title: Examination of the effects of thiamine and thiamine pyrophosphate on Doxorubicin-induced experimental cardiotoxicity.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  The cardiotoxic effect of doxorubicin originated from the inhibition of TPK enzyme resulting in insufficient production of thiamine pyrophosphate.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Polat
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey halis.suleyman@gmail.com.
authors.forename: Halis
authors.initials: H
authors.lastname: Suleyman
authors.affiliation: Department of Pathology, Erzurum Regional Education and Research Hospital, Erzurum, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Sener
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Akcay
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D066126:Cardiotoxicity / Q000209:etiology*; D004249:DNA Damage; D004317:Doxorubicin / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013836:Thiamin Pyrophosphokinase / Q000037:antagonists & inhibitors / Q000235:genetics; D013831:Thiamine / Q000494:pharmacology*; D013835:Thiamine Pyrophosphate / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D008315:Malondialdehyde; D004317:Doxorubicin; D013836:Thiamin Pyrophosphokinase; D005978:Glutathione; D013835:Thiamine Pyrophosphate; D013831:Thiamine
keywords: cardiotoxicity; doxorubicin; thiamine; thiamine pyrophosphate; thiamine pyrophosphokinase