Pathogenesis of ochratoxin A induced nephropathy in rats with special reference to oxidative damage, cytokine profile and ultrastructural changes
Ochratoxin A (OTA), a food contaminant and potent nephrotoxin, adversely affects human and animal health. The nephropathic effects of subchronic exposure to OTA (given @ 0.25 mg and 0.50 mg OTA/kg body weight, daily for four weeks) were investigated in seven-weeks old male Wistar rats. The pathological changes in kidneys were studied at intervals of 2 days and 1,2, 3 and 4 weeks of OTA treatment. In general, clinical condition, body weight, biochemical parameters and kidneys were adversely affected, being more severe in the higher dose group. Higher dose group rats exhibited clinical signs of weakness, anorexia, increased water intake and reduced body weight gain. Serum total proteins were decreased, and serum creatinine and LDH levels were increased. SDS-PAGE analysis showed increased excretion of high molecular weight proteins in the urine of high dose group rats. Kidneys of OTA-treated rats showed increased oxidative damage as evidenced by elevated catalase, superoxide dismutase and malondialdehyde levels. Histopathological and ultrastructural changes were characterised by severe degenerative changes especially in the proximal convoluted tubules (PCTs) with significant mitochondrial changes and formation of myelin figures in the epithelial cells of PCTs. The levels of various cytokines viz., IFN-y IL-2 and IL-4 in the spleen and Peyer's patches were found increased with the progression of ochratoxicosis. It was concluded that subchronic, non-lethal levels of OTA induced severe nephrotoxicity with significant histopathological and ultrastructural changes, which could be attributed to oxidative damage and cytokine alterations in the target tissues.
Cytokines, Electron microscopy, Histopathology, Mycotoxins, Nephropathy, Ochratoxin A, Oxidative damage.