Biomaterial Database

Examination of the effects of thiamine and thiamine pyrophosphate on Doxorubicin-induced experimental cardiotoxicity. 2015

B Polat, and Halis Suleyman, and E Sener, and F Akcay

Department of Pharmacology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008315	Malondialdehyde	The dialdehyde of malonic acid.	Malonaldehyde,Propanedial,Malonylaldehyde,Malonyldialdehyde,Sodium Malondialdehyde,Malondialdehyde, Sodium
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004317	Doxorubicin	Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.	Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000903	Antibiotics, Antineoplastic	Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.	Antineoplastic Antibiotics,Cytotoxic Antibiotics,Antibiotics, Cytotoxic
D013831	Thiamine	3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2- hydroxyethyl)-4-methylthiazolium chloride.	Aneurin,Vitamin B 1,Thiamin,Thiamine Mononitrate,Vitamin B1,Mononitrate, Thiamine
D013835	Thiamine Pyrophosphate	The coenzyme form of Vitamin B1 present in many animal tissues. It is a required intermediate in the PYRUVATE DEHYDROGENASE COMPLEX and the KETOGLUTARATE DEHYDROGENASE COMPLEX.	Cocarboxylase,Thiamine Diphosphate,Berolase,Pyrophosphate, Thiamine