Synergic Effect of Exercise and Lipoic Acid on Protection Against Kainic Acid Induced Seizure Activity and Oxidative Stress in Mice

Anti-convulsant effects of physical exercise and lipoic acid (LA), also referred to as thioctic acid with antioxidant activity, were investigated using chemical induced seizure model. We investigated the synergic effect of physical exercise and LA on kainic acid-induced seizure activity caused by oxidative stress. After 8 weeks of swimming training, body weight decreased and endurance capacity increased significantly compared to sedentary mice. Kainic acid (30 mg/kg, i.p.) evoked seizure activity 5 min after injection, and seizure activity peaked approximately 80 min after kainic acid treatment. Median seizure activity score in KA only treated group was 4.55 (range 0.5–5), 3.45 for “LA + KA” group (range 0.5–4.3), 3.12 for “EX + KA” group (range 0.05–3.4, p < 0.05 vs. “KA only” group), 2.13 for “EX + LA + KA” group (range 0.5–3.0, p < 0.05 vs. “EX + KA” group). Also, there was a synergic cooperation of exercise and LA in lowering the mortality in kainic acid treated mice (χ² = 5.45, p = 0.031; “EX + KA” group vs. “LA + EX + KA” group). In addition, the synergic effect of exercise and LA was found in PGx activity compared to separated treatment (“LA + EX + KA”: 37.3 ± 1.36; p < 0.05 vs. “LA + KA” and “EX + KA” group). These results indicate that physical exercise along with LA could be a more efficient method for modulating seizure activity and oxidative stress.     

Combined Low-Intensity Exercise and Ascorbic Acid Attenuates Kainic Acid-Induced Seizure and Oxidative Stress in Mice

Physical exercise and vitamins such as ascorbic acid (ASC) have been recognized as an effective strategy in neuroprotection and neurorehabilitatioin. However, there is a need to find an efficient treatment regimen that includes ASC and low-intensity exercise to diminish the risk of overtraining and nutritional treatment by attenuating oxidative stress. In the present study, we investigated the combined effect of low-intensity physical exercise (EX) and ASC on kainic acid (KA)-induced seizure activity and oxidative stress in mice. The mice were randomly assigned into groups as follows: “KA only” (n = 11), “ASC + KA” (n = 11), “Ex + KA” (n = 11), “ASC + Ex + KA” (n = 11). In the present study, low intensity of swimming training period lasted 8 weeks and consisted of 30-min sessions daily (three times per week) without tail weighting. Although no preventive effect of low-intensity exercise or ASC on KA seizure occurrence was evident, there was a decrease of seizure activity, seizure development (latency to first seizures), and mortality in “ASC + Ex + KA” compared to “ASC + KA”, “Ex + KA”, and “KA only” group. In addition, a preventive synergistic coordination of low-intensity exercise and ASC was evident in glutathione peroxidase and superoxide dismutase activity compared to separate treatment. These results suggest that low-intensity exercise and ASC treatment have preventive effects on seizure activity and development with alternation of oxidative status.     

Chronic Resveratrol Treatment Protects Pancreatic Islets against Oxidative Stress in db/db Mice

Resveratrol (RSV) has anti-inflammatory and anti-oxidant actions which may contribute to its cardiovascular protective effects. We examined whether RSV has any beneficial effects on pancreatic islets in db/db mice, an animal model of type 2 diabetes. The db/db and db/dm mice (non-diabetic control) were treated with (db-RSV) or without RSV (db-control) (20 mg/kg daily) for 12 weeks. After performing an intraperitoneal glucose tolerance test and insulin tolerance test, mice were sacrificed, the pancreas was weighed, pancreatic β-cell mass was quantified by point count method, and the amount of islet fibrosis was determined. 8-Hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, was determined in 24 h urine and pancreatic islets. RSV treatment significantly improved glucose tolerance at 2 hrs in db/db mice (P = 0.036), but not in db/dm mice (P = 0.623). This was associated with a significant increase in both pancreas weight (P = 0.011) and β-cell mass (P = 0.016). Islet fibrosis was much less in RSV-treated mice (P = 0.048). RSV treatment also decreased urinary 8-OHdG levels (P = 0.03) and the percentage of islet nuclei that were positive for 8-OHdG immunostaining (P = 0.019). We conclude that RSV treatment improves glucose tolerance, attenuates β-cell loss, and reduces oxidative stress in type 2 diabetes. These findings suggest that RSV may have a therapeutic implication in the prevention and management of diabetes.     

白灵菇多糖对运动小鼠氧化应激的影响

体外研究表明,白灵菇多糖具有较高的清除自由基能力。然而,白灵菇多糖在体内对运动引起的氧化应激的影响尚不清楚。本研究将100只SPF级雄性昆明小鼠随机分为5组,低剂量组、中剂量组和高剂量组昆明小鼠分别按照50 mg·kg^-1·d^-1、100 mg·kg^-1·d^-1和200 mg·kg^-1·d^-1的剂量灌胃白灵菇多糖溶液,对照组和模型组昆明小鼠灌胃等体积的蒸馏水,连续灌胃4周。研究显示,白灵菇多糖溶液以浓度依赖性方式提高了小鼠的力竭游泳时间(p<0.05)。白灵菇多糖以浓度依赖性方式降低了小鼠血清AST、ALT和CK水平,并显著减少了骨骼肌的病理变化(p<0.05)。白灵菇多糖以剂量依赖方式升高力竭游泳小鼠体内SOD、CAT和GSH-PX水平,并降低了MDA水平(p<0.05)。此外,对小鼠灌胃白灵菇多糖可以剂量依赖方式提高小鼠血清总抗氧化活性(p<0.05)。上述研究表明,白灵菇多糖可有效提高力竭游泳小鼠的抗疲劳能力,减轻运动引起的心肌、肝脏、骨骼肌和氧化应激损伤,提高机体的抗氧化能力。     

Effect of Diethyl Maleate Induced Oxidative Stress on Male Reproductive Activity in Mice: Redox Active Enzymes and Transcription Factors Expression

Signaling by tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE) is essential for the differentiation of monocytes/macrophages into osteoclasts. We show here that TRANCE selectively activates Rac1, but not Rac2 in osteoclast precursors. Expression of a dominant interfering mutant of TNF receptor-associated factor (TRAF)6 blocks TRANCE-mediated Rac1 activation, indicating that Rac1 lies downstream of TRAF6. Osteoclast precursors expressing a dominant negative Rac1N17 are defective in TRANCE-induced IKK activation and IκBα degradation resulting in inhibition of NFκB-dependent reporter gene activity. In addition, Rac1 acts upstream of TAK1 to induce NF-κB activation and is required for the normal differentiation of osteoclast precursors. Thus, Rac1 may represent a key regulator for differentiation of osteoclasts through the activation of NF-κB.     

脂肪组织氧化应激与运动干预

脂肪组织在调控代谢稳态和运动适应中扮演着重要的角色。肥胖引起的脂肪组织氧化应激是2型糖尿病与代谢综合征等的重要病理特征,是促进脂肪组织炎症和胰岛素抵抗的重要机制。氧化应激可以引起脂肪细胞趋化因子表达,募集炎症细胞浸润脂肪组织,炎症细胞分泌大量的炎症因子,并促进了局部和系统的胰岛素抵抗与慢性炎症。运动对肥胖相关的慢性代谢病的有效干预与运动的抗氧化效应相关。本文总结了氧化应激在脂肪组织炎症和胰岛素抵抗中的作用,以及运动对脂肪组织氧化应激的调控。     

低氧运动对Nrf2基因敲除大鼠运动能力和氧化应激的影响

Nrf2可调节多种抗氧化酶的表达,Nrf2的缺失可能影响机体的运动能力,而低氧可提高机体的抗氧化能力并改善运动能力。为了考察低氧运动对Nrf2基因敲除大鼠运动能力和氧化应激的影响,本研究分别在常氧和低氧环境(12%氧浓度)中对野生型大鼠和Nrf2敲除大鼠进行4周的跑台运动。研究显示,低氧运动可提高野生型大鼠的跑台运动力竭时间,Nrf2敲除可缩短大鼠的力竭时间;低氧运动可上调大鼠的Nrf2 m RNA表达量;Nrf2敲除明显抑制HIF-1α蛋白表达,而低氧运动可上调野生型和Nrf2敲除大鼠的HIF-1α蛋白表达;Nrf2敲除大鼠的骨骼肌ROS水平明显升高,并且低氧均可降低野生型和Nrf2敲除大鼠骨骼肌ROS水平。低氧运动可上调Nrf2敲除大鼠的CAT和GSH-PX蛋白表达。苏木精和伊红(HE)染色显示,Nrf2敲除大鼠在力竭跑台运动完成后出现更严重的骨骼肌病理改变,而低氧运动可减轻骨骼肌损伤。本研究认为,Nrf2敲除导致了大鼠骨骼肌中抗氧化酶的抑制及ROS的过量累积,从而造成了骨骼肌损伤并降低了运动能力。此外,低氧可通过上调Nrf2的表达,进而激活HIF-1α及抗氧化酶活性,从而提高运动能力,并防止骨骼肌损伤。     

In Vivo Esr Studies of Antioxidant Activity on Free Radical Reaction in Living Mice Under Oxidative Stress

In vivo antioxidant activity seems to be quite complicate due to multiple interaction with biomaterials and differs from results by in vitro experiments. In vivo estimation of antioxidant activity is performed by measuring TBA reactive substances in blood or hydrocarbon gases in breath, but these systems do not measure free radical reaction but the final products of oxidative reaction. In the present study, we applied in vivo ESR to evaluate antioxidant activity by monitoring the redox reaction of nitroxide radical and clearly found that the nitroxide is very susceptible to oxidative stress in vivo and quite useful to evaluate antioxidant activity non-invasively.     

Postnatal Methylmercury Exposure Induces Hyperlocomotor Activity and Cerebellar Oxidative Stress in Mice: Dependence on the Neurodevelopmental Period

During the early postnatal period the central nervous system (CNS) is extremely sensitive to external agents. The present study aims at the investigation of critical phases where methylmercury (MeHg) induces cerebellar toxicity during the suckling period in mice. Animals were treated with daily subcutaneous injections of MeHg (7 mg/kg of body weight) during four different periods (5 days each) at the early postnatal period: postnatal day (PND) 1–5, PND 6–10, PND 11–15, or PND 16–20. A control group was treated with daily subcutaneous injections of a 150 mM NaCl solution (10 ml/kg of body weight). Subjects exposed to MeHg at different postnatal periods were littermate. At PND 35, behavioral tests were performed to evaluate spontaneous locomotor activity in the open field and motor performance in the rotarod task. Biochemical parameters related to oxidative stress (levels of glutathione and thiobarbituric acid reactive substances, as well as glutathione peroxidase and glutathione reductase activity) were evaluated in cerebellum. Hyperlocomotor activity and high levels of cerebellar thiobarbituric acid reactive substances were observed in animals exposed to MeHg during the PND 11–15 or PND 16–20 periods. Cerebellar glutathione reductase activity decreased in MeHg-exposed animals. Cerebellar glutathione peroxidase activity was also decreased after MeHg exposure and the lowest enzymatic activity was found in animals exposed to MeHg during the later days of the suckling period. In addition, low levels of cerebellar glutathione were found in animals exposed to MeHg during the PND 16–20 period. The present results show that the postnatal exposure to MeHg during the second half of the suckling period causes hyperlocomotor activity in mice and point to this phase as a critical developmental stage where mouse cerebellum is a vulnerable target for the neurotoxic and pro-oxidative effects of MeHg.     

白藜芦醇减轻神经元氧化应激损伤的作用机制研究

目的:观察白藜芦醇(RSV)对过氧化氢(H2O2)所致的海马神经元HT22细胞损伤的保护作用,并探讨超氧化物歧化酶2(Mn-SOD)在其中的作用。方法:采用体外培养HT22小鼠海马神经元细胞系,H2O2作为损伤因素模拟氧化应激损伤。将细胞分为5组,分别为正常培养组(Control)、150μM H2O2损伤组(H2O2)、25μM白藜芦醇保护组(RSV+H2O2)、SOD2-si RNA干扰组(SOD2-si RNA+RSV+H2O2)和乱序RNA组(SC-si RNA+RSV+H2O2),药物暴露24 h后,应用MTT法检测HT22细胞活力、比色法检测乳酸脱氢酶(Lactate Dehydrogenase,LDH)释放量、相差显微镜观测细胞形态。结果:与对照组相比,H2O2组的活力显著下降(P0.05),LDH释放量明显增加(P0.05),细胞形态明显破坏;25μM的RSV显著恢复了HT22细胞的活力、减少了LDH释放、改善了细胞形态,而SOD2-si RNA显著逆转了RSV引起的上述保护作用,乱序RNA(SC-si RNA)未对上述保护作用产生明显影响。结论:白藜芦醇可能通过上调SOD2减轻H2O2对HT22细胞的氧化应激损伤。     

Effect of Shin Lengthening and Regular Exercise on Limb Arteries

The luminal diameter of arteries increases with the natural growth of the body. The wall elasticity and the luminal diameter of arteries also temporarily increased on shin lengthening by the Ilizarov technique in patients with limb-length discrepancy. Notwithstanding an increase in the supplied tissue mass, these parameters were not stabilized at a new, higher level. The luminal diameter was shown to depend on the contractility of the corresponding muscles. Regular training reduced the wall elasticity and increased its orthostatic change in choreography students. Athletes displayed a dependence of the popliteal artery lumen on the muscle contractility; however, the luminal diameter of the popliteal artery was relatively low in athletes.     

Effects of Organic Copper on Growth Performance and Oxidative Stress in Mice

Biological Trace Element Research - Copper (Cu) has been used as a feed additive for many years. However, high Cu amounts can cause oxidative stress and adversely affect animal performance. Such...     

蕨菜黄酮对染矽尘小鼠氧化应激及肺纤维化的影响

为探讨蕨菜黄酮对染矽尘小鼠的抗氧化应激及肺纤维的影响,采用超声雾化石英粉尘混悬液,使小鼠染尘,蕨菜黄酮(Pteridium aqulinum flavonoids,PAF)连续灌胃染尘小鼠3周,取血测血清中超氧化物歧化酶(superoxide dismutase,S0D)、丙二醛(malonaldehyde,MDA),并测肺组织中SOD、MDA、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、羟脯氨酸(hydroxyproline,Hyp),计算肺质量系数,取右肺下叶做病理组织观察;结果显示蕨菜黄酮组血及肺组织MDA值显著下降、SOD活力显著升高,肺组织GSH-Px活力显著升高,肺Hyp含量及肺指数显著下降,肺纤维化进程延缓,表明蕨菜黄酮对染矽尘小鼠具有较好的抗氧化应激效应,延缓了肺纤维化进程。     

Cardiac Energy Metabolism and Oxidative Stress Biomarkers in Diabetic Rat Treated with Resveratrol

Resveratrol (RSV), polyphenol from grape, was studied to evaluate its effects on calorimetric parameters, energy metabolism, and antioxidants in the myocardium of diabetic rats. The animals were randomly divided into four groups (n = 8): C (control group): normal rats; C-RSV: normal rats receiving RSV; DM: diabetic rats; and DM-RSV: diabetics rats receiving RSV. Type 1 diabetes mellitus was induced with administration of streptozotocin (STZ; 60 mg⁻¹ body weight, single dose, i.p.). After 48 hours of STZ administration, the animals received RSV (1.0 mg/kg/day) for gavage for 30 days. Food, water, and energy intake were higher in the DM group, while administration of RSV caused decreases (p<0.05) in these parameters. The glycemia decreased and higher final body weight increased in DM-RSV when compared with the DM group. The diabetic rats showed higher serum-free fatty acid, which was normalized with RSV. Oxygen consumption (VO₂) and carbon dioxide production (VCO₂) decreased (p<0.05) in the DM group. This was accompanied by reductions in RQ. The C-RSV group showed higher VO₂ and VCO₂ values. Pyruvate dehydrogenase activity was lower in the DM group and normalizes with RSV. The DM group exhibited higher myocardial β-hydroxyacyl coenzyme-A dehydrogenase and citrate synthase activity, and RSV decreased the activity of these enzymes. The DM group had higher cardiac lactate dehydrogenase compared to the DM-RSV group. Myocardial protein carbonyl was increased in the DM group. RSV increased reduced glutathione in the cardiac tissue of diabetic animals. The glutathione reductase activity was higher in the DM-RSV group compared to the DM group. In conclusion, diabetes is accompanied by cardiac energy metabolism dysfunction and change in the biomarkers of oxidative stress. The cardioprotective effect may be mediated through RVS''s ability to normalize free fatty acid oxidation, enhance utilization glucose, and control the biomarkers'' level of oxidative stress under diabetic conditions.     

Siparuna guianensis Essential Oil Antitumoral Activity on Ehrlich Model and Its Effect on Oxidative Stress

This work aims to evaluate the chemical composition, in vitro antioxidant capacity, and in vivo antitumoral activity of S. guianensis essential oil against Ehrlich's ascitic carcinoma and the effects on oxidative stress. The animals (Mus musculus) received a daily dose of S. guianensis oil orally (100 mg/kg) for 9 days. The main constituents of essential oil were curzerenone (16.4±1.5 %), drimenol (13.7±0.2 %), and spathulenol (12.4±0.8 %). S. guianensis oil showed antioxidant activity, inhibiting 11.1 % of DPPH radicals (95.7 mgTE/g); and 15.5 % of the β-carotene peroxidation. The group treated with S. guianensis showed a significant reduction in tumor cells (59.76±12.33) compared to the tumor group (96.88±19.15). Essential oil of S. guianensis decreased MDA levels and increased SOD levels in liver tissue. The essential oil of S. guianensis reduced oxidative stress, and showed antitumor and antioxidant activity, being characterized as a new chemical profile in the investigation of pathologies such as cancer.     

Protective Effect of Artemisia annua L. Extract against Galactose-Induced Oxidative Stress in Mice

Artemisia annua L. (also called qinghao) has been well known as a source of antimalarial drug artemisinins. In addition, the herb was reported to have in vitro antioxidative activity. The present study investigated the protective effect of aqueous ethanol extract of Qinghao (AA extract) against D-galactose-induced oxidative stress in C57BL/6J mice. Feeding AA extract-containing diet lowered serum levels of malondialdehyde and 8-OH-dG that are biomarkers for lipid peroxidation and DNA damage, respectively. Furthermore, AA extract feeding enhanced the activity of NQO1, a typical antioxidant marker enzyme, in tissues such as kidney, stomach, small intestine, and large intestine. In conclusion, AA extract was found to have antioxidative activity in mouse model.