As an index of lipid peroxidation (LPO), levels of thiobarbituric acid (TBA)-reactive substances were examined in the kidneys of male F344 rats, BDF1, CDF1, and B6C3F1 mice, and Syrian golden hamsters after a single intravenous (IV) administration of potassium bromate (KBrO3) at various doses. In the rats, LPO levels were significantly increased in both a dose-dependent and time-dependent manner. However, when the rats were given intraperitoneal (IP) injection of cysteine, the levels of LPO were not significantly different between KBrO3-treated animals and controls. In CDF1 mice, the slight increases in LPO levels observed were much weaker and not statistically significant. On the other hand, treatment of BDF1 and B6C3F1 mice or hamsters with KBrO3 resulted in decreased values as compared to controls. The effect of treatment with cysteine, glutathione (GSH), or diethyl maleate (DEM) on mortality was tested in male F344 rats given IV injection of KBrO3 at various doses. Significant reduction and elevation in the mortality were observed in rats treated with cysteine or GSH and DEM, respectively. Significant dose-dependent and time-dependent increases were observed in the levels of serum non-protein nitrogen (NPN), blood urea nitrogen (BUN), and creatinine, and absolute and relative weight of the kidneys in male F344 rats administered KBrO3 IV. Microscopically, the appearance of numerous eosinophilic droplets in the cytoplasm of proximal tubular epithelium of KBrO3-treated rats was noteworthy. All these changes were reduced and exacerbated by treatment with cysteine or GSH and DEM, respectively. The possibility of LPO formation in the kidney by active oxygen radicals generated by KBrO3 is suggested. A possible relationship between LPO levels in the kidney and species differences in the renal toxicity and carcinogenicity of KBrO3 is implicated.
Dose-Dependent Renal Tubular Toxicity of Harman and Norharman in Male F344 Rats
