Search

Unfortunately, in patients with cancer disease, clinical application of antineoplastic drug results in severe side effects of cardiotoxicity. We aim to review the research focused on elimination or reduction of antineoplastic drug-induced cardiotoxicity without affecting its anticancer efficacy by different agens. This study is based on pertinent papers that were retrieved by a selective search using relevant keywords in PubMed and ScienceDirect. Based on mentioned purpose, various strategies were investigated and proposed, and thousands of compounds were screened. The literature mainly focusing on drugs, natural products and herb extracts with therapeutic efficacies as well as non-pharmacological treatment against differently induced cardiotoxicity during treatment in patients with cancers. Larger future studies are necessary to reach a point of secure cytostatic therapy, improved patient survival and quality of life. Until that moment, baseline and serial cardiac evaluation is recommended to facilitate early identification and treatment of cardiotoxicity.

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.

Previous studies have suggested that thiamine has antioxidant activity and could decrease the production of ROS in various disorders. Our study focused on the effect of thiamine hydrochloride in the reversal of DOX-induced cardiotoxicity and compared it with the reversal in the absence of thiamine pre-treatment. Rats were divided into groups as follows: (a) thiamine + doxorubicin (TIA + DOX), (b) doxorubicin (DOX) and c) healthy (CTRL) groups. For 7 days, thiamine hydrochloride was administered at a dose of 25 mg/kg per day intraperitoneally, while a single dose of 15 mg/kg doxorubicin was injected into all groups except the CTRL group. We measured the following parameters: maximum rate of left ventricular development (dp/dt max), minimum rate of left ventricular development (dp/dt min), systolic left ventricular development (SLVP), diastolic left ventricular development (DLVP), heart rate (HR) and coronary flow (CF), pro-oxidative and antioxidative markers, cardiac activity, and histopathological evaluation. In our study, cardiac contractility was significantly altered after DOX treatment and diminished by thiamine pre-treatment. Additionally, pro-oxidant parameters were significantly increased in the DOX group. The levels of O2−, H2O2 and TBARS were significantly increased in the DOX group and decreased in the DOX + T group compared to those in the DOX group. Morphometric analyses showed moderately expressed interstitial fibrosis and degenerately modified cardiac muscle fibres, with signs of interfibrillary congestion, vacuolar degeneration and myocytolysis in the DOX group as visualized by H&E and Masson’s Trichrome staining. Pre-treatment of thiamine hydrochloride before doxorubicin administration could decrease oxidative stress production, increase myocardial contractility and enhance the antioxidant defence system.