Nephrotoxicity induced by long-term administration of paraquat in rats: protective effects of quercetin and extracts of malt and green tea

ABSTRACT

Paraquat [PQ], a well-known herbicide, causes nephrotoxicity mediate by redox-cycling and extensive production of superoxide anions in the kidney. The possible protective effects of three natural products namely; green tea extract [I mg/kg], malt extract [625 mg/kg] and quercetin [50 mg/kg], against nephrotoxicity induced by long-term administration of PQ in rats were examined. PQ was intraperitoneally injected once weekly [20 mg/kg] with or without oral daily treatment with any of the three agents for 6 consecutive weeks. Nephrotoxicity was assessed by measuring serum creatinine level, histological examination of kidney sections and calculation of percentage kidney-to-body weight of rats. In addition changes in enzymatic activities of superoxide dismutase [SOD], lactate dehydrogenase [LDH] and myeloperoxidase [MPO], as well as reduced glutathione [GSH], protein thiols [Pr-SHs] and total nitrate/nitrite [NOx] contents of renal tissues were determined. Renal lipid peroxidation was also assessed by measurement of the levels of thiobarbituric acid reactive substances [TBARS]. PQ administration resulted in marked nephrotoxicity manifested by severe increase in serum creatinine level accompanied by changes in renal oxidant status of rats demonstrated by elevated TBARS level and increased activities of MPO and SOD. PQ also resulted in depletion of renal GSH and NOx contents as well as reduced activity of cytosolic LDH. On the other hand, no significant effect was noted on percentage kidney-to-body weight of rats or on renal Pr-SHs contents. Six weeks of regular daily treatment with any of the chosen agents significantly protected against most of PQ-induced biochemical changes. Histological examinations of kidney morphological changes revealed marked lesions with PQ especially in renal proximal tubules and variable degrees of protection by the test agents with the best results produced by malt extract and quercetin and to lesser extent by green tea extract. It could be concluded that malt extract and quercetin offered remarkable protection against PQ-induced nephrotoxicity in rats. Green tea extract produced some beneficial effects on the biochemical events associated with PQ-induced nephrotoxi city