Nephrotoxicity of butylated hydroxytoluene in phenobarbital-pretreated male rats

A single large dose of butylated hydroxytoluene (BHT, 1000 mg/kg) in male Fischer 344 rats produced some renal damage, reduced accumulation of p-aminohippuric acid in renal slices, proteinuria and enzymuria, in addition to hepatic damage. Further, prior administration of phenobarbital (80 mg/kg, i. p., daily for 4 days) in the high-dose BHT-treated male rats produced renal damage accompanied by slight tubular necrosis. The renal damage was confirmed by biochemical and histological changes. These changes were dose dependent, with a maximum at 24 h after BHT administration, but had returned to the normal range by 48 h. Female rats, on the other hand, were less susceptible to BHT-induced renal and hepatic damage than male rats. The results indicate sex differences in BHT-induced renal or hepatic damage.