Alhilal Mohammad, Elsayed Mohamed Salem Mahmoud, Ali Albakoush Ahmed, Alhilal Suzan, Farag Basant, Gomha Sobhi M
Department of Nursing, Faculty of Health Sciences, Mardin Artuklu University, Mardin, Turkiye.
Department of Pathology, Faculty of Medicine, Alasmarya Islamic University, Zliten, Libya.
Turk J Med Sci. 2024 Oct 29;55(1):337-345. doi: 10.55730/1300-0144.5974. eCollection 2025.
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.
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.
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.
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.
背景/目的：尽管已知马拉硫磷对各器官的毒性有害，但它仍被广泛用于植物保护和虫害控制。本研究首次通过组织病理学评估和分子对接分析，比较雌二醇和抗坏血酸对马拉硫磷诱导的肾毒性的保护作用。
本研究使用20只雌性白化大鼠，分为假手术组、马拉硫磷组、马拉硫磷+雌二醇组和马拉硫磷+抗坏血酸组。通过每日给予马拉硫磷诱导肾毒性，并评估雌二醇和抗坏血酸对肾毒性的影响。治疗4周后，处死动物，对肾脏进行苏木精-伊红（H&E）染色检查。组织病理学结果得到雌二醇和抗坏血酸针对靶蛋白（PDB ID：2YMX）的分子对接研究的支持，该肽抑制剂Fab408抑制乙酰胆碱酯酶（AChE）。AChE的抑制是马拉硫磷毒性作用的主要机制。
组织病理学检查显示，与假手术组相比，马拉硫磷组肾小管上皮细胞变性和坏死以及间质性肾炎显著增加（p < 0.001）。与马拉硫磷组相比，每日给予雌二醇和抗坏血酸导致马拉硫磷+雌二醇组和马拉硫磷+抗坏血酸组这些组织病理学变化的严重程度显著降低（p = 0.0022）。其中，马拉硫磷+抗坏血酸组的降低最为显著。这些化合物针对所选蛋白（PDB ID：2YMX）的对接研究显示出有前景的结合分数。抗坏血酸表现出最高的对接分数（-6.44 kcal/mol），表明与该蛋白有良好的结合相互作用。
雌二醇和抗坏血酸对马拉硫磷诱导的肾毒性具有保护作用，而抗坏血酸的疗效优于雌二醇。分子对接研究进一步支持了这一结果。
