Examination of the Effects of Thiamine and Thiamine Pyrophosphate on Doxorubicin-Induced Experimental Cardiotoxicity

作者：Polat B; Suleyman Halis^*; Sener E; Akcay F

来源：Journal of Cardiovascular Pharmacology and Therapeutics, 2015, 20(2): 221-229.

DOI：10.1177/1074248414552901

• cardiotoxicity
• doxorubicin
• thiamine
• thiamine pyrophosphate
• thiamine pyrophosphokinase

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.

• 出版日期2015-3