Oxidative Stress and Its Role in Cd-Induced Epigenetic Modifications: Use of Antioxidants as a Possible Preventive Strategy

Abstract

Oxidative stress (OS) represents one of the main mechanisms of toxicity induced by environmental pollutants such as cadmium (Cd). OS is a natural physiological process where the presence of oxidants, such as reactive oxygen-derived species (ROS), outweighs the strategy of antioxidant defenses, culminating in the interruption of signaling and redox control. It has been suggested that Cd increases ROS mainly by inducing damage to the electron transport chain and by increasing the activity of nicotinamide adenine dinucleotide hydrogen phosphate (NADPH) oxidase (NOX) and the concentration of free iron (Fe), as well as causing a decrease in antioxidant defense. On the other hand, OS has been related to changes in the biology of the epigenome, causing adverse health effects. Recent studies show that Cd generates alterations in deoxyribonucleic acid (DNA) methylation, histone modifications, and noncoding RNA (ncRNA) expression. However, the role of OS in Cd-induced epigenetic modifications is still poorly explored. Therefore, this review provides an update on the basic concepts of OS and its relationship with Cd-induced epigenetic changes. Furthermore, the use of antioxidant compounds is proposed to mitigate Cd-induced epigenetic alterations.

Heavy metals toxicity on epigenetic modifications in the pathogenesis of Alzheimer's disease (AD)

“…[101,102] When Cd exposure occurs, there is an increased TET expression with less expression of DNMT activity causing hypomethylation, whereas Cd also increases DNMT1 and DNMT3A expression thereby leading to hypermethylation. [103] This discrepancy of Cd on DNA methylation depends on duration and level of exposure. In AD, the methylation induces promoter CDK5 hypomethylation of APP, PSEN1, PSEN2, and GSK3β genes and also, hypermethylation of ANK1, RPL13, RHBDF2, DUSP22, and SORL1 genes.…”

“…However, minimal research has been focused on Cd exposure affecting histone methylation, acetylation, and phosphorylation by changing the enzyme expression that alters them. [ 103 ] In vitro investigations have primarily been used to describe Cd‐induced histone changes. At the metallothionein 3 (MT3) promoter region, Cd‐exposed cells had higher levels of H3K4me3, H3K27me3, and H3K9me3.…”

Cadmium Exposure: Mechanisms and Pathways of Toxicity and Implications for Human Health

“…For example, research on liver cells revealed that Cd treatment significantly decreased the activities of SOD and CAT and increased the levels of lipid peroxidation products, demonstrating how Cd aggravates oxidative stress by impairing the antioxidant enzyme system [ 40 ]. Additionally, Cd inhibits the synthesis and promotes the depletion of glutathione (GSH), a crucial intracellular antioxidant molecule, further reducing intracellular GSH levels and weakening the antioxidant capacity of cells [ 41 ].…”

Improving hydrocarbon toxicity tolerance in poultry: role of genes and antioxidants

“…Hong and Gurjit (2012) assert that exposure to particulate matter can induce glutathione depletion in the methylation cycle, thereby promoting epigenetic changes, whereas Madrigano et al (2012) established that PAHs form adducts inducing DNA methylation (hypo and hyper) of specific genes linked to physiological dysfunctions and contribute more to the occurrence and development of diseases ( Cao et al, 2020 ). Hernández-Cruz et al (2022) also reviewed cadium-induced epigenetic alterations and the use of antioxidant compounds to counteract Cd-induced epigenetic alterations.…”