Antioxidant Drugs

Chapter 40 Antioxidant Drugs


Oxidative Stress

Oxidative stress is an imbalance between prooxidant compounds and antioxidant defenses.1,2 Another term used to describe this summation of pro- and antioxidant molecules is the redox state.

Free Radicals

A free radical is any molecular species capable of independent existence and containing one or more unpaired electrons.1,2 Examples include the hydrogen radical (H), the superoxide free radical (O2•–), and the hydroxyl (OH) and peroxyl radicals (RO2). Metabolic processes taking place within the liver constitute a major source of free radical production. The superoxide free radical, for example, is produced by hepatic oxidative reactions and by “uncoupling” of the cytochrome P450 enzyme system. Free radicals are formed during hepatic metabolism of endogenous substances or xenobiotics such as acetaminophen.5

Reactive Oxygen Species

The term reactive oxygen species (ROS) is used to describe free radicals containing oxygen.1,2 These are molecules that are formed by the reduction of oxygen and encompass both free radicals and nonfree radicals such as hydrogen peroxide (H2O2), hypochlorous acid (HOCl), and peroxynitrite (ONOO, which is also a reactive nitrogen species). ROS are produced under normal circumstances during normal mitochondrial respiration, and during disease processes such as inflammation, necrosis, and ischemia.


Drug Classifications and Mechanisms of Action

Antioxidant defenses consist of both enzymatic and nonenzymatic processes.3 Antioxidant enzymes include superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. These antioxidant enzymes catalyze chemical reactions that utilize ROS. The end-product of their reactions is often a much less harmful compound such as water, or a metabolite that is subject to further antioxidant reactions, such as hydrogen peroxide.

Sulfur-containing glutathione is the most important of the nonenzymatic antioxidants. Thiols exert their antioxidant action through oxidation of the sulfhydryl bond of cysteine. In this way, they scavenge free radical unpaired electrons. The inhibition of lipid peroxidation by α-tocopherol (vitamin E) is another example of a scavenging antioxidant property. These antioxidants are replaceable substrates because they can be returned to their reduced form through simple chemical reactions.

Enzymatic and nonenzymatic antioxidant defenses often work synergistically. For example, after the superoxide dismutase enzyme generates hydrogen peroxide from the superoxide anion, the glutathione peroxidase enzyme converts hydrogen peroxide to water by oxidizing GSH to the disulfide form GSSG. The glutathione reductase enzyme completes the process by returning GSSG to GSH:

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Jul 10, 2016 | Posted by in INTERNAL MEDICINE | Comments Off on Antioxidant Drugs

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