FREE RADICALS AND ANTIOXIDANTS – CURRENT STATUS A REVIEW I

Chief Editor
DR T R RAMANUJAM M.D., C.MI.Biol (Lond)

INTRODUCTION

WHAT ARE FREE RADICALS AND ANTIOXIDANTS

INVIVO ORIGIN OF FREE RADICALS

SOURCES OF OXIDATIVE STRESS IN HUMAN PATHOPHYSIOLOGY

MAJOR TARGETS OF OXIDATIVE ACTIVITY

WHAT ARE FREE RADICALS AND ANTIOXIDANTS

Free Radicals are energetically unstable atoms or molecules capable of independent existence containing one or more unpaired electrons in their outer orbitals which are highly reactive and short lived species whose stability is achieved by removal of electrons (i.e., Oxidation of) surrounding molecules to produce an electron pair.

However, the remainder of the attacked molecule then possess an unpaired electron and has therefore become a free radical by this way may initiate a chain sequence of electron transfer (Redox reaction)

(The reaction of F.R. with non radical species)

SOURCE OF FREE RADICALS:

In aerobic cells, incomplete reductions ofO₂in the mitochodrial electron transport chain releases superoxide anion radicals in the cytosol. The superoxide readical is relaticely unreactive but may intereact with trasition metal icons such as iron, Cu to produce highly reactive and damaging hydroxylated radicals. Powerful metal binding reactions exist to prevent its participation in redox reactions. The enzyme Xanthine oxidase may also a source of superoxide formation during reperfusion of ischemic tissues.

Inflammatory cells like macrophages, neutrophils produce H₂O₂ and hypochlorous acid as a means of bacterial killing, which may damage innocent bystander cells and be responsible for much of the damage associated inflammatory processes. Certain type of drug toxicity ex. Paracetamol induced hepatotoxicity is due to the promotion of Free radical formation during their metabolism and similarly cigratte smoking induces free radical formation by virtue of its Gas phase rich in free radicals.

Superoxide anion (O₂^.-) is the most widely produced Free Radical. It is anegatively charged monoradical resulting from the monovalent reduction of molecular O₂

And essentially produced enzymatically by;

• NADPH oxidases (phagocytosis)
• Mit Cyt oxidase (cell respiration)
• Liver Cyt P₄₅₀ (oxid metabolism of Xenobiotics)
• Xanthine oxidase (ishemic reperfusion)

In the presence of protons , its dismutation leads to O₂ + H₂O₂

             2H⁺

2O₂H₂O₂ + O₂

             SOD

This reaction is highly favoured by Superoxide dismutase.

Hydroxyl radical (^. OH) is also produced in tissues and several times more reactive than O2.- and leads to easily to the formation of new free radicals. It can be formed from H₂O₂

Which in the presence of Ferrous (Fe ⁺⁺) ions leads to OH^- and ^.OH, according to Fenton reaction.

X-Fe⁺⁺ + H₂O₂X.Fe³⁺ + OH^- + ^.OH

H₂O₂which is not a free radical has nevertheless has a high oxidative capacity via this reaction. H₂O₂ is able to cross biologic membrane and to induce cellular damages by a fenton reaction, resulting in the formation of ^.OH free radical.

Peroxyl (ROO^.) and alcoxyl (RO^.) free radicals are also synthesizes essentially from polyunsaturated fatty acids either in a direct and controlled way or in an indirect and uncontrolled way. Peroxyl (ROO^.) free radicals result from the action of oxyganases (COX or LOX ie., Cycloxoygenase and Lipoxygenases) and lead to the eicosanoid pathway and in case of alcoxyl (RO^.) result from the action .OH, leading to the formation of an oxygen free radical ROO^. This constitutes the initial phase of Lipid peroxidation.