The Effects of Thiamine Hydrochloride on Cardiac Function, Redox Status and Morphometric Alterations in Doxorubicin-Treated Rats

摘要

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 O-2(-), 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.