Tirapazamine-doxorubicin interaction referring to heart oxidative stress and Ca²⁺ balance protein levels.
Doxorubicin (DOX) causes long-term cardiomyopathy that is dependent on oxidative stress and contractility disorders. Tirapazamine (TP), an experimental adjuvant drug, passes the same red-ox transformation as DOX. The aim of the study was to evaluate an effect of tirapazamine on oxidative stress, contractile protein level, and cardiomyocyte necrosis in rats administered doxorubicin. Rats were intraperitoneally injected six times once a week with tirapazamine in two doses, 5 (5TP) and 10 mg/kg (10TP), while doxorubicin was administered in dose 1.8 mg/kg (DOX). Subsequent two groups received both drugs simultaneously (5TP+DOX and 10TP+DOX). Tirapazamine reduced heart lipid peroxidation and normalised RyR2 protein level altered by doxorubicin. There were no significant changes in GSH/GSSG ratio, total glutathione, cTnI, AST, and SERCA2 level between DOX and TP+DOX groups. Cardiomyocyte necrosis was observed in groups 10TP and 10TP+DOX.
Department of Clinical Pathomorphology, Medical University in Lublin, Lublin, Poland.
Justyna
J
Sliwinska
Jaroslaw
J
Dudka
Agnieszka
A
Korga
Franciszek
F
Burdan
Wlodzimierz
W
Matysiak
Barbara
B
Jodlowska-Jedrych
Slawomir
S
Mandziuk
Katarzyna
K
Dawidek-Pietryka
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D004802:Eosinophilia / Q000097:blood / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D000077704:Tirapazamine; D014227:Triazines / Q000494:pharmacology*; D019210:Troponin I / Q000097:blood
D015415:Biomarkers; D011506:Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D014227:Triazines; D019210:Troponin I; D000077704:Tirapazamine; D004317:Doxorubicin; D004247:DNA; D001219:Aspartate Aminotransferases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium