At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

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Free Radicals in the Physiological Control of Cell Function

The first suggestion that physical exercise results in free radical-mediated damage to tissues appeared in 1978, and the past three decades have resulted in a large growth of knowledge regarding exercise and oxidative stress. Although the sources of oxidant production during exercise continue to be debated, it is now well established that both resting and contracting skeletal muscles produce reactive oxygen species and reactive nitrogen species. Importantly, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Furthermore, oxidants can modulate a number of cell signaling pathways and regulate the expression of multiple genes in eukaryotic cells. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, DNA repair proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species promote contractile dysfunction resulting in muscle weakness and fatigue. Ongoing research continues to probe the mechanisms by which oxidants influence skeletal muscle contractile properties and to explore interventions capable of protecting muscle from oxidant-mediated dysfunction.

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Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production

http://www.cibr.es/ka/apps/cibr/docs/15_07_2003_SUPLEMENTOS.pdf

Oxidative stress, exercise, and antioxidant supplementation.

Moderate exercise is an antioxidant: upregulation of antioxidant genes by training.

Strenuous exercise increases oxygen consumption and causes disturbance of intracellular pro-oxidant-antioxidant homeostasis. The mitochondrial electron transport chain, polymorphoneutrophil, and xanthine oxidase have been identified as major sources of intracellular free radical generation during exercise. Reactive oxygen species pose a serious threat to the cellular antioxidant defense system, such as diminished reserve of antioxidant vitamins and glutathione, and increased tissue susceptibility to oxidative damage. However, enzymatic and nonenzymatic antioxidants have demonstrated great adaptation to acute and chronic exercise. The delicate balance between pro-oxidants and antioxidants suggests that supplementation of antioxidants may be desirable for physically active individuals under certain physiological conditions by providing a larger protective margin.

Antioxidants and oxidative stress in exercise

We have studied the effect of exhaustive concentric physical exercise on glutathione redox status and the possible relationship between blood glutathione oxidation and blood lactate and pyruvate levels. Levels of oxidized glutathione (GSSG) in blood increase after exhaustive concentric physical exercise in trained humans. GSSG levels were 72% higher immediately after exercise than at rest. They returned to normal values 1 h after exercise. Blood reduced glutathione (GSH) levels did not change significantly after the exercise. We have found a linear relationship between GSSG-to-GSH and lactate-to-pyruvate ratios in human blood before, during, and after exhaustive exercise. In rats, physical exercise also caused an increase in blood GSSG levels that were 200% higher after physical exercise than at rest. GSH levels did not change significantly. Thus, both in rats and humans, exhaustive physical exercise causes a change in glutathione redox status in blood. We have also found that antioxidant administration, i.e., oral vitamin C, N-acetyl-L-cysteine, or glutathione, is effective in preventing oxidation of the blood glutathione pool after physical exercise in rats.

Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration.

L-cysteine and glutathione metabolism are impaired in premature infants due to cystathionase deficiency.

The activity of liver cystathionase (EC 4.4.1.1) was decreased after 3 d of stress induced by surgery. The rate of l-cysteine synthesis from l-methionine was significantly higher in isolated hepatocytes from controls than in hepatocytes from rats suffering from surgical stress. The half-life of l-[2(n)-3H]methionine was significantly higher in rats submitted to surgical stress than in controls. Plasma l-methionine: l-cystine ratio was higher in stressed rats than in controls. l-cystine uptake was significantly increased in the surgically-stressed rats when compared with the controls. All these facts are consistent with the hypothesis that the observed inhibition of cystathionase is physiologically important and thatl-cysteine might be considered as an essential amino acid in cases of surgical stress.

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Impairment of cysteine synthesis from methionine in rats exposed to surgical stress.

Eye lenses from young rats or mice synthesize GSH from methionine or N-acetylcysteine. However, lenses from old animals do not synthesize GSH from methionine. This is due to the absence of cystathionase activity in old lenses. GSH monoethyl ester, but not free GSH, increases GSH content and protects the lens against experimental oxidative stress. The importance of these results in the prevention of cataractogenesis is discussed.

Esperanza Gasco

Papers

Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration.

L-cysteine and glutathione metabolism are impaired in premature infants due to cystathionase deficiency.

Impairment of cysteine synthesis from methionine in rats exposed to surgical stress.

Age-related changes in glutathione synthesis in the eye lens.

Effect of aging on metabolic zonation in rat liver: acinar distribution of GSH metabolism.