Department of Pharmaceutical Sciences, College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Biomolecules. 2021 Oct 23;11(11):1575. doi: 10.3390/biom11111575.
Cadmium is a nonessential metal that has heavily polluted the environment due to human activities. It can be absorbed into the human body via the gastrointestinal tract, respiratory tract, and the skin, and can cause chronic damage to the kidneys. The main site where cadmium accumulates and causes damage within the nephrons is the proximal tubule. This accumulation can induce dysfunction of the mitochondrial electron transport chain, leading to electron leakage and production of reactive oxygen species (ROS). Cadmium may also impair the function of NADPH oxidase, resulting in another source of ROS. These ROS together can cause oxidative damage to DNA, proteins, and lipids, triggering epithelial cell death and a decline in kidney function. In this article, we also reviewed evidence that the antioxidant power of plant extracts, herbal medicines, and pharmacological agents could ameliorate cadmium-induced kidney injury. Finally, a model of cadmium-induced kidney injury, centering on the notion that oxidative damage is a unifying mechanism of cadmium renal toxicity, is also presented. Given that cadmium exposure is inevitable, further studies using animal models are warranted for a detailed understanding of the mechanism underlying cadmium induced ROS production, and for the identification of more therapeutic targets.
镉是一种非必需的重金属，由于人类活动而严重污染了环境。它可以通过胃肠道、呼吸道和皮肤被人体吸收，会对肾脏造成慢性损害。镉在肾单位中蓄积并造成损伤的主要部位是近端肾小管。这种蓄积会诱导线粒体电子传递链功能障碍，导致电子泄漏和活性氧（ROS）的产生。镉还可能损害 NADPH 氧化酶的功能，从而产生另一种 ROS 来源。这些 ROS 共同作用会导致 DNA、蛋白质和脂质的氧化损伤，引发上皮细胞死亡和肾功能下降。本文还综述了植物提取物、草药和药理学药物的抗氧化能力可以改善镉诱导的肾损伤的证据。最后，提出了一个以氧化损伤为镉肾毒性统一机制的镉诱导肾损伤模型。鉴于镉暴露是不可避免的，需要使用动物模型进行进一步研究，以深入了解镉诱导 ROS 产生的机制，并确定更多的治疗靶点。
