Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure

Abstract

Oxidative stress contributes to the pathophysiology of exposure to heavy metals/metalloid. Beneficial renal effects of some medications, such as chelation therapy depend at least partially on the ability to alleviate oxidative stress. The administration of various natural or synthetic antioxidants has been shown to be of benefit in the prevention and attenuation of metal induced biochemical alterations. These include vitamins, N-acetylcysteine, alpha-lipoic acid, melatonin, dietary flavonoids and many others. Human studies are limited in this regard. Under certain conditions, surprisingly, the antioxidant supplements may exhibit pro-oxidant properties and even worsen metal induced toxic damage. To date, the evidence is insufficient to recommend antioxidant supplements in subject with exposure to metals. Prospective, controlled clinical trials on safety and effectiveness of different therapeutic antioxidant strategies either individually or in combination with chelating agent are indispensable. The present review focuses on structural, chemical and biological aspects of antioxidants particularly related to their chelating properties.

Figure 1

Redox reaction showing generation of various Reactive Oxygen Species (ROS).

Figure 2

Effects of ROS on DNA damage leading to its role in carcinogenesis.

Figure 3

Enzymatic and non enzymatic classification of antioxidants with few.

Figure 4

Conversion of ascorbic acid into different reduced forms at various pH indicating possible binding sites and free electrons responsible for their antioxidant and chelating property.

Figure 5

Chemical structure of α-tocopherol and α-tocotrienol indicating isoprenoid units.

Figure 6

Oxidized and reduced form of lipoic acid showing presence of thiol groups as the possible metal chelating sites.

Figure 7

Reduced form of lipoic acid showing metal chelation at thiol groups (M = Cu²⁺, Zn²⁺, Cd²⁺, Pb²⁺, Hg²⁺ and Fe³⁺).

Figure 8

Structure of N-acetyl cysteine (NAC) depicting (1) two chelating sites (thiol and hydroxyl) and (2) deacetylation responsible for its antioxidant potential due to the generation of glutathione.

Figure 9

Structure of taurine showing sulfonate group as an electrophilic and amide group as a nucleophilic center responsible for it chelating and antioxidant properties, respectively.

Figure 10

Structure of quercetin showing coordination through the ortho-phenolic groups located on the B ring.

Figure 11

Structure of Quercetin-3-O-β-glucoside, a naturally occuring predominat form of Glycosylated Quercetin.

Figure 12

Structures of major constituents of garlic depicting thiol and amino moieties (the possible sites for metal chelation) along with the ketonic, sulphonic and hydroxyl groups (responsible for their antioxidant activity).