ANTAGONISM BY CHLORAMPHENICOL OF CARBON-TETRACHLORIDE HEPATOTOXICITY - EXAMINATION OF MICROSOMAL CYTOCHROME-P-450 AND LIPID PEROXIDATION

Administration of chloramphenicol early in CCl4 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 CCl4 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 CCl4 metabolism or by acting as a free radical sequestering agent. © 1978.