Effects of CoQ10 supplementation and swimming training on exhaustive exercise-induced oxidative stress in rat heart.

This study examined the combined effects of swimming training and coenzyme Q10 (CoQ10) supplementation on exhaustive exercise-induced oxidative stress in rat heart. The study was carried out with 4-month-old young adult male Wistar rats. Sixty four rats were divided mainly into two groups: trained and control. Each group was further divided into four subgroups: rest, exhausted, rest with CoQ10, exhausted with CoQ10. The training program consisted of swimming one hour each day, five days a week, for six weeks. At the end of sixth week, rats in exhausted exercise group were forced to swim until exhaustion and then they were immediately sacrificed, while rats in rest group were sacrificed at rest. Training alone or in combination with CoQ10 supplementation reduced to increasing MDA levels due to exhaustive exercise in rat heart (p<0.05). The trained-rest with CoQ10 group showed lower 8-OHdG levels than the control-rest with CoQ10 group. Exhaustive exercise effect was significant on SOD activity. Exhaustive exercise increased GSH levels in control groups while decreased GSH levels in training groups (p<0.05). In conclusion, the results suggest that CoQ10 supplementation combined with training may inhibit lipid peroxidation and DNA damage in the heart tissue. Also, it can be said that SOD activity and GSH levels were not influenced by CoQ10 supplementation (Fig. 4, Tab. 1, Ref. 69).

Effects of treatment with coenzyme Q10 on exercised rat aorta.

In this study, the effect of long-term supplementation of coenzyme Q10 (CoQ10) on the responses of swim-trained rat aorta was investigated. Twenty-four adult male Wistar rats were divided into four groups: untrained, trained, untrained+CoQ10, and trained+CoQ10 group. In the trained groups rats swam for 60 min/day, five days/week for six weeks. The CoQ10 supplements were administered by intraperitoneal injection at a daily dose of 10 mg·kg-1 of body weight five days/week for six weeks. Swimming of the rats was performed in a container containing tap water. Rats were sacrificed and thoracic aortas were removed for ex vivo analysis after the last swimming session. The aortas were cut into rings 2.5 mm in length. Concentration-response curves for phenylephrine (PHE, 10-9-3×10-4 M) and potassium chloride (KCl, 5-100 mM) were isometrically recorded. The sensitivity and maximal responses to PHE and KCl of aortic rings obtained from trained rats were lower than those of untrained rats. CoQ10 supplementation decreased the responses to both vasoconstrictors in untrained and especially in trained groups. Although neither CoQ10 nor training did affect malondialdehyde (MDA) and protein carbonyl (PC) levels, creatine kinase (CK) activity decreased and superoxide dismutase (SOD) activity increased only with exercise training. Glutathione (GSH) levels increased in CoQ10 supplemented-untrained rats. In conclusion, our results suggest that CoQ10 supplementation may have beneficial effects during exercise.

Short duration exhaustive running exercise does not modify lipid hydroperoxide, glutathione peroxidase and catalase.

AIM: Oxidative stress occurs only when exercise is exhaustive and is independent of the absolute duration of exercise. In this study the effects of short duration (03:50 +/- 00:06 min) high-intensity exhaustive exercise on lipid peroxidation and antioxidant status were examined. METHODS: A total of thirty-seven male university students (23.9+/-0.6 years old) participated in this study. None was involved in a regular training program before the study. Intensities of exercises were determined according to the maximum slope and speed they could run in Bruce Test Protocol which is used for determining V.O2max of the participants. Just before and after the high intensity exhaustive running exercise test, venous blood was collected and centrifuged to separate the plasma. RESULTS: Lipid hydroperoxides (LOOH) did not change, glutathione peroxidase (GPx) decreased (2%) and catalase (CAT) increased (13%) at the pre and post exhaustive exercise test. These changes were not statistically significant (P>0.05). On the other hand, lactate dehydrogenase (LDH) levels significantly increased (31%) (P< 0.001). CONCLUSION: As a result, it may be claimed that short duration exhaustive exercise test produced no important changes in LOOH, GPx and CAT levels. And exhaustive exercise-induced oxidative stress may be related with exercise duration.

Adenosine A2 receptor occupancy regulates stimulated neutrophil function via activation of a serine/threonine protein phosphatase.

Adenosine modulates generation of superoxide anion by neutrophils via occupancy of specific adenosine A2A receptors. However, the intracellular signal transduction pathways by which occupancy of neutrophil adenosine A2A receptors inhibits superoxide anion generation (O2.-) are not well understood. We, therefore, tested the hypothesis that signaling at polymorphonuclear leukocyte (PMN) adenosine receptors proceeds via activation of a serine/threonine protein phosphatase (pp). Both the specific pp1 inhibitor calyculin A (10 nM) and the pp2A inhibitor okadaic acid (10 microM) enhanced O2.- generation (185 +/- 24 and 189 +/- 35% of control, respectively, p < 0.0001 for both, n = 8), as reported previously. Calyculin A, but not okadaic acid, completely reversed inhibition of stimulated O2.- generation by the adenosine A2 receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA; IC50 = 30 nM; p < 0.0001, analysis of variance). Calyculin A also reversed the adenosine receptor-mediated desensitization of bound chemoattractant receptors in neutrophils. Treatment of PMNs with NECA increased the pp1 activity of crude membrane preparations in a time- and dose-dependent fashion (EC50 = 40 nM; p < 0.001, analysis of variance, n = 5). NECA inhibited cytosolic protein phosphatase activity by 78 +/- 12% (p < 0.003, n = 6) but did not shift pp1 catalytic subunit from cytosol to plasma membrane. Similar changes were observed in neutrophil cytoplasts depleted of organelles and nucleus. Moreover, the selective protein kinase A inhibitor KT5720 (10 microM) reversed the capacity of dibutyryl cAMP but not NECA to increase pp1 activity (p < 0.01, n = 5) in keeping with its effects on O2.- generation. Western blot analysis of PMN subcellular fractions demonstrated the presence of pp1alpha and pp1gamma1 but not pp1gamma2 isotypes in both cytosol and plasma membrane but not in azurophil or specific granules. We conclude from these studies that signal transduction by adenosine in PMN proceeds via a novel pathway: cAMP-independent activation of a serine/threonine protein phosphatase in the plasma membrane.

Prevention and treatment of experimental autoimmune myasthenia gravis with anti-rabbit thymocyte serum and gammaglobulin in rabbits.

Twenty-two rabbits received Torpedo californica acetylcholine receptor (AChR) subcutaneously. Six rabbits were treated with 0.5 ml/kg/day of anti-rabbit thymocyte serum (ARTS), and four were treated with 5.0 mg/kg/day of anti-rabbit thymocyte gammaglobulin (ARTG) subcutaneously beginning concomitantly 1, 2 and 3 weeks after the initial AChR immunization. All 12 control animals died of experimental autoimmune myasthenia gravis (EAMG) within 52 days. None of the 10 treated rabbits developed clinical EAMG. ARTS- and ARTG-treated animals had significantly lower anti-AChR antibody titers than control animals at 3 weeks (pre-AChR booster, p < 0.01). At 6 weeks (post-AChR booster), only ARTS-treated animals had significantly lower titers than controls (p < 0.01). ARTS-treated animals developed sterile abscesses at injection sites, which were minimal in the ARTG-treated group. ARTS and ARTG prevent EAMG.

Idiotypic control of the immune response.

Anti-idiotypic antibodies are antibodies against the antigenic determinants (idiotypes) of an antibody's antigen-binding region. Anti-idiotypes can bind near (Ab2 gamma) or away (Ab2 alpha) from the antigen-combining site or can carry the internal image of the antigen (Ab2 beta). Idiotypes and anti-idiotypes have been described in T- and B-cell systems. They have been used in basic research to purify and characterize receptors and ligands against receptors, to treat tumors, to make vaccines and to diagnose and suppress the immune response. In experimental myasthenia gravis anti-idiotypes protect animals against the disease, block idiotype binding and share idiotypic specificities.