Electrophysiological, biochemical, and histopathological evidence of thymoquinone-mediated protection in cisplatin-induced cardiotoxicity

Cisplatin (CIS)-induced cardiotoxicity is an important but underrecognized adverse effect that may limit the clinical use of this widely employed chemotherapeutic agent. Oxidative stress (OS) plays a central role in CIS-related cardiac injury. This study aimed to investigate the potential protective effects of thymoquinone (TQ) against acute CIS-induced cardiotoxicity in rats. Thirty-two male Wistar albino rats were simple randomly divided into four groups: Control, CIS, TQ, and CIS + TQ. Acute cardiotoxicity was induced using a single i.p. dose of CIS (7 mg/kg), while TQ was administered i.p. at 5 mg/kg/day for 3 days; therefore, this protocol did not model chronic or cumulative CIS exposure. Hemodynamic parameters and electrocardiographic recordings were obtained to assess cardiac conduction and rhythm. Serum creatine kinase, troponin, and lactate dehydrogenase levels were measured as markers of myocardial injury. OS parameters in heart tissue were evaluated, and histopathological examination was performed. CIS administration induced significant cardiac injury, evidenced by increased arrhythmia incidence, alterations in QRS duration, elevated serum cardiac biomarkers, enhanced myocardial lipid peroxidation, depletion of antioxidant defenses, and marked histopathological damage. TQ co-administration significantly reduced serum cardiac injury markers, restored myocardial antioxidant status, and ameliorated histopathological alterations, while effects on electrophysiological abnormalities showed only a non-significant descriptive trend. TQ alone did not produce adverse cardiac effects. TQ attenuated biochemical, OS, and histopathological indicators of acute CIS-induced cardiac injury in rats. However, these preclinical findings do not establish therapeutic efficacy, and studies using chronic CIS treatment protocols, tumor-bearing animals, and clinical investigations are required before the potential adjunctive use of TQ can be considered.