Effects of Adriamycin on Cardiac Ultrastructure and Glutathione-Glutathione Peroxidase System in Mouse

Adriamycin이 생쥐 심근 미세구조 및 Glutathione-Glutathione Peroxidase계에 미치는 영향

The cardiotoxic effects of acute and chronic administration of adriamycin (ADR) were evaluated in A/J Swiss albino mice. In acute studies, male mice received intravenous ADR, 5mg or 15mg/kg per day for 3 or 1day and were sacrifice 12 hours later. Because the glutathione-glutathione peroxidase system is major pathway for free radical detoxication, glutathione levels and glutathione peroxidase activity was measured. In acute studies, ADR-treated mice exhibited significantly decreased levels(p<0.05) of total glutathione and unchanged levels of oxidized glutathione and percentage of oxidized glutathione. The earliest myocardial fine structural alterations included swelling and degeneration of mitochondria and dilatation of sarcoplasmic reticulum at all dosage of acute models. In chronic studies, mice received 5mg/kg ADR once a week for up to 16 weeks. Levels of total and reduced glutathione were decreased significantly(p<0.01) and oxidized glutathione and percentage of oxidized glutathione were increased significantly (p<0.05). Chronic myocardial lesions included perinuclear vacuolization, seperation of myofibrils and the fasciae adherens of intercalated disc and hypercontraction band within myocyte. Glutathione peroxidase activity reduced significantly (p<0.01) in any group of acute and chronic ADR-treated animals. Test for lipid peroxidation(malondialdehyde) was increased significantly(P<0.01). Thus, we conclude 1) ADR significantly lowers glutathione levels in heart tissue, and 2) cellular damage progress produced by alteration of this system in mouse models of ADR cardiotoxicity. These results suggest that the glutathione-glutathione peroxidase system may be involved in the modulation of ADR-induced cardiotoxicity.