A REVIEW OF FREE RADICALS AND RHEUMATOID ARTHRITIS
Purbajit Chetia*, Manash Pratim Pathak, Prerona Das
Deptt. of Pharmacology,
Himalayan Pharmacy Institute, Majhitar,
Rangpo, E- Sikkim(737132)
A free radical is an atom or group of atoms that contains at least one unpaired electron and can easily bond with another atom or molecule, causing a chemical reaction. Free radical is essential for body’s normal physiological functions. But when produced in excess quantities it can causes damage to the cells of the body. Human body generates pro-oxidants in the form of ROS and RNS which are effectively kept in check by the various levels of antioxidant defense. However, when it gets exposed to adverse physicochemical, environmental or pathological agents this delicately maintained balance is shifted in favor of pro-oxidants resulting in ‘oxidative stresses’. It has been implicated in the etiology of several human diseases including Rheumatoid Arthritis (RA) and in the process of ageing.At high concentrations, ROS can be important mediators of damage to cell structures, nucleic acids, lipids and proteins in case of the patients those who are suffering from RA. The hydroxyl radical is known to react with all components of the DNA molecule, damaging both the purine and pyrimidine bases and also the deoxyribose backbone. Rheumatoid arthritis is an autoimmune disease that causes chronic inflammation of the joints and tissue around the joints with infiltration of macrophages and activated T cells. The pathogenesis of this disease is linked predominantly with the formation of free radicals at the site of inflammation. The review is focusing the evidences concerning the involvement of free radicals in Rheumatoid Arthritis and their relationship to specific pathophysiological events.
Reference Id: PHARMATUTOR-ART-1336
Free radicals can be defined as molecules or molecular fragments containing one or more unpaired electrons in atomic or molecular orbitals and is capable of exciting independently 1. Generally free radicals attack the nearest stable molecule by stealing it’s electron. The attack molecule then loses its electron and becomes a free radical itself, beginning a chain reaction cascade resulting in damage to the living cells 2. Free radicals can be formed by hemolytic bond fission or by electron transfer reactions. In general such process proceed either through the absorption of radiation, redox reaction, oxidative phosphorylation in mitochondria, activation of phagocytic cells, biotransformation of exogenous and endogenous compounds in endoplasmic reticulum etc. The precursors of free radical include a variety of xenobiotics like photochemicals, pollutants, cigarette smoking, chemicals drugs, heavy metals and the constituents of many food stuff as well as endogenous compounds that can be converted to reactive radical spesis 3. Some common free radicals are such as superoxide anion radical (O2 •−), hydroxyl radical, (•OH), Peroxyl radical (HOO•),Nitric oxide (NO•) etc. The present paper concentrates on the reviewing of the evidences concerning the involvement of free radicals in Rheumatoid Arthritis and their relationship to specific pathophysiological events.
Molecular oxygen (dioxygen) which has a unique electronic configuration and is itself a radical forms the superoxide anion radical (O2 •−) by adding of one electron to dioxygen 4. The mitochondria of a cell are mainly responsible for the production of superoxide radical. The mitochondrial electron transport chain is the main source of ATP in the mammalian cell and thus is essential for life. During energy transduction, a small number of electrons “leak” to oxygen prematurely, forming the oxygen free radical superoxide, which has been implicated in the pathophysiology of a variety of diseases 5.
The hydroxyl radical, •OH, is the neutral form of the hydroxide ion. The hydroxyl radical has a high reactivity, making it a very dangerous radical with a very short in vivo half-life 6.Thus when produced in vivo •OH reacts close to its site of formation. Under stress conditions, an excess of superoxide releases “free iron” from iron-containing molecules that can participate in the Fenton reaction, generating highly reactive hydroxyl radical .Thus under stress conditions, (O2•−) facilitates •OH production from H2O2 by making Fe2+ available for the Fenton reaction7.
HOO•is the simplest peroxyl radical which is the protonated form of superoxide (O2 •−) and is usually termed either hydroperoxyl radical or perhydroxyl radical that initiates fatty acid peroxidation 8. Peroxisomes are major sites of oxygen consumption in the cell and participate in several metabolic functions that use oxygen. It maintains a delicate balance with respect to the relative concentrations or activities of the enzyme like catalase to ensure no net production of ROS. When peroxisomes are damaged and their H2O2 consuming enzymes downregulated, H2O2 releases into the cytosol which is significantly contributing to oxidative stress 9.
NO• is a small molecule that contains one unpaired electron. Itis generated in biological tissues by specific nitric oxide synthases (NOSs), which metabolise arginine to citrulline with the formation of NO• via a five electron oxidative reaction10. Nitric oxide (NO•) is an abundant reactive radical that acts as an important oxidative biological signalling molecule in a large variety of diverse physiological processes, including neurotransmission, blood pressure regulation, defence mechanisms, smooth muscle relaxation and immune regulation. In the extracellular milieu, NO• reacts with oxygen and water to form nitrate and nitrite anions. Overproduction of reactive nitrogen species is called nitrosative stress 11.This may occur when the generation of reactive nitrogen species in a system exceeds the system’s ability to neutralize and eliminate them. Nitrosative stress may lead to nitrosylation reactions that can alter the structure of proteins and so inhibit their normal function. Cells of the immune system produce both the superoxide anion and nitric oxide during the oxidative burst triggered during inflammatory processes. Under these conditions, nitric oxide and the superoxide anion may react together to produce significant amounts of a much more oxidatively active molecule, peroxynitrite anion (ONOO−), which is a potent oxidising agent that can cause DNA fragmentation and lipid oxidation 12.
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