Antagonism by chloramphenicol of carbon tetrachloride hepatotoxicity. Examination of microsomal cytochrome P-450 and lipid peroxidation.

Administration of chloramphenicol early in Ccl, intoxication prevents lipid peroxidation of endoplasmic reticulum membranes. Conversely, a sulfamoyl analog, Tevenel, was ineffective in preventing the lipoperoxidative process. Likewise, in an in vitro microsomal system chloramphenicol inhibited a lipid peroxidation process and Tevenel did not. However, both compounds bind to cytochrome P-450. Chloramphenicol did not maintain cytochrome P-450 levels after Ccl, administration nor did it depress cytochrome P-450 levels in untreated animals. The data obtained indicate that chloramphenicol may prevent lipid peroxidation either by inhibiting Ccl, metabolism or by acting as a free radical sequestering agent.