Lymphocyte distribution in mouse submandibular lymph nodes in response to acute treadmill exercise

The submandibular lymph nodes (LN), part of the nasal-associated lymphoid tissue (NALT), are involved in local immune responses in the eye, upper respiratory tract (URT), and oral mucosa. Although athletes have been reported to be at increased risk for URT and ocular infections, little is known about the impact of exercise on LN included in the NALT. The purpose of this study was to examine the impact of intense acute exercise on submandibular lymphocyte distribution. Female C57BL/6 mice were randomly assigned to a nonexercised control condition or a single session of treadmill exercise (32 m.min-1, 8 degrees grade for 90 min) and sacrificed immediately, 2, and 24 h after exercise. Running resulted in a significant increase in plasma corticosterone immediately following exercise compared with other times (p < 0.001). Percentages and total numbers of CD3+ and CD4+CD8- T lymphocytes in submandibular LN were significantly lower 24 h after exercise compared with controls. The percentage of pan-NK and CD19+ B cells increased immediately and 24 h after exercise, respectively, but the total numbers were not affected. The results suggest that decreased percentages and absolute numbers of T cells in submandibular LN following a single session of intense exercise may be partially mediated by increased corticosterone concentrations and may have consequences for ocular health among athletes.     

N-Acetyl-L-cysteine prevents exercise-induced intestinal lymphocyte apoptosis by maintaining intracellular glutathione levels and reducing mitochondrial membrane depolarization

Intense exercise leads to post-exercise lymphocytopenia and immunosuppression, possibly by triggering lymphocyte apoptosis. To test the role of oxidative stress on exercise-induced lymphocyte apoptosis, we administered the antioxidant N-acetyl--cysteine (NAC) and measured apoptosis in intestinal lymphocytes (IL) from exhaustively exercised animals. Eighty-seven female C57BL/6 mice were randomly assigned to receive NAC (1 g/kg) or saline 30 min prior to treadmill exercise for 90 min at 2degrees slope (30 min at 22 m min(-1), 30 min at 25 m min(-1), and 30 min at 28 m min(-1)) and sacrificed immediately (Imm) or 24 hours (24 h) after cessation of exercise. Control mice (nonexercised) were exposed to treadmill noise and vibration without running. Exercise increased IL phosphatidylserine externalization (p<0.001), mitochondrial membrane depolarization (p<0.05), and decreased intracellular glutathione concentrations (p<0.05) immediately following exercise in saline relative to nonexercised mice. At 24 h post-exercise, saline injected mice had fewer total (p<0.001) and CD3+ (p<0.005) IL compared to nonexercised animals. NAC injection in mice maintained intracellular glutathione levels, prevented phosphatidylserine externalization, mitochondrial membrane depolarization, and loss of IL immediately and 24 h after exercise. These data suggest that lymphocyte apoptosis precedes post-exercise lymphocytopenia and may be due to oxidative stress.     

Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise.

Exhaustive exercise is associated with an increase in circulating glucocorticoids (GCs), lymphocyte apoptosis, and a reduction in intestinal lymphocyte number. The present study examined the role of GCs on the numerical changes seen in intestinal lymphocytes after exercise. Female C57BL/6 mice were bilaterally adrenalectomized (ADX; n = 18) or given sham surgery (Sham; n = 18) and assigned to one of three exercise conditions: treadmill running (28 m/min, 90 min, 2 degrees slope) and killed immediately or after 24 h recovery, or not exercised and killed immediately after 90-min exposure to the treadmill environment. Lymphocytes were isolated from the intestines with CD45(+) cells collected by positive selection using magnetic bead separation columns, and lymphocyte subpopulations were analyzed by flow cytometry for CD45(+), CD3alphabeta(+), CD3gammadelta(+), CD8beta(+), CD8alpha(+), CD4(+), and NK(+) phenotypic markers. ADX mice had significantly more intestinal CD45(+) leukocytes (P < 0.05) and CD3alphabeta(+) (P < 0.05), CD3gammadelta(+) (P < 0.01), CD8alpha(+) (P < 0.001), and NK(+) (P < 0.05) intestinal lymphocytes than Sham mice. There was a significant effect of exercise condition on total intestinal CD45(+) leukocytes (P < 0.01) and CD3alphabeta(+) (P < 0.05), CD8alpha(+) (P < 0.001), and CD4(+) (P < 0.05) intestinal lymphocytes, with fewer cells at 24 h postexercise compared with the other treatment conditions. There were no surgical x exercise interaction effects on the CD3 and CD8 phenotype numbers. Plasma corticosterone was virtually nil in ADX mice regardless of exercise condition but was significantly elevated in Sham mice immediately postexercise (P < 0.001). The data indicate that ADX does not prevent the loss of lymphocytes from the intestinal mucosa 24 h after strenuous exercise and GCs are not directly causal in the leukopenia of exercise.     

Mitogenic response of T-lymphocytes to exercise training and stress

The impact of exercise training and stress on the immune response was examined by measuring the mitogenic response of spleen lymphocytes to the T-cell mitogen concanavalin A (Con-A). Male Sprague-Dawley rats were divided into four groups: sedentary controls (n = 11), handled controls (n = 12), treadmill runners (n = 10), and voluntary runners (n = 11) housed in running wheels. The treadmill group ran at 22 m/min (0.8 mph) for 45 min, 5 days/wk for 8 wk. After the training period, spleen lymphocytes isolated from each rat were incubated with Con-A for 54 h, pulsed with radiolabeled thymidine for 18 h, and counted for tritium activity. Counts per minute per group (means +/- SE) were as follows: sedentary, 6,839 +/- 1,461; handled, 8,959 +/- 1,576; voluntary runners, 13,126 +/- 2,069; and treadmill runners, 18,950 +/- 5,975. One-way analysis of variance and Tukey's highly significant difference test found the counts per minute of the treadmill runners to be significantly different from the counts per minute of the sedentary animals. These results indicate that the responsiveness of spleen lymphocytes to Con-A increases as the level of stress and exercise increases.     

Splenic immune responses following treadmill exercise in mice

The in vitro proliferation response to lipopolysaccharide and pokeweek mitogen by splenic lymphocytes and the effect on the total splenic lymphocyte number were examined in C57BL/6J mice following an 8-week treadmill training program (30 m/min, 8 degrees slope, 30 min/day, 5 times/week) and after a single bout of exhaustive exercise (50% stepwise increases in final running speed for 10-min intervals). Plasma corticosterone levels were also measured to evaluate whether changes in adrenocortical activation were associated with exercise-induced immunomodulation. In comparison to sedentary controls, trained mice had an increase of 35% in succinate dehydrogenase activity per unit of protein in the quadriceps femoris muscle. Trained mice showed an increase in splenic lymphocyte proliferation to both mitogens which was evident 72 h after completion of the final training session, relative to sedentary controls. Immediately following exercise, however, lymphocyte proliferative responses were depressed compared with the training and the control values. The exercise regimen resulted in a reduction in total number of mononuclear cells per spleen. Changes in plasma corticosterone levels after exercise were not clearly associated with immunodepression or immunoenhancement of splenic lymphocyte mitogenesis. Taken together, the data suggest that moderate endurance training augments splenic B lymphocyte mitogenesis and further, that the immediate effects of exercise on splenic immune function vary with the duration and intensity of the work.     

Inhibitory effects of voluntary wheel exercise on apoptosis in splenic lymphocyte subsets of C57BL/6 mice.

Two-month-old mice were placed in cages with (Ex) or without exercise running wheels with free access to the wheel 24 h/day for 10 mo. An equal amount of food for both groups was provided daily. Ex mice ran an average of 33.67 km/wk initially, and exercise decreased gradually with age. Ex mice had gained an average of 43.5% less body weight at the end of the experiment. Although serum lipid peroxides were not altered by exercise, superoxide dismutase and glutathione peroxidase activities in serum were significantly increased. Flow cytometric analysis of spleen cells revealed an increased percentage of CD8+ T cells and a decreased percentage of CD19+ B cells in Ex mice (P < 0.05). Exercise decreased apoptosis in total splenocytes and CD4+ cells incubated with medium alone or with H(2)O(2), dexamethasone, tumor necrosis factor-alpha (TNF-alpha), or anti-CD3 monoclonal antibody (P < 0.05) and CD8+ cells with medium alone or with TNF-alpha (P < 0.05). Even though exercise did not alter the intracellular cytokines (TNF-alpha and interleukin-2) or Fas ligand, it did significantly lower interferon-gamma in CD4+ and CD8+ cells (P < 0.05). In summary, voluntary wheel exercise appears to decrease H(2)O(2)-induced apoptosis in immune cells as well as decrease interferon-gamma production.     

Skeletal muscle lipid peroxidation in exercised and food-restricted rats during aging

The effects of chronic endurance exercise and food restriction on nonenzymatic lipid peroxidation (LP) of gastrocnemius muscle during aging were studied in male, Fischer 344 rats. One set of rats aged 6 and 18 mo were assigned to an exercise group (treadmill running) or an age-matched sedentary control group. After 6 mo (at the ages of 12 and 24 mo), LP and levels of alpha-tocopherol and its oxidized form, alpha-tocopheryl quinone, were measured. The extent of LP was determined in homogenates by measuring the content of thiobarbituric acid-reactive substances. After homogenization, the muscles were immediately evaluated for basal LP and also incubated in the presence of oxidant stressors for 2 h to assess antioxidant capacity (AOC) and for 24 h to estimate total peroxidizable lipid (TPL). Basal LP was not affected by age or exercise. AOC was not affected by exercise at either age. However aging significantly decreased AOC and increased alpha-tocopheryl quinone in both sedentary and exercised groups. TPL was not affected by age, but was increased by exercise training (P less than 0.05). Another set of rats was divided into the following three groups at 3 mo of age: sedentary, fed ad libitum (S); sedentary, caloric restricted by alternate day feeding (R); and exercised by forced treadmill running (E). Two years later, when the rats were 27 mo of age, the extent of LP was assessed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of exercise on weight loss and monocytes in obese mice

Obesity causes innate immune dysfunction, contributing to increased disease risk. Weight loss from a combination of caloric restriction and exercise is the most effective treatment of obesity. We compared forced and voluntary exercise as weight-loss treatments in diet-induced obese (DIO) mice and assessed the effects of weight loss on monocyte concentration and cell-surface expression of Toll-like receptor (TLR) 2, TLR4, CD80, and CD86. DIO CD1 male mice were allocated randomly to 1 of 3 groups (n = 6 per group): voluntary wheel running (VEX); forced treadmill running (FEX); and sedentary (S). A fourth (control) group (CN, n = 6) of nonDIO mice was included also. During the 8-wk weight-loss treatment, all 4 groups consumed a low-fat (10% fat) diet. Nonlethal saphenous vein blood samples collected at baseline, week 4, and week 8 were analyzed by flow cytometry to assess monocyte concentration and functional receptor expression. The VEX and FEX groups lost significantly more body weight (36% and 27%, respectively) over the 8 wk of treatment than did other groups. VEX mice ran 4.4 times more than did FEX animals. VEX mice had higher monocyte concentrations (48% and 58%, respectively) than did the CN and FEX groups. Compared with baseline, week 8 cell-surface expression of TLR2 (22%), TLR4 (33%), and CD86 (18%) was increased in VEX mice. At week 4, CD80 expression was 42% greater for VEX than S mice. The present study confirms that short-term exercise and low-fat diet consumption cause significant weight loss and altered immune profiles.     

Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of oxidative CPT I modification

Intracellular redox balance may affect nutrient metabolism in skeletal muscle. Astaxanthin, a carotenoid contained in various natural foods, exerts high antioxidative capacity in the skeletal muscles. The present study investigated the effect of astaxanthin on muscle lipid metabolism in exercise. ICR mice (8 weeks old) were divided into four different groups: sedentary, sedentary treated with astaxanthin, running exercise, and exercise treated with astaxanthin. After 4 weeks of treatment, exercise groups performed treadmill running. Astaxanthin increased fat utilization during exercise compared with mice on a normal diet with prolongation of the running time to exhaustion. Colocalization of fatty acid translocase with carnitine palmitoyltransferase I (CPT I) in skeletal muscle was increased by astaxanthin. We also found that hexanoyl-lysine modification of CPT I was increased by exercise, while astaxanthin prevented this increase. In additional experiment, we found that astaxanthin treatment accelerated the decrease of body fat accumulation with exercise training. Our results suggested that astaxanthin promoted lipid metabolism rather than glucose utilization during exercise via CPT I activation, which led to improvement of endurance and efficient reduction of adipose tissue with training.     

High bone mass gained by exercise in growing male mice is increased by subsequent reduced exercise.

Exercise-induced bone gains are lost if exercise ceases. Therefore, continued exercise at a reduced frequency or intensity may be required to maintain these benefits. In this study, we evaluated whether 4 wk of reduced exercise after 4 wk of running exercise in growing male mice results in the maintenance of high bone mass. Five-week-old mice were divided into the following groups: 1) baseline control; 2) 4-wk control; 3) 4-wk exercise; 4) 8-wk control; 5) 4-wk exercise followed by 4-wk cessation of training; and 6) 4-wk exercise followed by reduced exercise at half the frequency. The regimen consisted of exercise 6 days/wk, and the reduced exercise regimen consisted of running 3 days/wk on a treadmill for 30 min/day, at 12 m/min on a 10 degrees uphill slope. Running exercise significantly increased bone mineral density of the femur, periosteal mineral apposition rate, bone formation rate, percent labeled perimeter at the midfemur, and osteogenic activity of bone marrow cells. However, these parameters declined to the age-matched sedentary control after cessation of training. In contrast, the reduced exercise group had significantly higher mineral apposition rate compared with those of the sedentary control and cessation of training groups. Furthermore, bone mineral density for the reduced exercise group was significantly higher than those for the other groups. These results suggest that the high bone formation gained through exercise can be maintained, and bone mass was further increased by subsequent exercise even if the exercise frequency is reduced.     

Antioxidant enzyme levels in intestinal and renal tissues after a 60-minute exercise in untrained mice.

The present study was designed to determine the effects of exercise on the antioxidant enzymatic system and lipid peroxidation in small intestine and kidney, during the post-exercise period in untrained mice. Two days after the last adaptation running exercise, animals were ran on the treadmill for 60 min at 18 m/min. 5 degrees slope. After the acute exercise the animals were killed by cervical dislocation, immediately (0 h), 3 hours (3 h) and 24 hours (24 h) after the exercise. Control animals were killed without running exercise. Their proximal small intestinal and renal tissues were quickly removed. Changes in the concentration of thiobarbituric acid reactive substance (TBARS), as an index of lipid peroxidation, in intestine and kidney were studied in mice after the running exercise and in unexercised control group. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were determined in these tissues. Tissue SOD, GPx activities and TBARS level were not increase by the exercise in kidney. Intestinal SOD activity decreased after exercise (0 h and 3 h respectively, p<0.05, p<0.01) and retumed to control levels. Intestinal GPx activity increased after exercise (0 h, p<0.05) and returned to control levels. There was no significant difference among groups in intestinal tissue TBARS levels. These findings could suggest that submaximal exercise may not cause oxidative stress in proximal small intestinal tissue and kidney.     

Effects of endurance training and acute exhaustive exercise on antioxidant defense mechanisms in rat heart

We investigated whether 8-week treadmill training strengthens antioxidant enzymes and decreases lipid peroxidation in rat heart. The effects of acute exhaustive exercise were also investigated. Male rats (Rattus norvegicus, Sprague-Dawley strain) were divided into trained and untrained groups. Both groups were further divided equally into two groups where the rats were studied at rest and immediately after exhaustive exercise. Endurance training consisted of treadmill running 1.5 h day(-1), 5 days week(-1) for 8 weeks. For acute exhaustive exercise, graded treadmill running was conducted. Malondialdehyde level in heart tissue was not affected by acute exhaustive exercise in untrained and trained rats. The activities of glutathione peroxidase and glutathione reductase enzymes decreased by both acute exercise and training. Glutathione S-transferase and catalase activities were not affected. Total and non-enzymatic superoxide scavenger activities were not affected either. Superoxide dismutase activity decreased by acute exercise in untrained rats; however, this decrease was not observed in trained rats. Our results suggested that rat heart has sufficient antioxidant enzyme capacity to cope with exercise-induced oxidative stress, and adaptive changes in antioxidant enzymes due to endurance training are limited.     

Regular exercise prevents high-sucrose diet-induced fatty liver via improvement of hepatic lipid metabolism

Fatty liver is known as the initial stage in nonalcoholic fatty liver disease. Epidemiological studies have shown that regular exercise prevents accumulation of hepatic lipids, although the underlying mechanism is unclear. The purpose of this study was to investigate the effect of exercise on fatty liver associated with hepatic lipid metabolism. KK/Ta mice (6 weeks old) were divided into sedentary and exercise groups and compared with sedentary Balb/c mice. All the mice were fed a high-sucrose diet for 12 weeks. The KK/Ta mice in the exercise group performed a treadmill running exercise at 20 m/min for 30 min (3 times per week). Twelve weeks of regular exercise suppressed the accumulation of lipid in the liver, along with reduction in the level of lipid in the plasma. The levels of carnitine palmitoyl transferase II, acyl-coenzyme A dehydrogenase, and trifunctional enzyme, which are rate-limiting enzymes in fatty acid oxidation in the liver, were elevated by exercise. In addition, the expression of fatty acid synthase, a key lipogenetic enzyme, was reduced by exercise. Furthermore, regular exercise decreased the expression of heat shock protein 47, a marker of hepatic fibrosis, in the liver. Our results suggest that regular exercise prevents fatty liver via improvement of hepatic lipid metabolism.     

Sex differences in physiological cardiac hypertrophy are associated with exercise-mediated changes in energy substrate availability

Exercise-induced cardiac hypertrophy has been recently identified to be regulated in a sex-specific manner. In parallel, women exhibit enhanced exercise-mediated lipolysis compared with men, which might be linked to cardiac responses. The aim of the present study was to assess if previously reported sex-dependent differences in the cardiac hypertrophic response during exercise are associated with differences in cardiac energy substrate availability/utilization. Female and male C57BL/6J mice were challenged with active treadmill running for 1.5 h/day (0.25 m/s) over 4 wk. Mice underwent cardiac and metabolic phenotyping including echocardiography, small-animal PET, peri-exercise indirect calorimetry, and analysis of adipose tissue (AT) lipolysis and cardiac gene expression. Female mice exhibited increased cardiac hypertrophic responses to exercise compared with male mice, measured by echocardiography [percent increase in left ventricular mass (LVM): female: 22.2 ± 0.8%, male: 9.0 ± 0.2%; P < 0.05]. This was associated with increased plasma free fatty acid (FFA) levels and augmented AT lipolysis in female mice after training, whereas FFA levels from male mice decreased. The respiratory quotient during exercise was significantly lower in female mice indicative for preferential utilization of fatty acids. In parallel, myocardial glucose uptake was reduced in female mice after exercise, analyzed by PET {injection dose (ID)/LVM [%ID/g]: 36.8 ± 3.5 female sedentary vs. 28.3 ± 4.3 female training; P < 0.05}, whereas cardiac glucose uptake was unaltered after exercise in male counterparts. Cardiac genes involved in fatty acid uptake/oxidation in females were increased compared with male mice. Collectively, our data demonstrate that sex differences in exercise-induced cardiac hypertrophy are associated with changes in cardiac substrate availability and utilization.     

Effect of exercise and calorie restriction on biomarkers of aging in mice

Unlike calorie restriction, exercise fails to extend maximum life span, but the mechanisms that explain this disparate effect are unknown. We used a 24-wk protocol of treadmill running, weight matching, and pair feeding to compare the effects of exercise and calorie restriction on biomarkers related to aging. This study consisted of young controls, an ad libitum-fed sedentary group, two groups that were weight matched by exercise or 9% calorie restriction, and two groups that were weight matched by 9% calorie restriction + exercise or 18% calorie restriction. After 24 wk, ad libitum-fed sedentary mice were the heaviest and fattest. When weight-matched groups were compared, mice that exercised were leaner than calorie-restricted mice. Ad libitum-fed exercise mice tended to have lower serum IGF-1 than fully-fed controls, but no difference in fasting insulin. Mice that underwent 9% calorie restriction or 9% calorie restriction + exercise, had lower insulin levels; the lowest concentrations of serum insulin and IGF-1 were observed in 18% calorie-restricted mice. Exercise resulted in elevated levels of tissue heat shock proteins, but did not accelerate the accumulation of oxidative damage. Thus, failure of exercise to slow aging in previous studies is not likely the result of increased accrual of oxidative damage and may instead be due to an inability to fully mimic the hormonal and/or metabolic response to calorie restriction.     

Interaction of regular exercise and chronic nitroglycerin treatment on blood pressure and rat aortic antioxidants

Many cardiac patients undergo exercise conditioning with or without medication. Therefore, we investigated the interaction of exercise training and chronic nitroglycerin treatment on blood pressure (BP), aortic nitric oxide (NO), oxidants and antioxidants in rats. Fisher 344 rats were divided into four groups and treated as follows: (1) sedentary control, (2) exercise training (ET) for 8 weeks, (3) nitroglycerin (15 mg/kg, s.c. for 8 weeks) and (4) ET+nitroglycerin. BP was monitored with tail-cuff method. The animals were sacrificed 24 h after the last treatments and thoracic aorta was isolated and analyzed. Exercise training on treadmill for 8 weeks significantly increased respiratory exchange ratio (RER), aortic NO levels, and endothelial nitric oxide synthase (eNOS) protein expression. Training significantly enhanced aortic glutathione (GSH), reduced to oxidized glutathione (GSH/GSSG) ratio, copper/zinc-superoxide dismutase (CuZn-SOD), Mn-SOD, catalase (CAT), glutathione peroxidase (GSH-Px) glutathione disulfide reductase (GR) activities and protein expressions. Training significantly depleted aortic malondialdehyde (MDA) and protein carbonyls without change in BP. Nitroglycerin administration for 8 weeks significantly increased aortic NO levels and eNOS protein expression. Nitroglycerin significantly enhanced aortic Mn-SOD, CAT, GR and glutathione-S-transferase (GST) activities and protein expressions with decreased MDA levels, protein carbonyls and BP. Interaction of training and nitroglycerin treatment significantly increased aortic NO levels, eNOS protein expression, GSH/GSSG ratio, antioxidant enzymes and normalized BP. The data suggest that the interaction of training and nitroglycerin maintained BP by up-regulating the aortic NO and antioxidants and reducing the oxidative stress in rats.     

Effects of exercise training on brain opioid peptides and serum LH in female rats

In order to investigate the effects of long-term exercise training on brain endorphin systems, and the latter's possible effects on the hypothalamic-pituitary-gonadal axis, female Wistar rats were subjected to daily treadmill running. A sedentary control group was also employed. After 8 weeks of training, and just prior to sacrifice, one-half of each group received a final fatiguing bout of exercise. Thus the final four groups consisted of a trained-fatigued (TF), trained-nonfatigued (TN), control-fatigued (CF), and control-nonfatigued (CN) group. Regional brain levels of beta-endorphin (beta E), methionine enkephalin and leucine enkephalin (LE) were assayed with independent RIAs from the nucleus accumbens, cortex, caudate-putamen, septum, amygdala, anterior and posterior hypothalamus, substantia nigra and ventral tegmentum. Diestrus serum levels of luteinizing hormone (LH), follicle stimulating hormone and prolactin (PRL) were also determined. Fatiguing resulted in a decrease in serum LH levels as well as an increase in beta E content in the nucleus accumbens, and LE content in the ventral tegmentum. Finally, TF animals exhibited less LE in the amygdala than the TN rats. Taken together, these changes in brain endorphins may indicate an acute, fatigue-running modulation of the hypothalamic-pituitary-gonadal axis.     

Decreased intestinal polyp multiplicity is related to exercise mode and gender in ApcMin/+ mice.

Moderate-intensity treadmill running can alter male Apc(Min/+) mouse polyp formation. This purpose of this study was to examine whether exercise mode differentially affects Apc(Min/+) mouse intestinal polyp development in male and female mice. Male and female Apc(Min/+) mice were randomly assigned to control, treadmill (18 m/min; 60 min/day; 6 days/wk), or voluntary wheel running (24-h access) groups. Nine weeks of training decreased total intestinal polyps by 29% in male treadmill runners (66 +/- 9; P = 0.038) compared with male controls (93 +/- 7). The number of large polyps (>/=1-mm diameter) were also reduced by 38% in male treadmill runners (49 +/- 6; P = 0.005) compared with male controls (79 +/- 6). Treadmill running in female Apc(Min/+) mice and wheel running in both genders did not affect polyp number or size. Spleen weight decreased in male treadmill runners (91 +/- 9 mg; P = 0.011) and wheel runners (75 +/- 6 mg; P = 0.004) compared with controls (141 +/- 13 mg). Plasma IL-6 was reduced by 96% in male treadmill runners (1.2 +/- 0.6 pg/ml) and 78% in male wheel runners (6.6 +/- 3.3 pg/ml) compared with control mice (27.9 +/- 2.8 pg/ml; P < 0.05). Female mice responded similarly with an 86% decrease in plasma IL-6 with treadmill running (3.2 +/- 1.2 pg/ml) and 90% decrease with wheel running (2.9 +/- 2.0 pg/ml) compared with control mice (21.1 +/- 5.3 pg/ml; P < 0.05). The crypt depth-to-villus height ratio in the intestine, an indirect marker of intestinal inflammation, decreased by 21 (P = 0.024) and 24% (P = 0.029), respectively, in male and female treadmill runners but not wheel runners. Physical activity-induced attenuation of intestinal polyp number and size is dependent on exercise mode and differs between genders. The modulation of systemic and intestinal inflammation may also depend on exercise mode.     

Assessment of oxidative stress in lymphocytes with exercise

This study investigated whether changes in the cellular composition of blood during exercise could partly account for observations of exercise-induced changes in lymphocyte oxidative stress markers. Markers of oxidative stress were assessed before and after 60 min of intense treadmill running. Samples were collected from 16 men (means ± SD: age 33 ± 13 yr; body mass index 23.8 ± 2.5 kg/m(2); maximal oxygen uptake 59.7 ± 5.2 ml·kg(-1)·min(-1)). Peripheral blood lymphocytes were assayed for protein carbonyl concentration, and plasma was assessed for lipid peroxides and antioxidant capacity. In a separate study, intracellular thiol concentration was determined in lymphocyte subsets from eight characteristically similar men by flow cytometry, of which T-cell memory populations were further identified on the basis of CD27, CD28, and CD45RA expression. Total lymphocyte protein carbonyls were transiently increased with exercise and returned to baseline within 15 min (P < 0.001). This change was accompanied by an increase in plasma lipid peroxides (P < 0.05) and total antioxidant capacity (P < 0.001). Correlation analyses showed that lymphocyte protein carbonyl content was not related to changes in the cellular composition of peripheral blood during exercise. Natural killer cells (CD3(-)CD56(+)) and late-differentiated/effector memory cells (CD4(+)/CD8(+)CD27(-)CD28(-)/CD45RA(+)), which mobilized most with exercise, showed high intracellular thiol content (P < 0.001). High thiol content suggests a lower oxidative load carried by these lymphocytes. Thus vigorous exercise resulted in a transient increase in lymphocyte oxidative stress. Results suggest this was unrelated to the alterations in the cellular composition of peripheral blood.     

Antioxidant enzyme activities,lipid peroxidation,and DNA oxidative damage: the effects of short-term voluntary wheel running

We examined the effect of voluntary exercise on antioxidant enzyme activities (catalase, glutathione peroxidase, superoxide dismutase) in skeletal muscle (hind- and forelimb) and heart of a model small mammal species: short-tailed field vole Microtus agrestis. In addition, DNA oxidation was determined in lymphocytes and hepatocytes using the comet assay and lipid peroxidation estimated in hindlimb muscle by measurement of thiobarbituric-acid-reactive substances. Voles (approximately 6 weeks old), exposed to a 16L:8D photoperiod (lights on 0500 h), ran almost continuously during darkness. We studied the effects of voluntary running over 1 or 7 days duration, with or without an 8-h rest period, on various biomarkers of oxidative stress compared to nonrunning controls. No differences were observed in antioxidant enzyme activities, except in heart total superoxide dismutase activity (P=0.037), with the lowest levels in 1- and 7-day runners at 0500 h. DNA oxidative damage, in lymphocytes or hepatocytes, and lipid peroxidation did not differ between groups. There was no evidence of any significant increase in any oxidative stress parameter in running individuals, despite having significantly elevated energy expenditures compared to sedentary controls.