Department of Physiology, College of Medicine, Ladoke Akintola University of Technology, Ogbomoso, Oyo, Nigeria.
Department of Physiology, College of Medicine, Ladoke Akintola University of Technology, Ogbomoso, Oyo, Nigeria; Reproductive Biology and Toxicology Research Laboratories, Oasis of Grace Hospital, Osogbo, Osun, Nigeria; Department of Chemical Sciences, Kings University, Odeomu, Osun, Nigeria.
Biomed Pharmacother. 2021 Jun;138:111443. doi: 10.1016/j.biopha.2021.111443. Epub 2021 Mar 2.
Dichlorvos is a known risk factor for organ toxicity. The liver and kidney are essential metabolic tissues but it is unclear whether or not there is associated redox dyshomeostasis in both organs in physiological and pathological states. Uric acid accumulation and glutathione dysregulation have been implicated in the aetiopathogenesis of organ damage. The antioxidant potentials of L-arginine have been shown in various conditions. The present study was thus designed to investigate the synchrony in hepatic and renal uric acid and glutathione status in dichlorvos-induced hepatorenal damage and to probe the possible therapeutic role of L-arginine. Twenty-one male Wistar rats were treated with standard rat diet and water, dichlorvos, or dichlorvos and L-arginine. Our findings revealed that dichlorvos significantly impaired hepatic and renal functions, increased hepatic and renal malondialdehyde, but reduced glutathione and activities of superoxide dismutase, catalase, and glutathione peroxidase. These events were accompanied by increased accumulation of plasma, hepatic, and renal uric acid as well as reduced body weight gain, and hepatic and renal weights. Histopathological examinations revealed hepatic and renal architectural derangement and cellular necrosis and degeneration in dichlorvos-exposed rats. Interestingly, L-arginine reversed dichlorvos-induced systemic, hepatic and renal synchronous redox dyshomeostasis. L-arginine administration also improved hepatic and renal cytoarchitecture. It is thus concluded that dichlorvos triggered synchronous uric acid generation and glutathione alterations in the liver and kidney. L-arginine confers protection against dichlorvos-induced hepatorenal damage via suppression of uric acid generation and blockade of glutathione dysregulation.
敌敌畏是一种已知的器官毒性风险因素。肝脏和肾脏是重要的代谢组织，但在生理和病理状态下，这两个器官是否存在相关的氧化还原失衡尚不清楚。尿酸积累和谷胱甘肽失调与器官损伤的发病机制有关。在各种情况下，L-精氨酸的抗氧化潜力已经得到证实。因此，本研究旨在探讨敌敌畏诱导的肝肾功能损伤中肝肾功能尿酸和谷胱甘肽状态的同步性，并探讨 L-精氨酸的可能治疗作用。21 只雄性 Wistar 大鼠用标准大鼠饲料和水、敌敌畏或敌敌畏和 L-精氨酸处理。我们的研究结果表明，敌敌畏显著损害了肝肾功能，增加了肝肾功能丙二醛，但降低了谷胱甘肽和超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性。这些事件伴随着血浆、肝脏和肾脏尿酸的积累增加以及体重增加、肝脏和肾脏重量的减少。组织病理学检查显示，敌敌畏暴露的大鼠肝脏和肾脏结构紊乱，细胞坏死和变性。有趣的是，L-精氨酸逆转了敌敌畏诱导的全身、肝脏和肾脏同步氧化还原失衡。L-精氨酸的给药还改善了肝肾功能的细胞结构。因此，结论是敌敌畏引发了肝脏和肾脏中尿酸生成和谷胱甘肽改变的同步性。L-精氨酸通过抑制尿酸生成和阻断谷胱甘肽失调来对抗敌敌畏诱导的肝肾功能损伤。
