MODULATION OF KETAMINE-INDUCED MYOCARDIAL INFLAMMATION BY METHANOLIC EXTRACT AND BIOACTIVE FRACTIONS OF DACRYODES EDULIS IN WISTAR RATS: AN IMMUNOHISTOCHEMICAL EVALUATION OF TNF-Α AND IL-6 EXPRESSION

Objective: Ketamine, a widely used anesthetic and recreational agent, is increasingly associated with dose-dependent cardiotoxicity, including inflammation and myocardial injury. This study evaluated the cardioprotective effects of Dacryodes edulis methanolic extract and its bioactive fractions (flavonoid, saponin, alkaloid) against ketamine-induced myocardial inflammation in adult Wistar rats, focusing on the immunohistochemical expression of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Methods: Forty-eight adult male Wistar rats (≈0.2 kg) were divided into eight groups. Myocardial inflammation was induced through intraperitoneal administration of ketamine at 100, 150, and 200 mg/kg/day for 21 days. Treatment groups received oral administration of “D. edulis” methanolic extract (142 mg/kg/day), saponin fraction (142 mg/kg/day), alkaloid fraction (192 mg/kg/day), or flavonoid fraction (164 mg/kg/day) for 21 consecutive days. Hearts were harvested for histological and immunohistochemical analysis, and IL-6 and TNF-α expressions were assessed semiquantitatively. Results: Ketamine caused dose-dependent upregulation of IL-6 and TNF-α, with the highest expression observed at 200 mg/kg. Administration of the methanolic extract moderately reduced cytokine expression. The saponin fraction completely suppressed IL-6 and TNF-α, whereas the flavonoid fraction significantly attenuated expression, showing mild positivity. The alkaloid fraction failed to reduce cytokine levels and displayed marked expression similar to high-dose ketamine. Conclusion: Ketamine induces dose-dependent myocardial inflammation through upregulation of IL-6 and TNF-α. The flavonoid and saponin fractions of D. edulis exert potent immunomodulatory and cardioprotective effects, with flavonoids showing the most consistent attenuation. These findings highlight the therapeutic potential of D. edulis phytochemicals in mitigating drug-induced cardiotoxicity and provide a basis for future studies exploring plant-based cardioprotective interventions.