THE EFFECT OF THE PYRROLIZIDINE ALKALOIDS, MONOCROTALINE AND TRICHODESMINE, ON TISSUE PYRROLE BINDING AND GLUTATHIONE METABOLISM IN THE RAT

One day after in vivo administration of equitoxic doses of the hepatotoxic and pneumotoxic pyrrolizidine alkaloid, monocrotaline (65 mg/kg, i.p.) or the related hepatotoxic and neurotoxic alkaloid trichodesmine (15 mg/kg, i.p.) hepatic GSH levels are increased by more than 50%. These doses of alkaloids represent 60% of the LD(50) values. Accompanying these changes in GSH levels is an increase in the overall rate of GSH synthesis in supernatants of alkaloid-exposed livers. The ability of the rat to metabolize the two alkaloids was shown by the appearance of tissue-bound pyrrolic metabolites of pyrrolizidines in various organs. The levels of these metabolites appear to correlate with organ toxicity. For the hepatic and pneumotoxic alkaloid, monocrotaline, higher levels are found in liver (17 nmoles/g tissue) and lung (10 nmoles/g) than for trichodesmine (7 nmoles/g and 8 nmoles/g, respectively). For the neurotoxic alkaloid, trichodesmine, higher levels are found in brain (3.8 nmoles/g tissue) than for monocrotaline (1.7 nmoles/g tissue).