Extensive exercise is not harmful in amyotrophic lateral sclerosis

Whether physical activity increases risk or promotes progression of motor neurone degeneration in amyotrophic lateral sclerosis (ALS) is still debated. Current pathophysiological hypotheses include excitotoxicity, oxidative stress and increased calcium loads as causes of selective degeneration of vulnerable motor neurones. Vigorous exercise might amplify these factors by increasing firing rates at motor neurones. To test this hypothesis, we constrained a transgenic mouse model of ALS overexpressing the mutant human form of the Cu/Zn superoxide dismutase-1 (SOD-1) to a lifetime exercise on motor-driven running wheels for 10 h daily (active group, n = 12). Onset and progression of disease were assessed by grip strength, stride length and tight rope test. Data were compared with SOD-1 mice placed in running wheels set to slow speed (sedentary group, n = 13). Untreated SOD-1 mice were an additional control group (n = 12). We found no differences in disease onset, which was determined by a change-point analysis using an iterative fitting of segmented linear regression models, or in disease progression. However, the running group showed a non-significant 6-day improvement in survival (133.7 +/- 3.2 days) compared with the sedentary group (127.2 +/- 3.2 days) and a 4-day improvement compared with the control group (129.1 +/- 2.5 days). We demonstrate that a lifetime of vigorous exercise does not promote onset or progression of motor degeneration in SOD-1-mediated ALS. Moreover, the results suggest that the level of excitatory input and calcium turnover at motor neurones, both of which should be increased by running activity, do not interfere with the pathophysiology of SOD-1-mediated ALS.     

Selenium diet-supplementation improves cocaine-induced myocardial oxidative stress and prevents cardiac dysfunction in rats

Chronic cocaine abuse causes cardiac dysfunction and induces oxidative stress. The goal of this study was to evaluate whether an enhanced antioxidant pool, induced by the administration of selenium, may prevent the myocardial dysfunction induced by cocaine. Cocaine was administered for 7 days (15 mg/kg/day, i.p.) to rats pretreated for 4 weeks with selenium (1.16 mg/L/day, p.o.). Cardiac function was evaluated by cardiac index and left ventricular (LV) fractional shortening (FS) measured by echocardiography. The redox ratio and enzymatic activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured in the LV myocardium. Cocaine administration induced a cardiac dysfunction, as evidenced by a decrease in cardiac index and LV FS as well as by an increase in LV diameters. Moreover, antioxidant markers and redox ratio were altered in rats after cocaine exposure. Selenite supplementation induced a significant limitation of cardiac index and FS alterations observed after cocaine administration. This improvement in cardiac function was associated with a redox ratio recovery while SOD and GPX activities remained unchanged. Thus, selenite reversed both the oxidative stress and the contractile dysfunction induced by cocaine administration. These results suggest a major role of oxidative stress in the cocaine-induced cardiotoxicity.     

A yang-promoting Chinese herbal suppository preparation enhances the antioxidant status of red cells in male human subjects

In the 16-week pilot study, the effect of a Yang-promoting Chinese herbal suppository preparation (VI-28) on the red cell antioxidant status was examined in 31 healthy male subjects aged 41-66 years old. VI-28 treatment for 12 weeks (one suppository (0.3 g) daily for week 1-4; one every 2 days for week 5-8; one every 3 days for week 9-12) produced a time/dose-dependent alteration in red cell antioxidant status. The VI-28-induced change is characterized by a slight depletion in cellular reduced glutathione (GSH) level and a decrease in susceptibility to peroxide-induced lipid peroxidation as well as increases in catalase (CAT) and Cu-Zn-superoxide dismutase (SOD) activities. While a reversal trend of change was observed in cellular GSH level, the susceptibility to lipid peroxidation as well as the CAT activity after the cessation of treatment for 4 weeks, the SOD activity exhibited a protracted increase. The results indicate that VI-28 treatment enhances red cell antioxidant status in male subjects. The beneficial effect of VI-28 treatment on red cells may re fl ect a corresponding change in antioxidant status of peripheral tissues.     

Study of serum levels of superoxide dismutase in preeclampsia and eclampsia: role of the test as a predictive tool

AIM: To report serum levels of superoxide dismutase in women with preeclampsia and eclampsia. To document the use of the value as a predictive tool for deciding the time of onset of subsequent convulsions with fulminating eclampsia and use of the value as a marker for obstetric intervention in clinical severe preeclampsia and eclampsia. METHODS: Superoxide dismutase concentration was measured in a consecutive study in sera of women admitted in obstetric ward for preeclampsia and eclampsia, and compared with sera of normotensive, healthy pregnant women in third trimester. Three mL venous blood was subjected to superoxide dismutase estimation by pyrogallol autoxidation method. RESULTS: We found statistically significant difference (P < 0.05) in mean superoxide dismutase levels of normotensive pregnant women; and preeclamptic and eclamptic subjects, no statistically significant difference was found in between value of enzyme in preeclampsia and eclampsia (P > 0.05). Superoxide dismutase levels in two pregnancy outcomes; live births and still births, shows significant difference (P < 0.05), being 1.03 U/mL and 0.52 U/mL, respectively. The comparison of values before delivery and after delivery showed highly statistically significant difference (P < 0.001) in both groups separately. The cut-off value of serum superoxide dismutase 0.52 U/mL has sensitivity 68.5%, specificity 59.5% and negative predictive value of 78.6%, for predicting the fetal death as outcome of pregnancy with severe grade of disease. CONCLUSION: We found low levels of serum superoxide dismutase, less than 0.52 U/mL, being the predecessor of fulminating eclampsia. Our results support this predictive value of serum superoxide dismutase level as important in deciding the time of intervention as termination of pregnancy.     

Gaseous superoxide potentiation of the effect of nonnarcotic analgesics in low doses

The action of inhalation of gaseous superoxide on the effects of low doses of nonnarcotic analgesics was studied on volunteers in the little finger compression test. After administration of placebo, inhalation of gaseous superoxide produced a negligible transient decrease in pain tolerance threshold. Inhalation of gaseous superoxide potentiated the effects of threshold doses of novalgin and aspirin and prolonged their action, but did not modulate the analgesic effect of diclofenac. It is assumed that the potentiating effect of superoxide on the action of analgesics is related to inhibition of monoamine oxidases leading to accumulation of monoamines in the brain.     

Relationship between oxidative stress and extrinsic coagulation pathway in haemodialyzed patients

Enhanced oxidative stress (SOX), endothelial dysfunction and haemostatic abnormalities are common in end-stage renal failure patients undergoing maintenance haemodialysis (HD). We studied associations among circulating immunoreactive total lipid peroxides as a marker of short-time SOX, autoantibodies against oxidized LDL as a surrogate of prolonged SOX, copper/zinc superoxide dismutase (Cu/Zn SOD) as a major antioxidant enzyme, tissue factor (TF) as a principal initiator of extrinsic coagulation pathway counteracted by its inhibitor (TFPI), and prothrombin fragment 1+2 (F 1+2) as a surrogate of activated haemostasis.

Pre-dialysis blood levels of all the markers studied were higher in 24 clinically stable HD patients compared to 11 healthy controls. Spearman's correlations among the three SOX markers were positive but nonsignificant in both HD patients and controls. In HD subjects, increased Cu/Zn SOD levels directly correlated with those of TF (rho=0.551, p=0.005) and TFPI (rho=0.501, p=0.001); the coagulation markers were also positively associated with each other (rho=0.663, p=0.0004). In healthy subjects, the relations between Cu/Zn SOD, TF and TFPI levels were inverse but not significant, and the direct association between TF and TFPI was nonsignificant either.

In conclusion, increased plasma levels of Cu/Zn SOD, the antioxidant enzyme with emerging endothelial cell-protective and antithrombotic properties, may be a novel part of the system counteracting activated extrinsic coagulation system in maintenance HD patients.     

Effects of Epigallocatechin-3-gallate on lead-induced oxidative damage

Recent studies have shown that lead (Pb) could disrupt the prooxidant/antioxidant balance of tissue which leads to biochemical and physiological dysfunction. Epigallocatechin-3-gallate (EGCG), a catechin polyphenols component, is found to be an effective antioxidant. The present study investigated whether EGCG administration could reverse the changes on redox states in rat hippocampus caused by lead exposure. The association between redox status changes and long-term potentiation (LTP) in CA1 area of hippocampus were also examined. Wistar rats exposed to lead from postnatal day 1 were followed by 10 days of EGCG (10, 25 and 50 mg/kg) administration through intraperitoneally (ip), and the rats were sacrificed for experiments at the age of 21–23 days. The experimental results showed that glutathione (GSH) and superoxide dismutase (SOD) activity decreased accompanied with LTP amplitude decrease in CA1 area of hippocampus in the lead-exposed group. EGCG supplementation following lead intoxication resulted in increases in the GSH and SOD levels and increases in the LTP amplitude. Malondialdehyde (MDA) levels, a major lipid peroxidation byproduct, increased following lead exposure and decreased following EGCG treatment. In hippocampal neuron culture model, lead exposure (20 μM) significantly inhibited the viability of neurons which was followed by an accumulation of ROS and a decrease of mitochondrial membrane potential (ΔΨ_m). Treatment by EGCG (10–50 μM) effectively increased cell viability, decreased ROS formation and improved ΔΨ_m in hippocampal neurons exposed to lead. These observations suggest that EGCG is a potential complementary agent in the treatment of chronic lead intoxication through its antioxidative character.     

Exacerbative role of vitamın A on radiation damage in vivo

Purpose In our study, after applying a single dose of 612 cGy irradiation, we aimed to observe the role of free radicals on tissue damage in liver caused by irradiation, by measuring the nitric oxide (NO) level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities, and the amount of thiobarbituric acid reactive substance (TBARS), which is an indicator of free-radical damage. On the other hand we investigated whether tissue damage can be prevented by vitamin A or not. Materials and methods The study was performed on three groups: (1) the control group, (2) the group to which irradiation was administrated, and (3) the group which was given irradiation + vitamin A. The irradiation group of animals was given a single dose of gamma irradiation at a sublethal dose. In the group to which both irradiation and vitamin A were administered, vitamin A was given for 2 days prior to irradiation. The amount of NO was measured by electron spin resonance (ESR) spectroscopy, whereas SOD, GPx and TBARS were measured by spectrophotometry. Results and conclusion As a result of irradiation-mediated tissue damage in liver, we observed a NO loss and an increase in TBARS amount. Administration of vitamin A before irradiation resulted in an increase in both NO and TBARS and a decrease in SOD and GPx enzyme activities. Together, these data indicate that vitamin A may play an exacerbative role in free-radical-mediated tissue damage.     

固本保元浸膏敷脐对大鼠溃疡性结肠炎氧自由基及其清除作用的影响

目的:研究固本保元浸膏对溃疡性结肠炎治疗作用.方法:应用大鼠溃疡性结肠炎的模型,给予固本保元浸膏敷脐,观察固本保元浸膏(GE)对大鼠血液和组织中氧自由基清除能力.结果:研究表明,GE能提高血液和组织中SOD及GSH-PX活性,降低LPO的含量,与病理组比较有显著差异(p＜0.01,P＜0.001).结论:固本保元浸膏具有抗自由基及其清除的能力.     

超氧化物歧化酶在卡那霉素耳中毒中的作用

作者应用羟胺法，观察了卡那霉素（ＫＭ）耳中毒时豚鼠耳蜗组织超氧化物歧化酶（ＳＯＤ）、听神经复合动作电位及微音器电位变化。结果显示：正常ＳＯＤ活力为２４２．２５±４３．１０亚硝酸单位／毫克蛋白（Ｎｕ／ｍｇ．ｐｒｏｔｅｉｎ）；ＫＭ组的ＳＯＤ活力增加到３１３．９２±３５．５９Ｎｕ／ｍｇ．ｐｒｏｔｅｉｎ（Ｐ＜０．０１）．结合耳蜗电图变化对结果进行了讨论，认为脂质过氧化反应很可能参与了ＫＭ耳中毒过程。