Oxidative damage in selenium deficient hearts on perfusion with adriamycin: protective role of glutathione peroxidase system

Abstract

The protective effects of the glutathione peroxidase system against functional damage induced by perfusion of isolated hearts with adriamycin, an anthracycline antibiotic, were studied. We used selenium deficient rats, in which cardiac glutathione peroxidase activity was only 3% of control rats. Both contractile tension and coronary flow decreased during perfusion with the antibiotic. The degree of decline was significantly greater in the selenium deficient hearts than in the control hearts. The increase in malondialdehyde, a product of lipid peroxidation, induced by adriamycin perfusion was more evident in selenium deficient hearts, though the level of reduced glutathione was well maintained. Isolated mitochondrial function also decreased after aerobic adriamycin perfusion and the decrease was greater in selenium deficient rats. These observations indirectly suggest that the decrease in cardiac function induced by adriamycin is protected by the glutathione peroxidase system and that the decrease may be due, at least in part, to damage to the mitochondria caused by oxygen radicals generated by adriamycin.

Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox‐methylation balance

“…In our study selenium deficiency resulted in increased oxidant stress, a reduction in GPx‐1 expression and activity, and a reduction in systolic function similar to findings observed in prior reports . While the effect on myocardial contractility could be secondary to previously reported abnormalities in calcium handling and contractile machinery , the effects of selenium depletion on myocardial fibrosis have not been well studied.…”

Influence of Alternative Tubulin Inhibitors on the Potency of Epirubicin-Immunochemotherapeutic Synthesized with an Ultra Violet Light-Activated Intermediate

“…Presumably the highest levels of additive and synergistic cytotoxic anti-neoplastic potency and widest margin-of-safety can be attained when benzimidazole anthelmintics or griseofulvin are substituted for conventional tubulin/microtubule inhibitor chemotherapeutics in combination regimens that also apply covalent anthracyline-immunochemotherapeutics with properties of selective “targeted” delivery. Such considerations are critically important to the development of safer and more effective treatment regimens in order to reduce collateral cardiotoxicity (Danesi et al, 2006; Last et al, 2003; Nakano, Takeshige, Toshima, Tokunaga, & Minakami 1989) and nephroticity (Bulucu et al, 2008) that commonly limit systemic anthracycline administration.…”

“…Cardiotoxicity (doxorubicin ≫ epirubicin) (Danesi et al, 2006; Last et al, 2003; Nakano et al, 1989), nephroticity (Bulucu et al, 2008) and chemotherapeutic resistance represent complications that can commonly limit anthracycline administration in modern clinical oncology. The molecular design and methodology delineated for the synthetic production of covalent epirubicin-immunochemotherapeutics utilizing a UV-photoactivated anthracycline intermediate addresses a need to discover and optimize laboratory methods for the expedient production of anti-cancer therapies at higher end-product yields that possess properties of selective “targeted” delivery that complement the efficacy and potency of conventional and unconventional chemotherapeutics.…”

Selenistasis: Epistatic Effects of Selenium on Cardiovascular Phenotype

“…Selenium deficiency worsens, and selenium supplementation abrogates, myocardial injury [49,50,51,52]. In doxorubicin-induced cardiomyopathy, in which oxidant stress plays a major role, selenium deficiency has been shown to worsen cardiac pathology, with the opposite effect observed with selenium supplementation [53,54,55,56,57]. In some studies, however, a beneficial effect of selenium supplementation was not observed [58,59].…”