THE INTERACTIONS BETWEEN RETINOL AND 5 DIFFERENT HEPATOTOXICANTS IN THE SWISS WEBSTER MOUSE

The interactive effects between retinol and various hepatotoxicants (a llyl alcohol, acetaminophen, carbon tetrachloride, D-galactosamine, an d phalloidin) were studied in the male Swiss Webster mouse. The mice w ere administered retinol at 75 mg/kg/day (or the vehicle of retinol) b y oral gavage for 7 days. Hepatoxicity produced by the chemicals was d etermined by plasma alanine aminotransferase (ALT) activity and histop athology. After 7 days of retinol pretreatment, the hepatotoxicities o f allyl alcohol, acetaminophen, and galactosamine were potentiated. In terestingly, the hepatotoxicity of carbon tetrachloride and phalloidin was protected by identical retinol pretreatment. Microscopic examinat ion of histologic liver sections demonstrated the specific hepatic nec rosis associated with each individual chemical and confirmed the ALT v alues obtained. Once an interaction between retinol and the five hepat otoxicants was established, the duration of retinol pretreatment neces sary to elicit an interaction was determined for each hepatotoxicant. Results demonstrated that the duration of retinol pretreatment was spe cific for each hepatotoxicant. The accumulation of retinoids in the li ver during retinol pretreatment was determined using high-performance liquid chromatography analysis. Significant increases in the basal liv er levels of retinol and retinyl palmitate were seen within 1 to 3 day s of retinol treatment compared to control. Retinol pretreatment resul ted in potentiation or protection of specific hepatotoxicant-induced l iver damage. Currently, studies are being conducted which probe into t he mechanisms of these interactions. (C) 1995 Society of Toxicology.