Chromium (Cr), a ubiquitous metal, has become a potent pollutant due to global industrialization, leading to pollution of air, water, and food that impacts human health. The most stable forms of Cr are Cr(III) and Cr(VI) (the major product of industrial activities). Cr(III) is a micronutrient essential for maintaining normal blood glucose and lipid profiles in our body but it can also form Cr (III)-DNA adducts. In addition, it directly produces reactive oxygen species (ROS) via Fenton and Haber-Weiss reactions; leading to tissue injuries. Cr (VI) has the capacity to generate Cr(V), Cr (IV), and Cr(III), respectively under suitable conditions. These intermediates also damage to biological macromolecules by interactions with several enzymatic and non-enzymatic antioxidants. For example, Cr(III) can make double DNA strands breaking to inhibit DNA replication, induce DNA oxidation, and DNA adducts formation. All of these lead to the development of malignancy. Melatonin, a potent radical scavenger as well as a metal chelator, effectively chelates Cr(VI) and prevents DNA oxidative damage. Melatonin can upregulate the gene expression of several antioxidant enzymes, and thereby, maintains cellular integrity from the oxidative stress. Thus, melatonin can be a prime molecule to protect against Cr(VI) induced cytotoxicity and genotoxicity. This review aims to highlight the potential benefits of melatonin on Cr(VI) induced oxidative stress and DNA damage.

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In the current study, it was found that high fat diet (60% of total kCal) (H) or/and isoproterenol (I) exacerbated oxidative stress and caused myocardial damage. This was indicated by increased levels of LPO, PCO, abnormal mitochondria and altered activities of metabolic as well as antioxidant enzymes in myocardium of rats. Melatonin at different doses (10, 20 and 40 mg/kg) effectively protected against myocardial damage induced by H or/and I and preserved all of these altered parameters. Morphological analyses showed that combination of H and I treatment led to the extensive myofibril disintegration and neutrophil infiltration. Melatonin at the dose of 40 mg/kg almost completely prevented these pathological alterations. The mechanistical studies have uncovered that the protective effects of melatonin on the myocardial damage induced by H and I are attributed to its direct and indirect antioxidative capacity, i.e., it directly scavenges free radicals and also regulates the gene expression of antioxidant enzymes. Collectively, based on the evidences gathered from the current study, it will not be unwise to suggest that melatonin can serve as an ideal therapeutic agent for those cardiovascular diseases caused by oxidative stress.

In recent days, the hike in obesity-mediated epidemics across the globe and the prevalence of obesity-induced cardiovascular disease has become one of the chief grounds for morbidity and mortality. This epidemic-driven detrimental events in the cardiac tissues start with the altered distribution and metabolism pattern of high-density lipoprotein and low-density lipoprotein (LDL) leading to cholesterol (oxidized LDL) deposition on the arterial wall and atherosclerotic plaque generation, followed by vascular spasms and infarction. Subsequently, obesitytriggered metabolic malfunctions induce free radical generation which may further trigger pro-inflammatory signaling and nuclear factor kappa-light-chainenhancer of activated B cells transcriptional factor, thus inducing interferongamma, tumor necrosis factor-alpha, and inducible nitric oxide synthase. This terrifying cardiomyopathy can be further aggravated in type 2 diabetes mellitus, thereby making obese diabetic patients prone toward the development of myocardial infarction (MI) or stroke in comparison to their nondiabetic counterparts. The accelerated oxidative stress and pro-inflammatory response induced cardiomyocyte hypertrophy, followed by apoptosis in obese diabetic individuals, causing progression of athero-thrombotic vascular disease. Being an efficient antioxidative and anti-inflammatory indolamine, melatonin effectively inhibits lipid peroxidation, pro-inflammatory reactions, thereby resolving free radical-induced myocardial damages along with maintaining antioxidant reservoir to preserve cardiovascular integrity. Prolonged melatonin treatment maintains balanced body weight and serum total cholesterol concentration by inhibiting cholesterol synthesis and promoting cholesterol catabolism. Additionally, melatonin promotes macrophage polarization toward the anti-inflammatory state, providing a proper shield during the recovery period. Therefore, the protective role of melatonin in maintaining the lipid metabolism homeostasis and blocking the atherosclerotic plaque rupture could be targeted as the possible therapeutic strategy for the management of obesity-induced acute MI. This

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.

Cardiovascular disease (CVD) is a global health concern due to its high mortality. Heavy metals are the potential risk factor for CVD. Among other heavy metals, chromium (Cr) is considered a serious threat to human health due to its high oxidative capacity. In the current study, male Wistar rats were treated with Cr to induce cardiac tissue injuries, meanwhile, melatonin was given to test whether this treatment can protect against Cr-induced cardiac damage. The results showed that Cr markedly altered the heart weight, biomarkers of oxidative stress, activities of antioxidant and pro-oxidant enzymes, as well as tissue morphology. On contrary, melatonin treatment significantly suppressed all these alterations via its antioxidant activity. In addition, melatonin also significantly reduced tissue Cr concentration probably through its metal-chelating activity. The current study has demonstrated that melatonin is a promising antioxidant to protect the heart from Cr-induced oxidative damage, confirming that melatonin can be a future therapeutic agent for Cr-mediated toxicity in the heart or other organs.