Mechanism of chromium-induced toxicity in lungs, liver, and kidney and their ameliorative agents

Heavy metal Chromium (Cr), can adversely affect humans and their health if accumulated in organs of the body, such as the lungs, liver, and kidneys. Cr (VI) is highly toxic and has a higher solubility in water than Cr (III). One of the most common routes for Cr exposure is through inhalation and is associated with liver, lung, kidney damage, widespread dermatitis, GI tract damage, human lung cancer, cardiomyopathies, and cardiovascular disease. The increase in ROS production has been attributed to most of the damage caused by Cr toxicity. Crinduced ROS-mediated oxidative stress has been seen to cause a redox imbalance affecting the antioxidant system balance in the body. The Nrf2 pathway dysregulation has been implicated in the same. Deregulation of histone acetylation and methylation has been observed, together with gene methylation in genes such as p16, MGMT, APC, hMLH1, and also miR-143 repression. Several ultra-structural changes have been observed following Cr (VI)-toxicity, including rough ER dilation, alteration in the mitochondrial membrane and nuclear membrane, pycnotic nuclei formation, and cytoplasm vacuolization. A significant change was observed in the metabolism of lipid, glucose, and the metabolism of protein after exposure to Cr. Cr-toxicity also leads to immune system dysregulations with changes seen in the expression of IL-8, IL-4, IgM, lymphocytes, and leukocytes among others. P53, as well as pro-and anti-apoptotic proteins, are involved in apoptosis. These Cr-induced damages can be alleviated via agents that restore antioxidant balance, regulate Nrf-2 levels, or increase anti-apoptotic proteins while decreasing pro-apoptotic proteins.