Antioxidant, anti-inflammatory, and anti-apoptotic mechanisms of garlic and parsley against cardiac toxicity induced by cyclophosphamide.

Despite the availability of newer therapeutic agents, cyclophosphamide (CP) remains prescribed for certain cancers and severe autoimmune diseases; however, its use requires extreme caution because of its cardiotoxic impact. Natural antioxidants are widely used to counteract the harmful effects of chemotherapeutic drugs. In this context, garlic (GO) and parsley oils (PO) are known to possess antioxidant, anti-inflammatory, and cytoprotective properties. Therefore, the present study aimed to evaluate the protective effects of GO and PO against CP-induced cardiotoxicity, with particular emphasis on their roles in attenuating oxidative stress, inflammation, and apoptosis in cardiac tissue. Forty-nine male-Albino rats were divided into control, CP, GO, PO, GO + CP, PO + CP, and GO + PO + CP groups. Antioxidant biomarkers (SOD, CAT, GPx, and GSH), cardiac markers (LDH, CK, CK-MB, AST, cTnI), and proinflammatory cytokines (TNF-α, IL-1β, IL-6), were assessed. Apoptosis was evaluated by caspase-3 expression via qRTPCR and immunohistochemistry. Histopathological changes in the heart were examined. CP administration elevated serum oxidative stress markers, cardiac enzymes, and proinflammatory cytokines while reducing antioxidant enzyme activity. It also downregulated NrF-2 and HO-1 expression, together with Bcl2 anti-apoptotic marker expression, while it upregulated the quantitative expression of NFkB and apoptosis-associated genes. Additionally, myocardial degenerative pictures along with increased caspase-3 expression after CP administration were confirmed. GO and PO treatment restored altered antioxidant enzyme activities, suppressed inflammation, reduced apoptosis, and increased antiapoptotic genes. Significant ameliorative effects for GO and PO against CP-induced cardiotoxicity at the histopathological level were reported.