Cadmium-Induced Kidney Injury: Oxidative Damage as a Unifying Mechanism

Abstract

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.

Cadmium-Induced Kidney Injury in Mice Is Counteracted by a Flavonoid-Rich Extract of Bergamot Juice, Alone or in Association with Curcumin and Resveratrol, via the Enhancement of Different Defense Mechanisms

“…As consequence, the expression levels of downstream Nrf2 signaling genes Hmox1 and Nqo1 were up-regulated. Our results are clearly consistent with previous research, wherein the administration of Cd significantly increased the expression of Nrf2 and further upregulated the expression of downstream phase II detoxification enzymes [ 77 , 78 ]. This result further confirms that Nrf2-ARE signaling is a crucial regulator for cells to maintain the oxidant/antioxidant balance.…”

Toxic Effects of Cadmium on Fish

“…Combined, all of these factors will further affect the function of enzymes related to regulating cell proliferation and differentiation and apoptosis on the membrane, finally causing a series of functional disorders and damage to the body [ 94 , 143 , 144 ]. The increase in intracellular ROS caused by Cd mainly occurs through the following pathways: (I) Cd affects cellular respiration by inhibiting the respiratory transmission chain in the mitochondria, resulting in an increase in byproduct ROS content [ 145 ]; (II) Cd can increase ROS content by increasing the activity of nitric oxide synthase and the expression level of the related genes in the body [ 146 ]; (III) Cd can also remove Ca, Cu, Fe, and other elements from the binding proteins in the cell, thereby causing an increase in calcium, copper, iron, and other elements in the cytoplasm, resulting in oxidative stress and an increase in intracellular ROS content [ 147 , 148 ]; (IV) Cd reduces the antioxidant capacity of cells by reducing the activity of intracellular antioxidant enzymes ( Figure 2 ) [ 143 , 149 ].…”

Renoprotective and Oxidative Stress-Modulating Effects of Taxifolin against Cadmium-Induced Nephrotoxicity in Mice

“…Metal mining, refining, smelting, fossil fuel burning, and rubbish burning all contribute to prevalent Cd contamination [ 6 ]. Furthermore, feedstuffs, drinking water, inspired cigarette smoke or polluted air, and absorption of polluted soil and dust created by people and animals that have earlier collected Cd in their biological cells are also causes of Cd exposure [ 7 ]. Indeed, Cd is a non-biodegradable, poisonous element with a prolonged biological half-life and is harmful to plants, humans, and animals [ 8 ].…”