Taurine and enzymatically modified isoquercitrin protected against methotrexate-induced deteriorations in the conductivity and rhythmicity of the heart in rats: Antioxidant, anti-inflammatory, and histological architecture approach

Cardiotoxicity is one of the most devastating complications of cancer treatment by methotrexate (MTX). The present study aimed to investigate the potential anti-cardiotoxic efficacy of taurine (Tau) and enzymatically modified isoquercitrin (EMIQ) alone or combined against MTX-induced cardiotoxicity in adult male rats. A total of 36 rats were randomly divided into six groups (six animals each): control, MTX (a single i.p. dose of 20 mg/kg), EMIQ + MTX (26 mg/kg of EMIQ, p.o. for 16 days), Tau + MTX (500 mg/kg of Tau, p.o. for 16 days), EMIQ + Tau + MTX at the same previous doses, and (EMIQ + Tau)_½ + MTX. MTX reduced the percentage of body weight change, the expression of dihydrofolate reductase (DHFR) and folypolyglutamyl synthetase (FPGS), the cleaved tumor necrosis factor alpha (TNF-α) level in the cardiac tissue, and the elevated serum TNF-α level. MTX extensively deteriorated the electrocardiography (ECG), inducing tachycardia with shortening of the time intervals between successive heartbeats (R-R interval), associated with elongation of ventricular depolarization (QRS interval), and the corrected total time for ventricular de- and repolarization (QTc) duration. Treatment with MTX resulted in a significant reduction in atrial depolarization (P amplitude) and rapid repolarization (T amplitude) and a significant elevation in plateau phase (ST height). MTX treatment resulted in swelling of cardiomyocytes with extensive vacuolization of sarcoplasm with numerous variably sized vacuoles in addition to apoptotic cells. Tau and EMIQ protected against MTX-induced deteriorations in the conductivity and rhythmicity of the heart through antioxidative, anti-inflammatory, and antiapoptotic activities. Treatment with tau and EMIQ combined at high or low doses offered superior protection to the heart than using each agent alone.