In vivo amelioration of adriamycin induced oxidative stress in plasma by gamma-glutamylcysteine ethyl ester (GCEE)

Adriamycin (ADR) is a common chemotherapeutic known to generate significant amounts of reactive oxygen species (ROS). Although ROS generation is one of several means by which ADR attacks cancerous tissues, oxidative stress-related toxicity has been documented in several non-targeted organs as a result of anthracycline chemotherapy. Oxidative damage to tissues has been shown in the past to be minimized with co-administration of various antioxidants. Gamma-glutamylcysteine ethyl ester (GCEE) is an antioxidant and precursor to glutathione that has been shown to successfully defend brain against ADR-induced oxidative stress. The current study shows ADR in vivo also causes oxidative stress in plasma in the form of protein oxidation [indexed by protein carbonyls and protein bound 3-nitrotyrosine] and lipid peroxidation [indexed by protein-bound-4-hydroxynonenal]. All three markers of oxidative stress are significantly suppressed with in vivo co-administration of GCEE. This work further supports the concept that administration of GCEE can protect patients undergoing anthracycline chemotherapy from non-targeted oxidative damage.