Abstract
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 Annona muricata, a plant with established anti-toxic properties, remains unexplored. This study investigated the ameliorative effects of the methanolic seed extract of A. muricata on cyclophosphamide-induced reproductive toxicity and oxidative stress in Drosophila melanogaster. 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 (p < 0.05). Total thiol levels, indicative of oxidative stress, were also restored after treatment with the extract. These findings highlight A. muricata 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 A. muricata seed extract, supporting its therapeutic application in chemotherapy-induced toxicity.