BILIARY EXCRETORY DYSFUNCTION FOLLOWING EXPOSURE TO PHOTOMIREX AND PHOTOMIREX-CARBON TETRACHLORIDE COMBINATION

Exposure of male rats to 50 and 150 ppm of photomirex in the diet for 15 days resulted in impaired biliary excretory function, decreased hepatic mitochondrial oligomycin-sensitive Mg2+-ATPase (MATPase) activity and liver hypertrophy accompanied by lipid accumulation. Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) were unaffected. Biliary excretion of intravenously administered polar metabolites of imipramine (PMIMP) and phenolphthalein glucuronide (PG) was reduced 21% and 23%, respectively, at 50 ppm photomirex and 28 and 31%, respectively at 150 ppm photomirex. MATPase activity was inhibited 25% and 36% at 50 and 150 ppm photomirex. The effect of preexposure to 50 ppm photomirex on carbon tetrachloride (CCl4) hepatotoxicity was also investigated. Treatment of animals on control diet with CCl4 (0.1 ml/kg, i.p.) alone 24 h prior to the test, resulted in a 25% decrease in the biliary excretion of PG. Treatment with 50 ppm photomirex prior to CCl4, resulted in 40% reduction of PG excretion. Liver weight, SGOT and SGPT were unaffected by the CC14 challenge alone, while it did produce slight centrilobular necrosis. The photomirex/CCl4 interaction resulted in liver hypertrophy, 7- and 8-fold elevations in SGOT and SGPT, and considerable centrilobular necrosis. Bile flow was not significantly affected by any of the above treatments. These results indicate that photomirex-induced hepatobiliary dysfunction may bear a relationship to the inhibition of MATPase activity and preexposure to photomirex does potentiate CCl4 hepatotoxicity. © 1979 Elsevier/North-Holland Scientific Publishers, Ltd.