Abstract
Up until now, the specific mechanisms involved in doxorubicin (DOX)-induced cardiotoxicity have not been fully elucidated. Since thiamine deficiency is associated with myocardial dysfunction and it may lead to cardiomyopathy, we aimed to investigate whether thiamine (Vitamin B1) treatment provides cardioprotection and modulates DOX mediated subchronic cardiotoxicity as well as to determine possible mechanisms of its effects. The study involved 48 Wistar albino rats divided into four groups: healthy non-treated rats and healthy rats treated with thiamine and DOX rats without treatment and DOX rats treated with thiamine. DOX was applied as a single i.p.injection (15mg/kg), while thiamine treatment lasted 7days (25mg/kg/dayi.p.). Before and after the treatment hemodynamic changes were monitored in vivo by echocardiography. When the protocol was completed, animals were sacrificed and rat hearts were isolated in order to evaluate parameters of cardiac oxidative stress [superoxide anion radical-O2−, hydrogen peroxide-H2O2, nitric oxide-NO−, index of lipid peroxidation-thiobarbituric acid (TBA) reactive substances (TBARS), superoxide dismutase – SOD, catalase (CAT), and reduced glutathione-GSH] and apoptosis (Bax, Bcl-2, caspases). DOX treatment significantly reduced the ejection fraction, while thiamine treatment led to its minor increase in the DOX-treated group. In that sense, heart oxidative stress markers were significantly increased in DOX-treated rats, while therapeutic dose of thiamine decreased the levels of free radicals. Our study demonstrated the promising ameliorative effects of thiamine against DOX-induced cardiotoxicity through modulation of oxidative stress, suppression of apoptosis, and possibility to improve myocardial performance and morphometric structure of rats` hearts.
Highlights
Thiamine is an essential water-soluble vitamin playing an important role in the cellular metabolism of human body (Eshak and Arafa, 2018)
Thiamine treatment led to a slight increase in the DOX-treated group compared to alone DOX administration, whereas there were no statistically significant ejection fraction changes in CTRL group during observed experimental period (Table 1)
After DOX single injection, value of O2− in heart tissue was significantly higher (89%) in DOX group compared to that in CTRL, while its co-administration with thiamine led to the reduction in the level of this marker (19.4%)
Summary
Thiamine (vitamin B1 or aneurin) is an essential water-soluble vitamin playing an important role in the cellular metabolism of human body (Eshak and Arafa, 2018) It exists in three different forms depending on its phosphorylation status, including thiamine monophosphate, thiamine diphosphate, and thiamine triphosphate. In the Krebs cycle, TPP is required for adequate PDH complex functioning which converts pyruvate to acetyl CoA, as well as for a-KGDH which possesses the ability to convert alpha-ketoglutarate to succinate. Both of these two reactions are indispensable steps for aerobic metabolism and ATP production. As a cofactor of TKT enzyme, TPP is important for the pentose phosphate pathway, maintaining cell redox through higher formation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH; Zastre et al, 2013; Manzetti et al, 2014; Kattoor et al, 2018)
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