Effects of pyrrolidine dithiocarbamate on antioxidant enzymes in cardiomyopathy induced by adriamycin in rats.

OBJECTIVE: The clinical usefulness of adriamycin (ADR) is restricted by the frequent induction of dose-dependent chronic cardiomyopathy. Previous studies on ADR cardiotoxicity have reported that the formation of free reactive oxygen radicals might be involved in ADR cardiotoxicity. Pyrrolidine dithiocarbamate (PDTC) is a potent antioxidant in vivo and in vitro. The present study was undertaken to examine the effects of PDTC on antioxidant enzymes in cardiomyopathy induced by ADR in rats.

METHODS: Thirty-two male Wistar rats were randomly divided into 4 groups: control, ADR, PDTC, and ADR+PDTC. After 30 days, myocardial histopathological and electron microscopic examinations were performed: the myocardial content of superoxide anion and lipid peroxides were examined; the myocardial total antioxygenation capability (T-AOC) and activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were examined; myocardial GSH-Px, Mn-SOD and Cu,Zn-SOD gene expressions were examined by RT-PCR analysis, and the myocardial expression of GSH-Px, Mn-SOD and Cu,Zn-SOD proteins was assessed by Western blot analysis.

RESULTS: At 30 days, ADR-induced cardiomyopathy was confirmed by structural examination. The changes were prevented by PDTC. Myocardial superoxide anion and lipid peroxides were increased by ADR, and these changes were also inhibited by PDTC. ADR decreased myocardial T-AOC and the activity of GSH-Px and SOD, and these changes were likewise inhibited by PDTC. mRNA and protein expression of GSH-Px and Mn-SOD were depressed by ADR treatment and prevented by PDTC. Cu,Zn-SOD mRNA and protein levels were not significantly changed by ADR or PDTC.

CONCLUSION: PDTC prevented ADR cardiomyopathy in rats by upregulating GSH-Px and SOD activation, which is associated with changes in the expression of GSH-Px and Mn-SOD transcript and protein levels.