Iorjiim_2026_Toxicol.Rep_17_102301

Efavirenz acts against human immunodeficiency virus (HIV-1), induces functional senescence, and increases mortality in Drosophila melanogaster (Fruit fly). Kaempferol is a plant-derived flavonoid with neuroprotective and antioxidant properties. This study evaluated the protective effect of Kaempferol on efavirenz-induced functional senescence in D. melanogaster. Kaempferol was isolated from Moringa oleifera leaves. Adult flies (24-72 h old) were exposed to graded concentrations (1-1000 mg/10 g diet) to determine the median lethal concentration (LC50). Sublethal doses (5-50 mg/10 g diet) were used to assess longevity, acute toxicity, fecundity, locomotor performance, and biochemical parameters. For protective evaluation, flies were co-treated with efavirenz (5 mg/10 g diet) and kaempferol (10 or 20 mg/10 g diet) for 7 days. Survival, climbing ability, fecundity, antioxidant biomarkers, and acetylcholinesterase activity were subsequently measured. Kaempferol showed an LC(50) of 338.60 mg/10 g diet. Additionally, it significantly improved survival, climbing ability, and reproductive capacity compared to control flies (P < 0.05). It also enhanced the antioxidant status in flies, as evidenced by a significant (P < 0.05) increase in total thiol levels, as well as glutathione S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) activities, alongside a decrease in malondialdehyde (MDA) concentration. Furthermore, Kaempferol mitigated efavirenz-induced mortality, climbing weakness, reproductive decline, and deficits in acetylcholinesterase (AChE) activity (P < 0.05). Overall, this study demonstrated the chemoprotective potential of Kaempferol against efavirenz-induced mortality and functional senescence in D. melanogaster through antioxidative mechanisms. This, to the best of our knowledge, has not been reported before.