse LC., Flach W., J Cell Biol., 72, 174-193 (1977).
5. Russell GJ., Gill JH., Lacey E., Biochem Pharmacol., 43, 1095-1100 (1992).
6. Nakai M., Hess RA., Moore BJ., Guttroff RF., Strader LF., Linder RE., J Androl., 13, 507-518 (1992).
7. McCarroll NE., Protzel A., Ioannou Y., Frank Stack HF., Jackson MA., Dearfield KL., Mutat Res., 512, 1-35 (2002).
8. Pratibha R., Sameer R., Padmanabh VR.,Rataboli DA., Bhiwgade DA., Dhume CY., Eur J Pharmacol., 532, 290-293 (2006).

9. Sharma Y., Bashir S., Irshad M., Gupta DS., Dogra TD., Toxicology., 206, 49-57 (2005).
10. Brocardo PS., Pandolfo P., Takahashi RN., Rodrigues AL., Dafre AL., Toxicology., 207, 283-291 (2005).
11. Maran E., Fernandez M., Barbieri P., Font G., Ruiz MJ., Ecotoxicol Environ Saf., 72, 922-930 (2009).
12. Abdollahi M., Ranjbar A., Shadnia S., Nikfar S., Rezaie A., Med Sci Monit., 10, 141-147 (2004).
13. Ozden S., Alpertunga B., Drug Chem Toxicol., 33, 50-54 (2009).
14. Halliwell B., Gutteridge J.M.C., Free Radicals in Biology and Medicine. 5 th ed., p.268-340, University Press, Oxford (2007).
15. Sutcu R., Altuntas I., Buyukvanli B., Akturka O., Koylu H., Delibas N., Toxicol Ind Health., 23, 13-17 (2007).
16. Celik I., Suzek H., Food Chem Toxicol., 46, 2796-2801 (2008).
17. Karademir Catalgol B., Ozden S., Alpertunga B., Toxicol in vitro, 21, 1538-1544 (2007).
18. Goel A., Dani V., Dhawan DK., Chem Biol Interact., 156, 131-140 (2005).
19. Beuret CJ., Zirulnik F., Gimenez MS., Reprod Toxicol., 19, 501-504 (2005). Catalgol B., Grune T., Curr Pharm Des., 15, 3043-3051 (2009).
20. Mates JM., Toxicology., 153, 83-104 (2000).
21. Beuge JA., Aust SD., Method Enzymol., 52, 302-310 (1978).
22. Draper HH., Hadley M., Method Enzymol., 186, 421-431 (1990).
23. Beutler E., Red cell metabolism. A Manual of Biochemical Methods. 3th ed. Grune & Stratton, New York (1975).
24. Sun Y., Oberley LW., Li Y., Clin Chem., 34, 497-500 (1988).
25. Aebi H., Method Enzymol., 105, 121-126 (1984).
26. Pleban PA., Munyani A., Beachum J., Clin Chem., 28, 311-316 (1982). Carlberg I., Mannervik B., Method Enzymol., 113, 484 – 490 (1985).
27. Habig WH., Pabst JM., Jakoby WB., J Biol Chem 249, 7130-7139 (1974). Tate SS., Meister A., J Biol Chem., 249, 7593-7602 (1974).
28. Lowry OH., Rosebrough NJ., Farr AL., Randall RJ et al. J Biol Chem., 193, 265-275 (1951).
29. Altuntas I., Delibas N., Sutcu R., Hum Exp Toxicol., 21, 681-685 (2002). Yavuz T., Altuntas I., Delibas N., Yildirim B., Candir O., ora A., Karahan N., Ibrisim E., Kutsal A., Hum Exp Toxicol., 23, 323-329 (2004).
30. Kalender S., Kalender Y., Ogutcu A., Uzunhisarcikli M., Durak D., Acikgoz F., Toxicology., 202, 227-235 (2004).
31. John S., Kale M., Rathore N., Bhatnagar D., J Nutr Biochem., 12, 500-4 (2001).
32. Giray B., Gurbay A., Hincal F., Toxicol Lett., 118, 139-146 (2001).
33. Prasamthi K., Muralidhara Rajini PS., Food Chem Toxicol., 43, 299-306 (2005).
34. Kamboj A., Kiran R., Sandhir R., Exp Brain Res., 170, 567-575 (2006). Seth V., Banerjee BD., Chakravorty AK., Pestis Biochem Physiol., 71, 133-139 (2001).
35. Ozden S., Catalgol B., Gezginci-Oktayoglu S., Arda Pirincci P., Bolkent S., Alpertunga B., Food Chem Toxicol., 47, 1676-1684 (2009).
36. Dewa Y., Nishimura J., Muguruma M., Maksumoto S., Takahashi M., Jin M., Mitsumori K., Arch Toxicol., 81, 647-654 (2007).
37. Dewa Y., Nishimura J., Muguruma M., Jin M., Kawai M., Saegusa Y., Arch Toxicol., 83, 503-511 (2009).
38. Locatelli C., Pedrosa PC., De Bem AF., Creczynski-Pasa TB., Cordova CA., Wilhelm-Filho D., Redox Rep., 9, 89-95 (2004).
39. Karatas F., Servi S., Kara H., Kiran TR., Saydam S., Biol Trace Elem Res., 126, 214-221 (2008).
40. Saber AK., Shalaby SY., Toxicol. Environ. Health Contam Toxicol., 17, 1-9 (2012).
41. Prashantkumar W., Saini S.P.S., Rampal S., Prakash N., Lokesh LV., Toxicol. Environ. Chem., 95, 330-336 (2013).
42. Daiber A., Oelze M., Coldewey M., Bachschmid M., Wenzel P., Sydow K., Wendt M., Kleschyov AL., Stalleicken D., Ullrich V., Mülsch A., Münzel T., Mol Pharmacol., 66, 1372-1382 (2004).
43. Wang XF., Li S., Chou AP., Bronstein JM., Neurobiol Dis., 23, 198-205 (2006).
44. Lodovici M., Aiolli S., Monserrat C., Dolara P., Medica A., Di Simplicio P., J Environ Pathol Toxicol Oncol., 13, 163-168 (1994).
45. De Mejia EG., Ramirez-Mares MV., Nair MG., J Agric Food Chem., 50, 7714-7719 (2002).
46. Urani C., Chiesara E., Galvani P., Marabini L., Santagostino A., Camatini M., Toxicol Lett., 76, 135-144 (1995)
47. Muthuviveganandavel V., Muthuraman P., Muthu S., Srikumar K., J Toxicol Sci., 33, 25-30 (2008).
48. Banks D., Soliman MR., Toxicology, 116, 177-181 (1997).
49. Ramirez-Mares MV., de Mejia EG., Food Chem Toxicol., 41, 1527-1535 (2003).
50. Rajeswary S., Kumaran B., Ilangovan R., Yuvaraj S., Sridhar M., Venkataraman P., Srinivasan N., Aruldhas MM., Reprod Toxicol., 24, 371380 (2007).
51. Hazarika A., Sarkar SN., Hajare S., Kataria M., Malik JK., Toxicology., 185, 1-8 (2003).
52. Khan SM., Sobti RC., Kataria L., Clin Chim Acta., 2005; 358: 131-138. Tuzmen N., Candan N., Kaya E., Demiryas N., Cell Biochem Funct., 26, 119-124 (2008).
53. Khan SM., Cell Biochem Funct., 24, 327-332 (2006).
54. Lim J., Miller MG., Toxicol Appl Pharmacol., 142, 401-410 (1997).
55. Furnes B., Schlenk D., Drug Metab Dispos., 33, 214-218 (2005).
56. Gardiner JA., Kirkland J., Klopping H., J Agric Food Chem., 22, 419427 (1974).
57. Heikkila RE., Cabbat FS., Cohen G., J Biol Chem., 251, 2182-2185 (1976).
58. Dimitrova MS., Tishinova V., Velcheva V., Comp Biochem Physiol C Pharmacol Toxicol Endocrinol., 108, 43-46 (1994).
59. Yousef MI., Awad TI., Mohamed EH., Toxicology, 227, 240-247 (2006). Celik I., Tuluce Y., Isik I., J Biochem Mol Toxicol., 20, 174-182 (2006). Winterbourn CC., Stern A., J Clin Invest., 80, 1486-1491 (1987).
60. Ahmed RS., Seth V., Banerjee BD., Indian J Exp Biol., 38, 604-606 (2000).
61. Banerjee BD., Seth V., Bhattacharya A., Pasha ST., Chakraborty AK., Toxicol Lett., 107, 33-47 (1999).
62. Axness M., Fleeker J., Pestic Biochem Physiol., 11, 1-12 (1979).
63. Brigelius-Flohé R., Free Radic Biol Med., 27, 951-965 (1999).
64. Lee DH., Blomhoff R., Jacobs DR Jr., Free Radic Res., 38, 535-539 (2004).
65. Kono Y., Fridovich I., J Biol Chem., 257, 5751-5754 (1982).
66. Escobar JA., Rubio MA., Lissi EA., Free Radic Biol Med., 20, 285-290 (1996).
67. Choi SW., Benie IF., Collins AR., Hannigan BM., Strain JJ., Mutat Res., 551, 109-117 (2004).