Abstract
BACKGROUND/AIM: Despite the known harmful effects associated with malathion toxicity in various organs, it continues to be widely used for plant protection and insect control. This study is the first to compare the protective effects of estradiol and ascorbic acid against malathion-induced nephrotoxicity through histopathological assessment and molecular docking analyses. MATERIALS AND METHODS: This study was conducted using 20 female albino rats that were distributed into sham, malathion, malathion + estradiol, and malathion + ascorbic acid groups. Nephrotoxicity was induced by daily treatment with malathion and the effects of estradiol and ascorbic on nephrotoxicity were evaluated. After 4 weeks of treatment, the animals were sacrificed and the kidneys were examined following hematoxylin and eosin (H&E) staining. Histopathology results were supported by molecular docking studies of estradiol and ascorbic acid against a target protein (PDB ID: 2YMX), the peptide inhibitor Fab408 inhibiting acetylcholinesterase (AChE). The inhibition of AChE is the primary mechanism of the toxic effects of malathion. RESULTS: Histopathological examination revealed a notable elevation (p < 0.001) in degeneration and necrosis within the tubular epithelium and interstitial nephritis in the malathion group compared to the sham group. Daily administration of estradiol and ascorbic acid resulted in a notable reduction (p = 0.0022) in the severity of these histopathological changes in the malathion + estradiol and malathion + ascorbic acid groups compared to the malathion group. Of these, the most significant decreases were observed in the malathion + ascorbic acid group. Docking studies of these compounds against the selected protein (PDB ID: 2YMX) revealed promising binding scores. Ascorbic acid exhibited the highest docking score (-6.44 kcal/mol), indicating a favorable binding interaction with this protein. CONCLUSION: Estradiol and ascorbic acid exert protective effects against malathion-induced nephrotoxicity, whereas ascorbic acid showed superior efficacy compared to estradiol. This result was further supported by molecular docking studies.