EFFECT OF THE PYRROLIZIDINE ALKALOID, MONOCROTALINE, ON BILE COMPOSITION OF THE ISOLATED, PERFUSED-RAT-LIVER

Monocrotaline is a hepatotoxic pyrrolizidine alkaloid, releasing high levels of metabolites into bile of isolated, perfused liver. Although perfusion of rat liver with 0.5 mM monocrotaline does not affect bile, flow over a 1 hr study period, it markedly affects bile composition. Biliary release of conjugated and free GSH increases 30-fold. Marked i ncreases are also observed in the biliary concentration of the related sulfur-containing substances, cysteine and cysteinylglycine. However, biliary release of the sulfur amino acids, taurine and methionine, is unaffected. Only two amino acids show mildly increased releases, 23% for glycine and 46% for aspartate. Release of bile acids, cholesterol and phospholipids also decrease both in terms of mM concentration in b ile and in terms of nmol secreted per g liver. Thus, exposure to monoc rotaline causes disturbances in sulfur metabolism in the liver and in the composition of bile. The consequences for the digestive properties of bile and gastrointestinal toxicity remain to be established. As su lfhydryl compounds are involved in detoxification of monocrotaline met abolites, these findings indicate a mutual interaction of pyrrolizidin e toxicity and sulfur metabolism. This suggests that dietary sulfur am ino acid intake may influence susceptibility to pyrrolizidine poisonin g.