Evaluation of the protective effects of Syzygium aromaticum L. against doxorubicin-induced cardiotoxicity in rats

OBJECTIVE Doxorubicin (DOX), a widely used anthracycline chemotherapy drug, has the potential to cause toxicity in multiple organs, particularly the myocardium. This study examines the cardioprotective effects of Syzygium aromaticum L. extract (SAE) in DOX-induced cardiotoxicity. METHODS This study involved 48 male Wistar rats (250-300 g), divided into (n = 8): Sham, Doxorubicin (DOX 2 mg/kg intraperitoneally every 48 h for 12 days), SAE groups (DOX plus SAE orally, 50, 100, and 200 mg/kg/day), and Vitamin E (DOX plus Vitamin E orally at 100 mg/kg/day) over a 20-day period, beginning four days before DOX administration. RESULTS We revealed that DOX significantly lowered body weight, heart tissue weight, reduced glutathione (GSH), and interleukin (IL)-10 levels, while increasing lactate dehydrogenase (LDH), troponin, creatine kinase (CK-MB), malondialdehyde (MDA), TNF-α, IL-6, and TGF-β, as well as histopathological damage in heart tissue (q < 0.001). In contrast, treatment with all three doses of SAE and Vitamin E significantly reduced oxidative, inflammatory, and fibrotic markers, as well as histopathological injury, after DOX-induced cardiotoxicity (q < 0.05 to <0.001). In addition, DOX significantly increased left ventricular (LV) end-systolic diameter (LVESD) and LV end-diastolic diameter (LVEDD), while LV ejection fraction (LVEF) and LV fractional shortening (LVFS) were decreased considerably compared to the sham group (q < 0.001). In contrast, treatment involving SAE and vitamin E markedly decreased these echocardiographic markers (q < 0.05 to <0.001) compared to the DOX group. CONCLUSION SAE extract markedly ameliorated cardiotoxicity caused by doxorubicin by demonstrating antioxidant, anti-inflammatory, and anti-fibrotic properties. Nonetheless, additional mechanistic studies, pharmacokinetic investigations, safety assessments, and clinical research is necessary to verify its efficacy.