Influence of Dose and Route-Dependent Hepatotoxicity and Nephrotoxicity of Natural and Artificial Bee Venom (Apis mellifera) in Mice

Abstract

Bee venom (Apis mellifera) contains bioactive compounds such as melittin and phospholipase A₂, which have been reported to exert both therapeutic and toxic effects on various organs. This study aimed to evaluate the toxicity of natural and artificial bee venom on liver and kidney tissues in mice. Forty adult male albino mice were randomly assigned to five groups: control, natural bee venom (NBV) for 5 and 7 doses via stinging, and artificial bee venom (ArBV) for 5 and 7 doses via intraperitoneal injection. At the end of the exposure period, liver and kidney tissues were collected for histopathological analysis using hematoxylin and eosin (H&E) and Mallory’s trichrome stains. Histopathological examination revealed dose- and duration-dependent changes in both liver and kidney tissues. In the liver, NBV and ArBV exposure caused congestion, inflammatory infiltration, Kupffer cell hypertrophy, hepatocellular activation, and focal degenerative changes, with more pronounced effects in seven-dose groups. In the kidneys, NBV induced proximal tubular degeneration and necrosis, whereas ArBV caused mild tubular alterations with inflammatory infiltration. No severe systemic toxicity or organ failure was observed at the administered doses. Both natural and artificial bee venom exhibit organ-specific toxic effects in mice, particularly at higher doses and prolonged exposure. The liver and kidneys are primary target organs, and the severity of histological alterations depends on dose, exposure duration, and administration route. These findings highlight the importance of careful dose selection in therapeutic applications of bee venom and underscore its dual role as a toxic and potentially therapeutic agent