Althobaiti Saed A
Department of Biology, Turabah University College, Taif University, Turabah, Taif, Mecca 21995, Saudi Arabia.
Mol Med Rep. 2025 Nov;32(5). doi: 10.3892/mmr.2025.13661. Epub 2025 Aug 24.
Malathion, a commonly used organophosphate pesticide, induces severe hepatorenal toxicity, mitochondrial dysfunction and inflammatory responses primarily through oxidative stress and apoptosis. The present study investigated the protective effects of mitoquinol (MitoQ), a mitochondria‑targeted antioxidant, against malathion‑induced toxicity in male Wistar albino rats. A total of 50 rats were divided into the following five groups: i) Control; ii) malathion‑only; iii) malathion + MitoQ; iv) MitoQ‑only; and v) vehicle. Malathion exposure significantly elevated the levels of aspartate aminotransferase, alkaline phosphatase, creatinine, urea and uric acid and decreased total protein, albumin and globulin levels. At the mitochondrial level, malathion reduced antioxidant enzyme activity (superoxide dismutase, glutathione peroxidase and glutathione) and ATP production while increasing reactive oxygen species, leading to oxidative damage. Furthermore, malathion induced upregulation of pro‑apoptotic markers such as Bax, and downregulation of the anti‑apoptotic marker, Bcl‑2. In addition, malathion increased TNF‑α, NF‑κB, Toll‑like receptor (TLR) 2 and TLR4 expression, and malathion toxicity induced severe hepatorenal damage, including vascular congestion, inflammatory infiltration and tubular degeneration. MitoQ co‑administration revealed a trend towards mitigating altered hepatorenal markers, inflammatory markers and regulated apoptotic/antiapoptotic gene markers, with partial restoration in mitochondrial function and histopathological changes. In parallel, MitoQ normalized cellular changes induced by malathion in the liver and kidneys. In conclusion, malathion toxicity in the liver and kidneys is mediated by mitochondrial oxidative stress, apoptosis and inflammation. MitoQ exerts protective effects by restoring mitochondrial homeostasis, reducing inflammatory signaling and mitigating tissue damage. Future research should explore longer treatment durations and potential synergistic effects with other antioxidants to optimize protection against pesticide‑induced toxicity.
马拉硫磷是一种常用的有机磷农药，主要通过氧化应激和细胞凋亡诱导严重的肝肾毒性、线粒体功能障碍和炎症反应。本研究调查了线粒体靶向抗氧化剂米托蒽醌（MitoQ）对雄性Wistar白化大鼠马拉硫磷诱导的毒性的保护作用。总共50只大鼠被分为以下五组：i）对照组；ii）仅马拉硫磷组；iii）马拉硫磷+MitoQ组；iv）仅MitoQ组；v）赋形剂组。马拉硫磷暴露显著提高了天冬氨酸转氨酶、碱性磷酸酶、肌酐、尿素和尿酸水平，并降低了总蛋白、白蛋白和球蛋白水平。在线粒体水平上，马拉硫磷降低了抗氧化酶活性（超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽）和ATP生成，同时增加了活性氧，导致氧化损伤。此外，马拉硫磷诱导促凋亡标志物如Bax上调，抗凋亡标志物Bcl-2下调。此外，马拉硫磷增加了TNF-α、NF-κB、Toll样受体（TLR）2和TLR4的表达，并且马拉硫磷毒性诱导了严重的肝肾损伤，包括血管充血、炎症浸润和肾小管变性。联合给予MitoQ显示出减轻肝肾标志物改变、炎症标志物以及调节凋亡/抗凋亡基因标志物的趋势，线粒体功能和组织病理学变化部分恢复。同时，MitoQ使马拉硫磷诱导的肝脏和肾脏细胞变化正常化。总之，肝脏和肾脏中的马拉硫磷毒性是由线粒体氧化应激、细胞凋亡和炎症介导的。MitoQ通过恢复线粒体稳态、减少炎症信号传导和减轻组织损伤发挥保护作用。未来的研究应探索更长的治疗持续时间以及与其他抗氧化剂的潜在协同作用，以优化对农药诱导毒性的保护。
