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Exercise and oxidative stress/Egzersiz ve oksidatif stres.

Regular physical activity (exercise training) is an important factor in the prevention and treatment of cardiovascular disease. As littie as 30 minutes per day of moderate-intensity physical activity, including brisk walking, reduces the incidence of clinical cardiovascular events in men and women (1-4). Exercise training improves vascular endothelial function with improved nitric oxide bioavailability as a result of enhanced synthesis and reduced oxidative stress-mediated destruction (5-7).

However, acute-intense exercise does not elicit the same response as long-term exercise training. Although regular exercise training decreases oxidative stress, strenuous acute physical exercise can cause oxidative stress and subsequent damage to cellular proteins, lipids and nucleic acids as weil as changes to the glutathione system (8-12). Gul et al. (13) have found the decrease in superoxide dismutase activity in heart during the acute exercise in untrained rats.

However this was not observed by endurance training in trained rat, revealing its potential role in myocardial antioxidant defense (13). In Iong term exercise training, the acute exercise-induced increase in oxidative stress may be counter-regulated by nitric oxide-dependent vascular remodeling process leading to an increased vessel caliber and a structural normalization (14-15).

Acute muscular exercise results in an increased production of free radicals and other forms of reactive oxygen species such as superoxide and hydrogen peroxide (16-19). The antioxidant system is used to protect organism from harmful effects of free radicals. This system consists of antioxidant enzymes (catalase, glutathione peroxidase, superoxide dismutase) and non-enzymatic antioxidants (vitamin E, vitamin A, vitamin C, glutathione and uric acid). The imbalance between free radical production and antioxidant defense leads to an oxidative stress state.

In this issue of the Anatolian Journal of Cardiology, a study on the effects of treadmill exercise testing on oxidative and antioxidative parameters, and DNA damage is published (20). The authors investigated acute effects of treadmill exercise testing on total peroxide, total antioxidant capacity, oxidative stress index and DNA damage in 113 untrained subjects. They found that treadmill exercise testing increases oxidants, decreases total antioxidant capacity and vitamin C, but could not observe significant DNA damage with exercise.

Most of studies about exercise and oxidative stress were performed with high or moderate intensity exercise regimens (13,16,18). However, in this study, authors investigated effects oftreadmill exercise testing on oxidative parameters and DNA damage. Treadmill stress test is a short-term exercise testing and is widely used in subjects with suspected coronary artery disease. This aspect of the study is important.

However, there are some limitations in this study. It was carried out in subjects with typical angina or angina-like symptoms. Thirty-one subjects had positive treadmill stress testing. Although changes of oxidative and antioxidative parameters were not significantly different in subjects with positive and negative exercise test, coronary ischemia in the patients with coronary artery disease might affect levels of oxidative and antioxidative parameters. Leaf et al. (21) studied exercise-induced oxidative stress in patients during thallium stress testing. They found that patients having ischemia by exercise-thallium testing had an increase in plasma malonaldehyde levels (a marker of lipid peroxidation) with exercise, suggesting that exercise-induced oxidative stress may be related to myocardial ischemia and reperfusion (21).

Dayan et al. also studied effect of short-term intensive exercise on the some oxidative parameters (22). They applied cardiopulmonary exercise stress test to 30 healthy male subjects and could not observe any significant effect of exercise on oxidation products and vitamin E concentration. They concluded that short graded maximal exercise lasting 8-12 minutes, is not sufficient to increase the susceptibility of serum lipids to oxidation, and antioxidant capacity of most healthy subjects provides proper protection from a short exercise. Previous studies showed that, exhaustive aerobic exercise induces DNA damage (23, 24). In this study during treadmill exercise testing, authors could not observe any significant DNA damage. The effect of exercise on DNA damage appears to be related to the intensity of the exercise (25).

In conclusion, during the acute bouts of exercise even with a standard treadmill stress testing, a transient increase in vascular oxidative stress may be initiated. So, we have to be careful when prescribing the exercise to patients with cardiovascular disease such as coronary artery disease or heart failure. We have to individualize the exercise programs to patients. However, to achieve beneficial prognostic effects is still uncertain and recommendations vary between 2.5 hours of walking and exercise training equivalent to 10 km of running per week (2, 26). Further clinical studies on this subject are needed.


(1.) Hakim AA, Petrovitch H, Burchfiel CM, Ross GW, Rodriguez BL, White LR, et al. Effects of walking on mortality among nonsmoking retired men. N Eng J Med 1998; 338: 94-9.

(2.) Manson JE, Greenland P, LaCroix AZ, Stefanick ML, Mouton CP, Oberman A, et al. Walking compared with vigorous exercise for the prevention of cardiovascular events in women. N Eng J Med 2002; 347: 716-25.

(3.) Bassuk SS, Manson JF. Physical activity and the prevention of cardiovascular disease. Curr Atheroscler Rep 2003; 5: 299-307.

(4.) Walther C, Gielen S, Hambrecht R. The effect of exercise training on endothelial function in cardiovascular disease in humans. Exerc Sport Sci Rev 2004; 32: 129-34.

(5.) Rush JW, Denniss SG, Graham DA. Vascular nitric oxide and the oxidative stress: determinants of endothelial adaptations to cardiovascular disease and to physical activity. Can J Appl Physiol 2005; 30: 442-74.

(6.) Edward DG, Schofield RS, Lennon SL, Pierce HL, Nichols WW, Braith RW. Effect of exercise training on endothelial function in men with coronary artery disease. Am J Cardiol 2004; 93: 617-20.

(7.) Linke A, Adams V, Schulze PC, Erbs S, Gielen S, Fiehn E, et al. Antioxidative effects of exercise training in patients with chronic heart failure. Circulation 2005; 111: 1763-70.

(8.) Liu J, Yeo HC, Overvik-Douki E, Hagen T, Doniger S J, Chu DW, et al. Chronically and acutely exercised rats: biomarkers of oxidative stress and endogenous antioxidants. J Appl Physiol 2000; 89: 21-8.

(9.) Bloomer RJ, Goldfarb AH, Wideman L, McKenzie MJ, Consitt LA: Effects of acute aerobic and anaerobic exercise on blood markers of oxidative stress. J Strength Cond Res. 2005; 19: 276-85.

(10.) Parise G, Brose AN, Tarnopolsky MA. Resistance exercise training decreases oxidative damage to DNA and increases cytochrome oxidase activity in older adults. Exp Gerontol 2005; 40: 173-80.

(11.) Fatouros IG, Jamurtas AZ, Villiotou V, Pouliopoulou S, Fotinakis P, Taxildaris K, et al. Oxidative stress responses in older men during endurance training and detraining. Med Sci Sports Exerc 2004; 36: 2065-72.

(12.) Vincent HK, Morgan JW, Vincent KR. Obesity exacerbates oxidative stress levels after acute exercise. Med Sci Sports Exerc 2004; 36: 772-9.

(13.) Gul M, Demircan B, Taysi S, Oztasan N, Gumustekin K, Siktar E, et al. Effects of endurance training and acute exhaustive exercise on antioxidant defense mechanisms in rat heart. Comp Biochem Physiol 2006; 143: 239-45.

(14.) Green DJ, Maiorana A, O'Driscoll G, Taylor R. Effect of exercise training on endothelium-derived nitric oxide function in humans. J Physiol 2004; 561: 1-25.

(15.) Banerjee AK, Mandal A, Chanda D, Chakraborti S. Oxidant, anti-oxidant and physical exercise. Mol Cell Biochem 2003; 253: 307-12.

(16.) Finaud J, Scislowwski V, Lac G, Durand D, Vidalin H, Robert A, et al. Antioxidant status and oxidative stress in professional rugby players: evolution throughout a season. Int J Sports Med 2006; 27: 87-93.

(17.) Kojda G, Hambrecht R. Molecular mechanisms of valvular adaptations to exercise. Physical activity as an effective antioxidant therapy? Cardiovascular Research 2005; 67: 187-97.

(18.) Sureda A, Tauler P, Aguilo A, Cases N, Fuentespina E, Cordova A, et al. Relation between oxidative stress markers and antioxidant endogenous defenses during exhaustive exercise. Free Radical Research 2005; 39: 1317-24.

(19.) Galassetti PR, Nemet D, Pescatello A, Rose-Gottron C, Larson J, Cooper DM. Exercise, caloric restriction, and systemic oxidative stress. J Investig Med 2006; 54: 67-75.

(20.) Demirbag R, Yilmaz R, Guzel S, Celik H, Kocyigit A, Ozcan E. Effects of treadmill exercise test on oxidative-antioxidative parameters and DNA damage. Anadolu Kardiol Derg 2006; 2: 135-40.

(21.) Alexander LD, Mark Y, Donna G, Michael K. Exercise-induced oxidative stress in patients during Thallium Stress Testing. Am J Med Sci 1998; 315: 185-7.

(22.) Dayan A, Rotstein A, Pinchuk I, Vodovicz A, Lencovski Z, Lichtenberg D, et al. Effect of a short-term graded exhaustive exercise on the susceptibility of serum lipids to oxidation. Int J Sports Med 2005; 26: 732-8.

(23.) Davison GW, Hughes CM, Bell RA. Exercise and mononuclear cell DNA damage: the effects of antioxidant supplementation. Int J Sport Nutr Exerc Metab 2005; 15: 480-92.

(24.) Briviba K, Watzl B, Nickel K, Kulling S, Bos K, Haertel S, et al. A half-marathon and a marathon run induce oxidative DNA damage, reduce antioxidant capacity to protect DNA against damage and modify immune function in hobby runners. Redox Rep 2005; 10: 325-31.

(25.) Van Remmen H, Hamilton ML, Richardson A. Oxidative damage to DNA and aging. Exerc Sport Sci Rev 2003; 31: 149-53.

(26.) Clark AM, Hartling L, Vandermeer B, McAlister FA. Meta-analysis: secondary prevention programs for patients with coronary artery disease. Ann Intern Med 2005; 143: 659-72.

Dilek Cicek

Department of Cardiology

Medical Faculty, Mersin University

Mersin, Turkey
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Title Annotation:Editorial Comment/Editoryel Yorum
Publication:The Anatolian Journal of Cardiology (Anadolu Kardiyoloji Dergisi)
Article Type:Clinical report
Date:Jun 1, 2006
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