An insight into the ameliorative effects of melatonin against chromium induced oxidative stress and DNA damage: a review

Abstract

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.

Chromium Induced Developments of Diseases and their Inhibitions by Cargos

“…(Na 2 Cr 2 O 7 ), chromium oxide (CrO 3 ), potassium chromate (K 2 CrO 4 ), and potassium dichromate (K 2 Cr 2 O 7 ), when exposed to humans mainly through the inhalation, dermal contact, and drinking water, causes the development of various diseases [1][2][3][4][5][6][7][8][9][10][11]. Cr normally exists in two stable oxidative states of hexavalent Cr-VI and trivalent Cr-III.…”

“…2+ react with biological molecules such as DNA, RNA, and proteins, leading to interferences with their normal activities, whereas tetrahedral Cr-VI complexes form oxyanions such as CrO 4 2or Cr 2 O 7 2-, which show their biological consequences but do not interact with macromolecules [1]. Cr-VI composites, upon exposure, can penetrate the cells through the sulfate-anion channels and are reduced to Cr-III compounds with the formation of highly reactive Cr-V and Cr-IV transitionals by the cellular reductants such as glutathiones (GSH) and ascorbates [11].…”

“….-) generating hydrogen peroxides (H 2 O 2 ), hydroxyl radicals, singlet oxygens and superoxides via the Fenton and Haber-Weiss type reactions [11,2]. Consequently, excessively generated reactive oxygen species (ROS) give rise to oxidative stress, overpowering body antioxidant and immune defense system, leading to DNA damage, including the formation of Cr-III-DNA adducts, DNA single and double -strand breaks, DNA-protein cross-links, cellular and sub-cellular damages as well as membrane lipid injuries affecting DNA replication, transcription, and translation, and resulting in genetic mutations and altered gene expressions -oriented carcinogenesis [11,2,8,12].…”

“….-) generating hydrogen peroxides (H 2 O 2 ), hydroxyl radicals, singlet oxygens and superoxides via the Fenton and Haber-Weiss type reactions [11,2]. Consequently, excessively generated reactive oxygen species (ROS) give rise to oxidative stress, overpowering body antioxidant and immune defense system, leading to DNA damage, including the formation of Cr-III-DNA adducts, DNA single and double -strand breaks, DNA-protein cross-links, cellular and sub-cellular damages as well as membrane lipid injuries affecting DNA replication, transcription, and translation, and resulting in genetic mutations and altered gene expressions -oriented carcinogenesis [11,2,8,12]. Though Cr-III compounds at lower concentrations, act as insulin enhancers for the type 2 diabetes, at higher concentrations, they can lead to DNA damage through their accumulations around the cells, altering the cellular surface morphology and entering into the cells via the reactions with the cellular reduction, which finally are converted to Cr-V by oxidation [11,1].…”

“…The application of external antioxidants, antibiotics, and anti-carcinogens may inhibit oxidative stress and disease progression by donating electrons, neutralizing free radicals, and blocking different pathways of diseasepromotion. Some cargos such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), quercetin, curcumin, melatonin, luteolin, vitamins C and E, selenium, propyl thiouracil, α-lipoic acid, pterostilbene, and boron compounds have been used to treat as recognized antioxidant, anti-inflammatory, and anti-cancer activities against Cr-VI-induced toxicities-related various diseases [14,15,2,[7][8][9][10][11]. This review chiefly elucidates the mechanistic development of various diseases by the exposure of chromium and the inhibitions of diseases by different cargos.…”