Examination of the effects of thiamine and thiamine pyrophosphate on Doxorubicin-induced experimental cardiotoxicity

J Cardiovasc Pharmacol Ther. 2015 Mar;20(2):221-9. doi: 10.1177/1074248414552901. Epub 2014 Oct 13.


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.

Keywords: cardiotoxicity; doxorubicin; thiamine; thiamine pyrophosphate; thiamine pyrophosphokinase.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Cardiotoxicity / etiology*
  • DNA Damage
  • Doxorubicin / toxicity*
  • Glutathione / analysis
  • Male
  • Malondialdehyde / analysis
  • Myocardium / pathology
  • Rats
  • Rats, Wistar
  • Thiamin Pyrophosphokinase / antagonists & inhibitors
  • Thiamin Pyrophosphokinase / genetics
  • Thiamine / pharmacology*
  • Thiamine Pyrophosphate / pharmacology*


  • Antibiotics, Antineoplastic
  • Malondialdehyde
  • Doxorubicin
  • Thiamin Pyrophosphokinase
  • Glutathione
  • Thiamine Pyrophosphate
  • Thiamine