Regulatory role of glutathione and soluble sulfhydryl groups in the toxicity of adriamycin.

Adriamycin (ADR) has been shown to produce free radicals in NADPH microsomal systems, to increase oxygen consumption of both hepatic microsomes and heart sarcosomes and to stimulate superoxide formation in cardiac, submitochondria particles. These reactive products could produce the cardiotoxicity of ADR by oxidizing various membrane structures, especially if the heart lacks sufficient protective reducing substances such as thiols. We examined 1) the effect of ADR on reduced glutathione (G-SH) levels in various tissues including heart, 2) the ability of the sulfhydryl (SH) donor, cysteamine, to alter soluble SH levels in heart tissue after ADR administration and 3) the effects of SH donors (cysteamine and N-acetyl cysteine and G-SH depletion by diethyl maleate on ADR-induced lethality in Swiss ICR-HA mice. A single injection of ADR (15 mg/kg i.p.) elicited a statistically significant fall in liver (P