PZ-51 (Ebselen) in vivo protection against adriamycin-induced mouse cardiac and hepatic lipid peroxidation and toxicity.
Adriamycin (Adr)-induced cardiotoxicity occurs most likely via an oxidative mechanism of action. Moderation of this activity may result in an improved therapeutic index for this compound. PZ-51, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one, is a selenoorganic compound with thiol-dependent, peroxidase-like activity. We tested this compound alone and in combination with N-acetylcysteine (NAC) for its effect on Adr-induced in vivo toxicity in Balb/c mice. These studies demonstrated that PZ-51 protects against Adr-induced lipid peroxidation in heart and liver tissue and Adr-induced toxicity in general, as measured by total serum creatine kinase activity and body weight.
Pritsos
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Department of Nutrition and Cellular and Molecular Pharmacology, University of Nevada, Reno 89557.
Sokoloff
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Gustafson
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D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D003402:Creatine Kinase / Q000097:blood; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004347:Drug Interactions; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced* / Q000517:prevention & control; D054833:Isoindoles; D015227:Lipid Peroxidation / Q000187:drug effects*; D008107:Liver Diseases / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D016566:Organoselenium Compounds / Q000494:pharmacology*
D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D004317:Doxorubicin; D003402:Creatine Kinase; D000111:Acetylcysteine