Oxidative stress in equine medicine - Current knowledge

Abstract

Since Davies et al. have demonstrated in 1982 that physical exercise is generating free radicals, their role and effects on the organism have become of increasing interest. Free radicals are molecules that have an unpaired electron in their outer orbit, which increases their reactivity with other molecules. Reactive oxidant species (ROS) can be defined as oxygencontaining molecules that are more reactive than the triplet oxygen molecule present in air (Noguchi and Niki, 1999). At present, ROS are considered to be important messengers acting in living organisms, which are constantly produced by numerous metabolic reactions. The generation of ROS is increased by phagocytes during inflammatory processes as well as by physical exercise via the upregulation of the mitochondrial metabolism. Some enzymes, such as oxidases, are also able to generate ROS (Cheeseman and Slater, 1993; Ji, 1995). The most important role of ROS is the defence against invading microorganisms and the so-called “redox-regulation” of gene expression (MacPherson et al., 2001; Stamler & Meisner, 2001). The generation of ROS is significantly increased in inflammatory conditions during the “oxidative burst” of neutrophils and macrophages (Rahman et al., 1996). The activation of pro-oxidative enzymes, such as the NADPH-oxidase (nicotinamide adenine dinucleotide phosphate oxidase) and the myeloperoxidase (MPO) in presence of transition metals such as copper or iron, allows the generation of important amounts of ROS that are released by inflammatory cells. These oxidants play an important role in the inactivation and destruction of microorganisms by inducing peroxidation and destabilization of their lipid membranes, oxidation and inactivation of their proteins acting as receptors or enzymes and oxidation of their nuclear material (Kowaltowski and Vercesi, 1999; Kobayashi et al., 2001). Beside this important role for immunity, the ROS are also cellular messengers. The redox-regulation of intracellular signal transduction is based on the oxidation and reduction of messenger proteins, thereby activating or inactivating intracellular pathways. Especially the expression of inflammatory genes is depending on oxidation-reduction reactions, which confers to the ROS the role of pro-inflammatory stimuli (Hensley et al., 2000). Nathalie Kirschvink und P. Lekeux