Determination Of LD₅₀ Of Naja ashei Venom And Its Effects On The Heart And Serum Electrolytes In BALB/c Mice Through Intraperitoneal, Subcutaneous And Intramuscular Routes

Introduction: Naja ashei envenomation causes severe local and systemic toxicity, yet experimental evidence on route-dependent lethality, electrolyte disturbances, and cardiotoxicity remains limited. This study determined the median lethal dose (LD₅₀) of Naja ashei venom in BALB/c mice after intraperitoneal, intramuscular, and subcutaneous administration and evaluated electrolyte imbalance and cardiac injury.

Materials and Methods: Fresh Naja ashei venom was collected, lyophilized, and characterized. One hundred BALB/c mice received venom doses through intraperitoneal, intramuscular, or subcutaneous routes. LD₅₀ values were calculated using the Reed-Muench method and confirmed by probit and dose-response analyses. Cardiac injury was assessed using creatine kinase-MB and troponin assays, while histopathological examination of cardiac tissue confirmed venom-induced myocardial damage.

Results: Venom profiling showed predominance of three-finger toxins (~69%) and phospholipase A2 (~27%), consistent with cytotoxic and systemic activity. Toxicity was route dependent, with intraperitoneal administration producing the lowest LD₅₀ (0.70 mg/kg), followed by intramuscular (2.36 mg/kg) and subcutaneous (2.69 mg/kg) routes. Envenomation caused severe hyperkalemia (mean 7.8 mmol/L) with hyponatremia. Mean troponin-I reached 11.7 ± 5.6 ng mL⁻¹, while creatine kinase-MB averaged 917 ± 122.2 U L⁻¹, indicating myocardial injury. Histology revealed myocardial necrosis, interstitial edema, and vascular congestion.

Conclusion: Naja ashei venom exhibits high lethality and produces electrolyte imbalance and myocardial injury in a route-dependent manner. These findings support antivenom administration, electrolyte correction, intensive cardiac monitoring, and inclusion of Naja ashei venom in antivenom development to improve clinical outcomes.