ANTIOXIDANTS, FREE RADICALS and LONGEVITY

Antioxidant and Vitamins

Introduction

Antioxidants are compounds that inhibit oxidation. The end product of oxidation are free radicals that can damage cells and tissues of organisms. Antioxidants such as ascorbic acid (AA; vitamin C) terminate these chain reactions. To balance the overproduction of free radicals, organisms maintain complex systems of overlapping antioxidants. Among those produced internally are glutathione, the enzymes catalase, superoxide dismutase and glutathione peroxidase. Dietary antioxidants include vitamins C and E. The latter is composed of several fat-soluble molecules (α-, β-, γ-, and δ-tocopherol and α-, β-, γ-, and δ-tocotrienol). They are generally found in vegetable oils, nuts, whole grains, and green leafy vegetables. The most nutritionally potent form of the E vitamin group is α-tocopherol.

Vitamin E

Vitamin E , a potent vitamin antioxidant, quenches the self-perpetuating cycle of lipid peroxidation: that is, the oxidation of lipids to produce a peroxide. In this process, free radicals are generated which abstract electrons from cell membrane lipids causing cell damage.
Apparently, vitamin E can protect against cardiovascular diseases (CVDs) using four different ways. In vitro studies show that vitamin E prevents the abnormal proliferation of vascular smooth muscle cells (VSMC). Aberrant proliferation of these cells arguably leads to plaque formation in the arteries. It also protects against free radical damage, which has been implicated in aging, cancer, and atherosclerosis. α -Tocopherol inhibits phosphokinase C (PKC) – a family of enzymes which regulates immune responses and cell growth. Because of its roles in regulating cell growth, inhibition of VSMC proliferation represents a physiological mechanism whereby diseased states such as atherosclerosis can be prevented. Also, contributing to the development of atherosclerosis are macrophage/monocytes class of white blood cells (WBCs). These white blood WBCs transition into foam cells which are formed when fat is deposited in the blood vessel walls. Consequently, they appear foamy – an essential first step towards the formation atherosclerotic plaques. Both in vivo as well as in vitro studies have shown that vitamin E inhibits foam cell formation and thus plaque formation.
Intercellular adhesion molecule-1 (ICAM-1), activates the binding of WBCs to the cells lining the blood vessels (endothelial cells) via ICAM-1. More than this, ICAM-1 enables the recruitment of inflammatory WBCs. They bind to the inner lining of the blood vessels (endothelium) resulting in plaque formation. Significantly, WBC recruitment in vivo is inhibited by α-tocopherol, consequently reducing plaque formation.
Whereas ICAM-1 is primarily involved in atherosclerosis, vascular cell adhesion molecule 1 (VCAM-1) is contributes to both atherosclerosis and arthritis. VCAM-1 also regulates adhesion of WBCs to the lining of blood vessels. However, the event plays a role in the development of both atherosclerosis and rheumatoid arthritis. Activation of endothelial cells by VCAM-1 is responsible for free radical generation, namely the release of reactive oxygen species (ROS), which is quenched by vitamin E. This process reduces the oxidative burden of having an overload of free radicals. The high concentration of free radicals adversely affects the cell factor NF-κB which in turn is linked inflammatory and autoimmune diseases like arthritis. Vitamin E mitigates this adverse effect by eliminating the buildup of free radicals. It also prevents monocyte invasion into endothelial cell walls thereby reducing plaques in the arteries.

Vitamin C, Polyphenols and Prooxidants


Prooxidants are compounds that induce ROS formation. They cause cellular injury and are neutralized by antioxidants. Some polyphenols do have a prooxidant effect through the increased intracellular production of the NOX family of enzymes (NADP Oxidase). The NOX enzymes play a role in generating ROS which are also involved in stimulation of cell growth, new blood vessel formation and the elimination of effete cells. Biological oxidation produces oxidative stress and subsequently cell damage and diseases. Overproduction of ROS, nonetheless, overwhelms the defenses resulting in oxidative stress and chronic diseases. Despite its injurious effects, these compounds have been investigated for use as therapeutic agents against cancer. Prooxidant polyphenols kill cancer cells by increasing intracellular ROS formation. They also cause cell cycle arrest thereby preventing further multiplication of cancer cells.
Vitamin C (ascorbic acid) is major food prooxidant . Although vitamin C is a powerful antioxidant, does have prooxidant effect by creating free radicals. Vitamin C is a water-soluble natural antioxidant that quenches ROS. It therefore effectively reduces the risk of cancer by diminishing the influence of excessive free radicals. Vitamin C has antioxidant activity when it reduces oxidizing substances such as hydrogen peroxide. It can, however, reduce metal ions (e.g. copper, iron) which leads to the generation of free radicals: hydroxyl radical (HO.), superoxide radical (O2.-) or hydrogen peroxide (H2O2). These radicals have been reported to be able to induce cell toxicity by causing breaks in the DNA backbone. Nonetheless, in vivo studies, show that diets supplemented with ascorbic acid induced regression liposarcoma: a cancer that arises in fat cells of soft tissue.

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