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Oxidative stress in exercising horses : fact or fiction ? Nathalie Kirschvink and Pierre Lekeux, What is oxidative stress ?Oxidative stress is defined as an imbalance between the endogenous antioxidant defence of the organism and the exogenous or endogenous pro-oxidant burden in favour of pro-oxidants. Pro-oxidants are highly reactive molecules able to induce cellular damage by oxidation of cellular components, such as lipids, proteins, nucleic acids and carbohydrates. These "reactive oxygen species" (ROS) are generated by three physiologic processes:
Antioxidants, such as vitamin A, C and E, glutathione, flavonoids, uric acid etc., are able to transform or inactivate ROS into less reactive molecules. Antioxidants are therefore essential to prevent cellular damage by pro-oxidants. How can we diagnose oxidative stress?By reacting with antioxidants or other cellular components, ROS are inactivated and can no more be detected. As ROS are highly reactive, they are very short-living molecules, which are difficult to evidence. However, their "fingerprint", that is the modification of the biological matrix the ROS reacted with, remains detectable for longer time periods. Therefore, most of the techniques attempting to diagnose oxidative stress are based on the analysis of "oxidative markers". These markers mainly include oxidation products, such as lipid peroxides, oxidised proteins or nucleic acids, or antioxidants whose concentration or activity is modified. The oxidant markers can be analysed in body fluids (blood, urine, synovial fluid, …) or tissues (liver, muscle, kidney, blood vessels,…). However, most of the analyses require sophisticated material and methods and are not yet routinely performed. How harmful is oxidative stress ?The question whether oxidative stress is harmful per se remains to be answered, but it is commonly accepted that an imbalance between the anti-oxidant and the pro-oxidant burden in favour of pro-oxidants is at least favouring the pathogenesis of numerous diseases. In fact, it is clearly established that increased amounts of ROS are released during inflammatory processes and that they contribute to upregulate and to auto-activate the inflammatory response, which can be deleterious in chronic diseases such as asthma, chronic obstructive pulmonary disease, arteriosclerosis, rheumatoid joint disease,... What do we know about oxidative stress in horses ?Disease-related oxidative stressIn equine medicine, the number of studies devoted to oxidative stress is increasing and oxidative stress is believed to play a role in several diseases. The relation between oxidative stress and lower airway disease, i.e. heaves, has been investigated. It has been demonstrated that heaves-affected horses suffer from pulmonary oxidative stress, which is correlated with lung dysfunction and airway inflammation. Furthermore, there are indices of systemic oxidative stress detectable in blood of heaves-affected horses. Other studies are indicating that exercise-induced pulmonary haemorrhage (EIPH) and exercise-induced rhabdomyolysis are favoured by pro-oxidants. Oxidative stress is also believed to play a deleterious role in muscle ischemia-reperfusion injury occurring during/after anaesthesia. The role of oxidative stress in the motor neuron disease is currently investigated. Exercise-related oxidative stressExercising horses dramatically increase their oxygen consumption in order to generate energy necessary for muscle contraction. Most of the oxygen (98 %) is reduced by the mitochondrial respiratory chain into water, but 2 % are liberated as ROS. During exercise, the release of ROS raises significantly, which implies that increased amounts of anti-oxidants are necessary to prevent oxidative stress. However, the equilibrium between pro- and anti-oxidants is depending on numerous factors, such as training, exercise intensity, nutrition, age, disease, exercise conditions (training or competition),… Some of these factors have been investigated, but it is currently not yet possible to apply this knowledge in field conditions. It has been shown that oxidative stress increases with exercise intensity and duration, that it is affected by temperature and relative air humidity and that exercise-induced oxidative stress in increased in horses suffering from heaves. Studies investigating the effect of training, over-training, nutrition, age and exercise conditions have been started recently. Exercise-induced oxidative stress is believed to contribute to poor performance, but it is not clearly established by which pathways. However, as exceeding ROS are probably favouring exercise-related diseases (EIPH, rhabdomyolysis), prevention or modulation of exercise-induced oxidative stress appears to be appropriate. How can we prevent or modulate oxidative stress ?Antioxidants are the cornerstone of the defence against oxidative stress. Endogenous antioxidants, such as glutathione, ubiquinone, antioxidant enzymes,… can be synthesized by the organism, whereas exogenous antioxidants have to be provided by food intake. Even if the importance of antioxidant deficiencies for exercise intolerance has been clearly established, the opposite that is that supplementation of antioxidants might improve performance, remains to be proven. However, some studies performed in the equine species indicate that experimental antioxidant supplementation might decrease exercise-induced oxidative stress. It further appears that antioxidant therapy must be adapted to the specific needs. In fact, overdoses of antioxidants, such as vitamin A, vitamin C or oligo-elements (copper, magnesium,…) might act as pro-oxidants and induce oxidative damage. Therefore, further studies are warranted in order to define the specific needs of antioxidants in horses. Future directionsExercise-induced and disease-related oxidative stress is currently under investigation by several research groups. Prevention and modulation of oxidative stress appears as a new medical target in equine sports medicine. Therefore, diagnostic methods applicable in field conditions need to be developed in order to assess the antioxidant status of competition horses and to define their specific need in antioxidants
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