Examination of the Effects of Thiamine and Thiamine Pyrophosphate on Doxorubicin-Induced Experimental Cardiotoxicity. (March 2015)

• Record Type: Journal Article
• Authors: Polat, B.; Suleyman, Halis; Sener, E.; Akcay, F.
• Is Part Of: Journal of cardiovascular pharmacology and therapeutics. Volume 20:Number 2(2015:Mar.)
• Page Start: 221
• Page End: 229
• Publication Date: 2015-03
• Subjects: cardiotoxicity -- doxorubicin -- thiamine -- thiamine pyrophosphate -- thiamine pyrophosphokinase; Cardiovascular pharmacology -- Periodicals; Cardiovascular system -- Diseases -- Treatment -- Periodicals; 616
• DOI: 10.1177/1074248414552901
• Languages: English
• ISSNs: 1074-2484

Abstract

Background and Purpose: To investigate the effect of thiamine and thiamine pyrophosphate on doxorubicin-induced cardiotoxicity biochemically and histopathologically and to examine whether doxorubicin cardiotoxicity is related to the conversion of thiamine into thiamine pyrophosphate and inhibition of thiamine pyrophosphokinase (TPK) enzyme. Experimental Approach: A total of 48 Albino Wistar male rats were used. Rats were divided into groups as thiamine + doxorubicin (TIA + DOX), thiamine pyrophosphate + doxorubicin (TPP + DOX), DOX, and healthy (HEA) groups. One hour after the administration of thiamine and TPP in 25 mg/kg doses, 5 mg/kg doxorubicin were injected to all groups except HEA group during 7 days. Then, the samples were collected for biochemical (glutathione [GSH], malondialdehyde [MDA], DNA damage, creatine kinase (CK), CK-MB, and troponine I [TP-I]), molecular (TPK), and histopathological examinations. Key Results: Oxidant parameters (MDA and DNA damage) decreased and antioxidant parameter (GSH) increased in TPP + DOX group. In addition, levels of CK, CK-MB, and TP-I were low in the TPP + DOX group and high in the TIA + DOX and DOX groups. Cardiac tissue was protected in TPP + DOX group, and no protective effect was observed in TIA + DOX and DOX groups. Messenger RNA expression of TPK was decreased in DOX and TIA + DOX groups. Conclusion and Implications: The cardiotoxic effect of doxorubicin originated from the inhibition of TPK enzyme resulting in insufficient production of thiamine pyrophosphate.