Investigation of the cardioprotective effects of thymoquinone in doxorubicin induced heart failure

Objective: In this study, we examined the effect of thymoquinone (TQ) on cardiac changes induced by administration of doxorubicin (DOX). Therefore, electrophysiological properties and cellular mechanisms likely to affect these parameters were investigated in cardiomyocytes isolated from rat hearts. Method: Heart failure model was performed by administering DOX. During 4-week experiment, DOX (3 mg/kg/each) was injected subcutaneously into DOX and DOX+TQ groups in 5 times. TQ (10 mg/kg) was administered to DOX+TQ and CON+TQ groups by gavage. At the end of 4 weeks, fractional shortening, action potential (AP), L-type Ca+2, and K+ channel currents were recorded from isolated ventricular myocytes. Protein expression levels were measured by the Western blotting method. Protein carbonyl and total antioxidant capacity (TAC) were measured by kits. Results: While an increase in sarcomere length and a decrease in fractional shortening was measured in the DOX group myocytes, the relaxation time was prolonged. TQ application improved these parameters significantly. There was a prolongation in AP repolarization time of DOX and DOX+TQ group myocytes, although in DOX group, the prolongation was not significant. While Ca+2 channel currents increased in DOX group, TQ application restored these changes and altered Ca+2 channel kinetics. While there was no change in K+ current amplitudes, channel kinetics were slower in the DOX group myocytes. When protein expressions were examined, p-PLN/PLN expression increased in DOX and DOX+TQ groups, while SERCA, CAMKII, p-CAMKII and procaspase-3 protein expression levels were decreased. There was no difference in NOX protein expression, TAC, and protein carbonyl levels between groups. Conclusion: As a result, it was observed that TQ could not completely prevent the electrophysiological abnormalities associated with DOX-induced heart failure. Also, it was observed that DOX did not increase the amount of ROS and TQ did not alter the antioxidant level.