title: Intensification of doxorubicin-related oxidative stress in the heart by hypothyroidism is not related to the expression of cytochrome P450 NADPH-reductase and inducible nitric oxide synthase, as well as activity of xanthine oxidase.
abstract: Cytochrome P450 NADPH-reductase (P450R), inducible synthase (iNOS) and xanthine oxidase play an important role in the antracycline-related cardiotoxicity. The expression of P450R and iNOS is regulated by triiodothyronine. The aim of this study was to evaluate the effect of methimazole-induced hypothyreosis on oxidative stress secondary to doxorubicin administration. 48 hours after methimazole giving cessation, rats were exposed to doxorubicin (2.0, 5.0 and 15 mg/kg). Blood and heart were collected 4, 48 and 96 h after the drug administration. Animals exposed exclusively to doxorubicin or untreated ones were also assessed. The hypothyreosis (0.025% of methimazole) significantly increased the doxorubicin effect on the cardiac carbonyl group and they may increase the glutathione level. An insignificant effect of methimazole was noticed in case of the cardiac lipid peroxidation product, the amount of DNA oxidative damages, iNOS and xanthine oxidase-enzymes responsible for red-ox activation of doxorubicin. However, the concentration of P450R was affected by a lower dose of methimazole in rats administered with doxorubicin. Since in rats receiving doxorubicin changes in oxidative stress caused by methimazole were not accompanied by elevation of bioreductive enzymes, it may be concluded that these changes in the oxidative stress were not related to the tested enzymes.
authors.affiliation: Medical Biology Unit, Medical University of Lublin, 20-059 Lublin, Poland. ave123@wp.pl
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Dudka
authors.forename: Franciszek
authors.initials: F
authors.lastname: Burdan
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Korga
authors.forename: Magdalena
authors.initials: M
authors.lastname: Iwan
authors.forename: Barbara
authors.initials: B
authors.lastname: Madej-Czerwonka
authors.forename: Monika
authors.initials: M
authors.lastname: Cendrowska-Pinkosz
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Korobowicz-Markiewicz
authors.forename: Barbara
authors.initials: B
authors.lastname: Jodlowska-Jedrych
authors.forename: Wlodzimierz
authors.initials: W
authors.lastname: Matysiak
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D013956:Antithyroid Agents / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D006321:Heart / Q000187:drug effects; D007037:Hypothyroidism / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000097:blood; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D013956:Antithyroid Agents; D014284:Triiodothyronine; D008713:Methimazole; D004317:Doxorubicin; D052247:Nitric Oxide Synthase Type II; D014969:Xanthine Oxidase; D009251:NADPH-Ferrihemoprotein Reductase