Cardiac glutathione: Diurnal rhythm and variation in drug-induced cardiomyopathy

Reduced glutathione (GSH) levels in the rat heart and liver following administration of two known cardiac toxins were examined. Isoproterenol (100 mg/kg) caused cardiac GSH to rapidly decrease to 60% of control levels and to remain low at all times examined up to 24 hr. Following Adriamycin (ADR) administration, cardiac and hepatic GSH showed very variable dose-dependent alterations. At the lowest dose studied (15 mg/kg) cardiac GSH showed a small increase at 24 hr; hepatic GSH was also elevated at 6 and 24 hr. A large dose of ADR (30 mg/kg) caused no cardiac GSH alteration, but hepatic GSH levels rose to 60% above controls by 24 hrs. A massive dose of ADR caused a moderate decrease in cardiac GSH which was evident at 6 hr; hepatic GSH abruptly fell at 1 and 6 hr and subsequently rose to above control level by 24 hr. These findings indicate that although GSH is involved in the acute toxic mechanism of ADR cellular injury, rat myocardium is evidently quite resistant to this GSH-related mechanism. In addition, a distinct diurnal variation in cardiac GSH was demonstrated with the zenith near midnight and the nadir approximately at noon. Diurnal variation in the severity of isoproterenol cardiotoxicity was also examined, and found to be lacking.