title: The redox imbalance and the reduction of contractile protein content in rat hearts administered with L-thyroxine and Doxorubicin.
abstract: Oxidative stress and disorders in calcium balance play a crucial role in the doxorubicin-induced cardiotoxicity. Moreover, many cardiotoxic targets of doxorubicin are regulated by iodothyronine hormones. The aim of the study was to evaluate effects of tetraiodothyronine (0.2, 2 mg/L) on oxidative stress in the cardiac muscle as well as contractility and cardiomyocyte damage markers in rats receiving doxorubicin (1.5 mg/kg) once a week for ten weeks. Doxorubicin was administered alone (DOX) or together with a lower (0.2T(4) + DOX) and higher dose of tetraiodothyronine (2T(4) + DOX). Two groups received only tetraiodothyronine (0.2T(4), 2T(4)). Coadministration of tetraiodothyronine and doxorubicin increased the level of lipid peroxidation products and reduced RyR2 level when compared to untreated control and group exposed exclusively to doxorubicin. Insignificant differences in SERCA2 and occasional histological changes were observed. In conclusion, an increase of tetraiodothyronine level may be an additional risk factor of redox imbalance and RyR2 reduction in anthracycline cardiotoxicity.
authors.affiliation: Medical Biology Unit, Medical University of Lublin, Lublin, Poland. a.korg@interia.pl
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Korga
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Dudka
authors.forename: Franciszek
authors.initials: F
authors.lastname: Burdan
authors.forename: Justyna
authors.initials: J
authors.lastname: Sliwinska
authors.forename: Slawomir
authors.initials: S
authors.lastname: Mandziuk
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Dawidek-Pietryka
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D003285:Contractile Proteins / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013974:Thyroxine / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D003285:Contractile Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D004317:Doxorubicin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013974:Thyroxine