Evaluation of tissue indicators of oxidative stress in rats treated chronically with adriamycin.
Rats treated chronically with the anticancer agent adriamycin to a cumulative dose of 21 mg/kg, which was sufficient for development of an early stage of cardiomyopathy, were examined for evidence of lipid peroxidation and oxidative stress in vivo by several methods. Fluorometric analysis of lipid extracts suggested that fluorescent products of lipid peroxidation reactions were elevated about 3-fold in kidney, 40% in heart, and 10% in liver. However, lipid hydroperoxides and endoperoxides were not found to any significant extent in heart, liver or kidney. By contrast, as previously reported, the serum of adriamycin-treated rats showed substantial levels of lipid peroxide compounds. Measurements of glutathione levels indicated increases of about 50% in kidney and 20% in heart, and a decrease of 20% in liver, on a per gram tissue basis, after adriamycin treatment. Levels of protein-bound mixed disulfides were not altered after adriamycin treatment in heart, liver or kidney. Cardiac glutathione peroxidase activity was increased 30% after chronic adriamycin treatment, whereas glutathione reductase activity was unchanged. The results indicate that the major organs of rats treated chronically with adriamycin exhibit at least some persistent biochemical changes that are consistent with oxidative stress in vivo. The different types of lipid peroxidation products found in tissues as compared to serum may reflect, in part, the operation of membrane peroxidation repair processes.
Thayer
W S
WS
Department of Pathology and Laboratory Medicine, Hahnemann University, School of Medicine, Philadelphia, PA 19102.
D000818:Animals; D004220:Disulfides / Q000032:analysis; D004317:Doxorubicin / Q000633:toxicity*; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000032:analysis; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344
D004220:Disulfides; D005609:Free Radicals; D008054:Lipid Peroxides; D004317:Doxorubicin; D005980:Glutathione Reductase; D005978:Glutathione