The red cell glutathione levels of 10 healthy volunteers who are accustomed to winter-swimming were measured before and after this short-term whole body exposition to hypothermic environment. From the increases of the erythrocytic level of oxidized glutathione (GSSG) and of GSSG: total glutathione ratio an extensive formation of oxygen free radicals during and following the exposition to the intensive cold stimulus was concluded. That is in accordance with the finding on the drastic decrease of the concentration of uric acid as an important radical scavenger of the human blood plasma. Furthermore, the initial erythrocytic concentrations of reduced glutathione (GSH) and GSSG of subjects accustomed to winter-swimming were compared with those of healthy control persons who are not accustomed to regular winter-swimming. The markedly increased concentration of GSH and the reduced GSSG:total glutathione ratio in the erythrocytes of winter-swimmers reflect the adaptation to a regular oxidative stress. This antioxidative adaptation is postulated as a new basic mechanism of the hardening by exposition to an intensive short-term cold stimulus often applied within the hydrotherapy.

BACKGROUND:Only limited data are available for evaluating the effects of the administration of grape seed extract (GSE) on the metabolic status of female volleyball players.

OBJECTIVES:This study was conducted to determine the effects of GSE administration on the metabolic status of female volleyball players.

METHODS:This randomized, double-blind, placebo-controlled clinical trial was performed among 40 female volleyball players. The subjects were randomly divided into two groups, with members of the test group (n = 20) taking 300 mg of GSE twice a day for eight weeks and members of the control group (n = 20) taking a placebo pearl for the same period. Fasting blood samples were taken before and after the eight-week intervention period in order to determine the related variables.

RESULTS:Supplementation with GSE resulted in a significant rise in the plasma glutathione (GSH) level (+265.5± 344.2 vs. +2.2 ± 378.2 µmol/L, P = 0.02), as well as a significant decrease in the malondialdehyde (MDA) level (-1.4 ± 2.0 vs. -0.2 ± 1.2 µmol/L, P = 0.01) when compared to the placebo group. In addition, when compared to the group that received the placebo, the subjects who received GSE hadsignificantly decreased serum insulin concentrations (-23.4 ± 23.4 vs. +1.8 ± 25.2 pmol/L, P = 0.002), a decreased homeostasis model of assessment for insulin resistance (HOMA-IR) (-0.7 ± 0.7 vs. +0.2 ± 0.9, P = 0.002), and an increased quantitative insulin sensitivity check index (QUICKI) (+0.01 ± 0.01 vs. -0.01 ± 0.02, P = 0.03). The administration of GSE had no significant effects on creatine phosphokinase (CPK), total antioxidant capacity (TAC), nitric oxide (NO), fasting plasma glucose (FPG), and lipid concentrations when compared with the administration of the placebo. However, after controlling for baseline NO levels, age, and baseline BMI, the changes in the plasma NO concentrations were significantly different between the two groups.

CONCLUSIONS:In conclusion, taking GSE for eight weeks had beneficial effects on the plasma GSH, MDA levels, and markers of insulin metabolism of female volleyball players.

The antioxidant N-acetyl cysteine (NAC) is a precursor of intracellular glutathione (GSH) and is also a well known as one of the chemopreventive agents which act through a variety of cellular mechanisms. We examined the effects of NAC on cell cycle progression in the pancreatic carcinoma cell lines, SW1990 and JHP1. Cells were incubated with or without NAC. Cell cycle distribution was analyzed by flow cytometry and immunoblotting. NAC suppressed cell proliferation in a concentration-dependent manner, whereas NAC increased intracellular glutathione content significantly in a dose-dependent manner. The percentage of cells in the G1 phase after treatment with NAC was significantly higher than the percentage seen for control cells. Cyclin D1 expression of carcinoma cells treated with NAC decreased remarkably compared with cells without NAC treatment. Thus, the antiproliferative effect of NAC by prolongation of the G1 phase in human pancreatic carcinoma cells shows its possible utility as an antitumor agent.

Neuropathic pain (NP) is caused by damage to the nervous system due to reactive oxygen spices (ROS) increase, antioxidants reduction, ATP production imbalance, and induction of apoptosis. In this investigation, we applied low-level laser 660 nm (photobiomodulation therapy) as a new strategy to modulate pain. In order to study the effects of photobiomodulation therapy (660 nm) on NP, chronic constriction injury (CCI) model was selected. Low-level laser of 660 nm was used for 2 weeks. Thermal and mechanical hyperalgesia were measuredbefore and after surgery on days 7 and 14, respectively. Paw withdrawal thresholds were also evaluated. Expression of p2x3, Bax, and bcl2 protein was measured by western blotting. The amount of glutathione (GSH) was measured in the spinal cord by continuous spectrophotometric rate determination method. The results are presented as mean ± SD. Statistical analysis of data was carried out using SPSS 21. CCI decreased the pain threshold, 2-week photobiomodulation therapy significantly increased mechanical and thermal threshold, decreased P2X3 expression (p < 0.001), and increased bcl2 expression (p < 0.01), but it was not effective on the Bax expression. We speculated that although photobiomodulation therapy increased ROS generation, it increased antioxidants such as GSH. Increase in bcl2 is another mitochondrial protection mechanism for cell survival and that pain relief and decrease in P2X3expression confirm it.

Two population-based, case-control studies have documented reduced risk of prostate cancer in men who consume cruciferous vegetables. Cruciferae contain high levels of the isothiocyanate sulforaphane. Sulforaphane is known to bolster the defenses of cells against carcinogens through up-regulation of enzymes of carcinogen defense (phase 2 enzymes). Prostate cancer is characterized by an early and near universal loss of expression of the phase 2 enzyme glutathione S-transferase (GST)-pi. We tested whether sulforaphane may act in prostatic cells by increasing phase 2 enzyme expression. The human prostate cancer cell lines LNCaP, MDA PCa 2a, MDA PCa 2b, PC-3, and TSU-Pr1 were treated with 0.1-15 microM sulforaphane in vitro. LNCaP was also treated with an aqueous extract of broccoli sprouts. Quinone reductase enzymatic activity, a surrogate of global phase 2 enzyme activity, was assayed by the menadione-coupled reduction of tetrazolium dye. Expression of NQO-1, GST-alpha, gamma-glutamylcysteine synthetase-heavy and -light chains, and microsomal GST was assessed by Northern blot analysis. Sulforaphane and broccoli sprout extract potently induce quinone reductase activity in cultured prostate cells, and this induction appears to be mediated by increased transcription of the NQO-1 gene. Sulforaphane also induces expression of gamma-glutamylcysteine synthetase light subunit but not the heavy subunit, and this induction is associated with moderate increases in intracellular glutathione levels. Microsomal and alpha-class glutathione transferases were also induced transcriptionally. Sulforaphane induces phase 2 enzyme expression and activity significantly in human prostatic cells. This induction is accompanied by, but not because of, increased intracellular glutathione synthesis. Our findings may help explain the observed inverse correlation between consumption of cruciferae and prostate cancer risk.

Ten healthy subjects who swim regularly in ice-cold water during the winter (winter swimming), were evaluated before and after this short-term whole body exposure. A drastic decrease in plasma uric acid concentration was observed during and following the exposure to the cold stimulus. We hypothesize that the uric acid decrease can be caused by its consumption after formation of oxygen radicals. In addition, the erythrocytic level of oxidized glutathione and the ratio of oxidized glutathione/total glutathione also increased following cold exposure, which supports this hypothesis. Furthermore, the baseline concentration of reduced glutathione was increased and the concentration of oxidized glutathione was decreased in the erythrocytes of winter swimmers as compared to those of nonwinter swimmers. This can be viewed as an adaptation to repeated oxidative stress, and is postulated as mechanism for body hardening. Hardening is the exposure to a natural, e.g., thermal stimulus, resulting in an increased tolerance to stress, e.g., diseases. Exposure to repeated intensive short-term cold stimuli is often applied in hydrotherapy, which is used in physical medicine for hardening.