English

Abstract

Introduction Chronic inflammation is a prolonged pathological condition characterised by mononuclear cell infiltration, tissue destruction and fibrosis due to excess production of free radicals. Rheumatoid arthritis is systemic autoimmune disease characterised by synovial cell infiltration as well as destruction of tissues. Free radicals are defined as molecules or any chemical species having an unpaired electron in the outer orbit and are capable of independent existence. In biological systems, the most common source of free radicals is oxygen which in term reacts with nitrogen and produces nitrogen intermediates. Under certain stress conditions, Oxygen becomes much more active and forms superoxide anion radicals and hydroxyl radical (OH−). The important nitrogen species are nitric oxide and peroxynitrite anion. Nicotinamide adenine dinucleotide phosphate oxidation by Nicotinamide adenine dinucleotide phosphate oxidase is considered as the major source of Superoxide anion radicals, where the antioxidant enzyme superoxide dismutase converts Superoxide anion radicals to less toxic hydrogen peroxide. Nitric oxides are formed from L-arginine by one of the three nitric oxide synthases Free radical biology in cellular inflammation related to rheumatoid arthritis A Bala1,2*, PK Haldar1 and react with O2 and produce highly toxic Peroxynitrite. Collectively all reactive oxygen and nitrogen species are ultimately responsible for creating oxidative stress during inflammation by producing different cytotoxic cytokines through the phosphorylation of nuclear factor kappa-B (NFκB). The main aim of this review is to analyse the role of free radicals in cellular inflammation, related to rheumatoid arthritis. Conclusion DNA damage caused by reactive radicals as well as cytokines may lead to abnormal functioning of the cells. Although cellular repair systems correct most of these damages but the free radicals induced DNA lesions can be an important aetiology of inflammatory autoimmune diseases like rheumatoid arthritis. Thus it should be recommended that management of oxidative stress by antioxidant therapies in combination with modulators of cytokines and other inflammatory pathways are the therapeutic weapon to fight against rheumatoid arthritis. Introduction Inflammation is a protective defence mechanism employed by cells/ tissues against endogenous and exogenous stimuli/antigens1. The relationship between chronic inflammation and rheumatoid arthritis (RA) has already been recognised2. RA is a systemic autoimmune disorder that primarily targets the synovium of diarthrodial joints resulting in an unchecked synovial inflammation3,4 and accumulation of inflammatory cells like monocytes, macrophages and neutrophils in sinovium. In acute inflammatory processes there is a marked accumulation of polymorphonuclear neutrophills however, chronic inflammation is a prolonged pathological condition characterised by mononuclear immune cell infiltration, tissue destruction and fibrosis due to excess production of reactive oxygen and nitrogen species (ROS and RNS) as well as toxic free radicals5. Chronic inflammation exerts its cellular side effects mainly through excessive production of free radicals and depletion of antioxidant defence in the body6. The main aim of this review is to analyse the role of free radicals in cellular inflammation, related to RA. What is free radical? In the general structure of atoms and molecules, electrons are usually associated and exist in pairs, each pair moving within a defined region of space (an atomic or molecular orbital). One electron in each pair has a spin quantum number of + 1⁄2, the other − 1⁄27. Free radicals are defined as molecules or any chemical species with an unpaired electron in the outer orbit and are capable of independent existence (hence the term ‘free’)8. This unpaired electron usually produces a highly reactive free radical. In biological systems, the most common source of free radicals is oxygen which in term reacts with nitrogen and produces nitrogen intermediates and is termed as ROS and RNS9. Under certain stress conditions, Oxygen becomes much more active and forms ROS, such as superoxide anion radicals (O2), hydroxyl radical (OH−), peroxyl radical (ROO−) * Corresponding author Email: asisbala_ju@yahoo.co.in 1 Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, West Bengal, India 2 Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F Nillgunj Road, Panihati, Sodepur, Kolkata 700114, West Bengal, India