The Effects of Thiamine Hydrochloride on Cardiac Function, Redox Status and Morphometric Alterations in Doxorubicin-Treated Rats.
Tanja RadonjicMarina RankovicMarko RavicVladimir ZivkovicIvan SrejovicJovana JeremicNevena JeremicJasmina SretenovicStevan MaticVladimir JakovljevicTamara Nikolic TurnicPublished in: Cardiovascular toxicology (2020)
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.
Keyphrases
- left ventricular
- heart failure
- oxidative stress
- hypertrophic cardiomyopathy
- heart rate
- acute myocardial infarction
- blood pressure
- aortic stenosis
- drug delivery
- mitral valve
- cardiac resynchronization therapy
- left atrial
- anti inflammatory
- cancer therapy
- cystic fibrosis
- dna damage
- ischemia reperfusion injury
- skeletal muscle
- cell death
- aortic valve
- signaling pathway
- reactive oxygen species
- endoplasmic reticulum stress
- induced apoptosis
- transcatheter aortic valve replacement
- flow cytometry