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Review
. 2014;2014:640754.
doi: 10.1155/2014/640754. Epub 2014 Aug 12.

Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems

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Free PMC article
Review

Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems

Bechan Sharma et al. Biomed Res Int. .
Free PMC article

Abstract

Several workers have extensively worked out the metal induced toxicity and have reported the toxic and carcinogenic effects of metals in human and animals. It is well known that these metals play a crucial role in facilitating normal biological functions of cells as well. One of the major mechanisms associated with heavy metal toxicity has been attributed to generation of reactive oxygen and nitrogen species, which develops imbalance between the prooxidant elements and the antioxidants (reducing elements) in the body. In this process, a shift to the former is termed as oxidative stress. The oxidative stress mediated toxicity of heavy metals involves damage primarily to liver (hepatotoxicity), central nervous system (neurotoxicity), DNA (genotoxicity), and kidney (nephrotoxicity) in animals and humans. Heavy metals are reported to impact signaling cascade and associated factors leading to apoptosis. The present review illustrates an account of the current knowledge about the effects of heavy metals (mainly arsenic, lead, mercury, and cadmium) induced oxidative stress as well as the possible remedies of metal(s) toxicity through natural/synthetic antioxidants, which may render their effects by reducing the concentration of toxic metal(s). This paper primarily concerns the clinicopathological and biomedical implications of heavy metals induced oxidative stress and their toxicity management in mammals.

Figures

Figure 1
Figure 1
Reactive oxygen species (ROS) existing in radicals and nonradicals forms.
Figure 2
Figure 2
Effect of activation by arsenate (As(V)) and arsenite (As(III)) on the signal transduction pathways. As(V) and As(III) activate different proteins to regulate c-Jun N-terminal kinase (JNK), which functions in the stress-activated protein kinase pathway (SAPK). A SAPK pathway is a sequential protein kinase cascade where mitogen-activated protein (MAP) kinase kinase kinase kinase (MAP4 K) phosphorylates and activates a MAP kinase kinase kinsase (MAP3 K), which repeats the cycle by phosphorylating and activating the next kinase in the cascade. The small GTP binding proteins (G-proteins: Ras, Rac, Cdc-42, and Rho) are localized upstream of the sequential protein kinase cascade. The anion transport protein regulates entry of arsenate into the cell, while arsenite, which is an uncharged arsenic species, enters the cell by diffusion. The small G-proteins that are regulated by As(V) and As(III) do not appear to play a significant role in As(V) and As(III) signaling to JNK. The p-21-activated kinase (PAK) plays a role in As(III)-dependent JNK activity. MEKK3 and MEKK4 are involved in both As(V) and As(III) activation of JNK, while MEKK2 may be involved in the activation of JNK by As(III) (Porter et al.) [6].

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