The pleiotropic role of melatonin against chromium-induced cardiovascular infirmities: a mechanistic insight

Abstract

Currently, cardiovascular diseases are still the number one killer in the world. These include hypertension, coronary heart disease, ischemic heart disease, myocardial infarction, congestive heart failure, cardiac arrhythmias, etc. One of the risk factors for cardiovascular diseases is environmental heavy metal pollution which makes the victims more vulnerable to sudden cardiac death. Chromium (Cr) is one of the metals. Cr(VI) is the most hazardous one among its variants.  It is readily across the plasma membrane to cause oxidative damage to intracellular molecules including LDL, proteins, and DNA; therefore, promotes endothelial dysfunction and Ca2+ overload in the heart. As to its molecular mechanism, Cr(VI) downregulates the expressions of SIRTUINS, FOXOs, PGC-1α, and AMPK and upregulates the P53, Akt, and NF-κβ, causing alteration in metabolic pathways, inhibiting mitochondrial biogenesis, inducing autophagy and apoptosis. In addition, Cr(VI) alters the expressions of Th1 cytokines (IL-1β, IL-2, IL-12, TNF-α, and IFN-γ) as well as Th2 cytokines (IL-4, IL-5, and IL-10) to induce myocardial inflammation. Melatonin, a potent antioxidant, and an efficient metal chelator can neutralize almost all the alterations caused by Cr(VI). Thus, melatonin can be a selected molecule to protect against Cr(VI)-induced cardiovascular toxicity. This review highlights the etiology of Cr(VI) associated heart diseases and the potentiality of melatonin to prevent Cr(VI)-mediated cardiac oxidative stress, apoptosis and inflammation.