Cardioprotective effect of zofenopril, thymoquinone and their combination in cyclophosphamide-induced cardiotoxicity in rats.

Sakar Karem Abdulla, Badrul Amini Abd Rashid, Karmand Hamaamin Salih, N Mahmood, Bushra Hassan Marouf, Hemn Hassan Othman

Hum Exp Toxicol

Jan 1, 2025

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Abstract

BackgroundCyclophosphamide (Cyp) is associated with various organ toxicities. The study aimed to investigate the efficacy of zofenopril (Zf), thymoquinone (Thym), and their combination in Cyp-induced cardiotoxicity.MethodologyThirty rats were divided into five groups of six rats each. They received the following treatment orally for 19 days: Control (Con) and Cyp groups: normal saline. Zf: Zf 15 mg/kg, Thym: Thym 80 mg/kg, and Zf + Thym: a combination of both. A single dose of Cyp 200 mg/kg intraperitoneally (IP) was given on day 17 of the experiment to all the groups except the Con. Cardiac, inflammatory, and apoptotic biomarkers, including troponin T, lactate dehydrogenase (LDH), CK-MB, hs-CRP, nuclear factor kappa B (NF-κB), caspase-3, and total antioxidant capacity (TAC), along with lipid profile and histopathological lesions, were assessed.ResultsCyp resulted in cardiotoxicity as manifested by a significant increase in troponin T, CK-MB, caspase-3, hs-CRP, suppression of TAC level, and marked histopathological alterations in cardiac tissues. Zf, Thym, and their combination significantly reduced CK-MB levels. NF-κB level was significantly decreased by Thym, while the combination of Zf and Thym significantly elevated TAC. hs-CRP was significantly reduced only by Zf. Caspase-3 were significantly lowered by both Zf and Thym individually, as well as by their combination.ConclusionZf and Thym provided cardioprotection against Cyp-induced cardiotoxicity through distinct mechanisms. Zf exhibited anti-inflammatory effects, evidenced by a significant reduction in hs-CRP, along with anti-apoptotic activity. Thym significantly suppressed NF-κB expression. Their combination enhanced antioxidant capacity, however, no superiority over individual treatments was observed concerning their other actions.