Seed extract of <i>Annona muricata</i> reverses the reproductive toxicity and oxidative stress induced by cyclophosphamide in <i>drosophila melanogaster</i>

Cyclophosphamide, a widely used chemotherapeutic agent and immunosuppressant, is linked to significant oxidative stress and reproductive toxicities. While various strategies aim to mitigate these effects, the protective potential of <i>Annona muricata</i>, a plant with established anti-toxic properties, remains unexplored. This study investigated the ameliorative effects of the methanolic seed extract of <i>A. muricata</i> on cyclophosphamide-induced reproductive toxicity and oxidative stress in <i>Drosophila melanogaster</i>. The plant extract was obtained using standard methods, and the LC₅₀ was determined. Negative geotaxis, fecundity, and biochemical assays were performed. The LC₅₀ for cyclophosphamide and the plant extract were 3.96 and 6,889 mg/10 g diet, respectively. The number of emergent flies (fecundity), which was decreased by cyclophosphamide-induced toxicity, increased after treatment with the extract. Negative geotaxis improved from 30% after exposure to the toxicant to 60% after treatment with 100 mg per 10 g diet of the extract. After exposure to cyclophosphamide and treatment with the plant extract (100 mg/10 g diet), catalase and glutathione-S-transferase activities improved from 183 ± 36.6 μmol/min/mg protein and 0.377 ± 0.024 μmol/min/mg protein to 348 ± 28.9 μmol/min/mg protein and 0.668 ± 0.053 μmol/min/mg protein, respectively (<i>p</i> < 0.05). Total thiol levels, indicative of oxidative stress, were also restored after treatment with the extract. These findings highlight <i>A. muricata</i> seed extract's potential to mitigate cyclophosphamide-induced oxidative stress, neuromuscular impairments, and reproductive toxicity. Further research is needed to optimize dosing and elucidate the underlying protective mechanisms of <i>A. muricata</i> seed extract, supporting its therapeutic application in chemotherapy-induced toxicity.