Cardioprotective effect of Cymbopogon proximus and febuxostat on venlafaxine induced subacute cardiotoxicity in adult male Albino rats: Histological and immunohistochemical study.

Cardiotoxicity linked to the commonly prescribed antidepressant venlafaxine represents a major worldwide clinical challenge and patient safety concern. There is a pressing need for efficient interventions because there are currently no recognized protective agents that specifically target venlafaxine-induced cardiac damage. Cymbopogon proximus is a natural plant whose extract contains antioxidants and anti-inflammatory properties. Febuxostat, a xanthine oxidase inhibitor, exhibits anti-inflammatory, antioxidant, and immune-modulating impact beyond its primary use, suggesting potential for repurposing. This investigation critically evaluates the efficiency of C. proximus extract and febuxostat in protection against venlafaxine-induced subacute cardiac damage to address this critical gap. 72 rats in 6 groups: I (control); II (C. proximus 800 mg/kg, daily oral gavage); III (febuxostat 10 mg/kg, daily oral gavage); IV (venlafaxine 50 mg/kg via oral gavage every 10 days for 30 days); V (venlafaxine + C. proximus); VI (venlafaxine + febuxostat). After 30 days of treatment, the rats were euthanized for testing. The groups treated with C. proximus extract or febuxostat exhibited much higher survival rates among rats that were affected by venlafaxine toxicity. These treatments effectively restored cardiac indices to near-normal levels and attenuated pathological alterations, evidenced by reduced nuclear positivity of PCNA staining, significant decreases in pro-inflammatory markers, increased redox indicators, and downregulation of key mediators: fibrosis driver TGF-β, cardiac stress marker BNP, along with Collagen-α1 and MMP2. Furthermore, levels of ALT, AST, creatinine, and BUN were maintained within normal ranges in the treated groups. These data demonstrate that C. proximus extract and febuxostat confer significant cardioprotective effects against venlafaxine-induced subacute cardiac toxicity, primarily mediated via their antioxidant and anti-inflammatory properties.