The effect of selenium on the tissue sulfhydryl group content and lipid peroxide-destorying enzyme system in the liver, kidney and testis of rat treated with mercury was investigated. The male rats were injected s.c. with HgCl2 (10 micromoles/kg BW) and orally received Na2SeO3 (13 micromoles/kg BW) simultaneously. After 3 days, liver, kidney and testis were removed and analyzed. Mercury decreased the total sulfhydryl group content in the kidney by 25% and the total glutathione content in the kidney and testis by 50% and 36%, respectively, with no changes in other tissues. There was 12% increase in the total sulfhydryl group but not in the total glutathione content in kidney by a simul-taneous treatment of Se and Hg. Glutathione peroxidase (GSH-Px) activities were decreased by 63% in the liver and 69% in the kidney, and glutathione reductase (GSH-Rd) activity was increased in the tests by 16% by the Hg treatment with no changes in Other tissues. Hg had no effect upon glutathione-S-transferase activities in all organs examined. Simultaneous Se treatment increased GSH-Rd activity in the kidney by 23% and GSH-Px activities in liver and kidney by 24% and 21%, respectively, compared to the Hg-treated group. These data indicate that the alleviation of Hg toxicity by Se treatment is well correlated with the protein sulfhydryl group content and GSH-Px activity.
Animal ; Glutathione/metabolism* ; Glutathione Peroxidase/analysis ; Glutathione Reductase/analysis ; Male ; Mercury/toxicity* ; Rats ; Selenium/pharmacology* ; Sulfhydryl Compounds/analysis*

AIMTo explore a role of G6PD in replenishment of intracellular GSH during oxidative stress.

METHODSIn vitro Raji cell was cultured, intracellular GSH levels and G6PD, GR, GPX activities were determined at different time points after PMS treatment when G6PD activity was inhibited or not by DHEA.

RESULTSIntracellular GR, GPX, G6PD activities elevated significantly combined with GSH level decreased dramatically before 30 minutes, replenished gradually after 30 minutes and restore normal levels about 6 h after PMS treatment when G6PD was not inhibited. No change in GR and significant increase in GPX activity were shown following depleted GSH after PMS treatment when G6PD was inhibited by DHEA.

CONCLUSIONG6PD contributes to replenish intracellular GSH and is a critical factor regulating GSH levels during oxidative stress.

Cell Line, Tumor ; Glucosephosphate Dehydrogenase ; metabolism ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Humans ; Oxidation-Reduction ; Oxidative Stress ; Receptors, Peptide ; metabolism

Ferroptosis is an iron-dependent cell death pathway that is different from apoptosis, pyroptosis, and necrosis. The main characteristics of ferroptosis are the Fenton reaction mediated by intracellular free divalent iron ions, lipid peroxidation of cell membrane lipids, and inhibition of the anti-lipid peroxidation activity of intracellular glutathione peroxidase 4 (GPX4). Recent studies have shown that ferroptosis can be involved in the pathological processes of many disorders, such as ischemia-reperfusion injury, nervous system diseases, and blood diseases. However, the specific mechanisms by which ferroptosis participates in the occurrence and development of acute leukemia still need to be more fully and deeply studied. This article reviews the characteristics of ferroptosis and the regulatory mechanisms promoting or inhibiting ferroptosis. More importantly, it further discusses the role of ferroptosis in acute leukemia and predicts a change in treatment strategy brought about by increased knowledge of the role of ferroptosis in acute leukemia.
Humans ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism* ; Ferroptosis ; Cell Death ; Iron/metabolism* ; Leukemia, Myeloid, Acute

Reactive oxygen species (ROS) are produced under oxidative stress, such as high oxygen concentration and during the metabolic consumption of oxygen molecules. Male reproductive tissues appear to be continuously exposed to ROS produced by active metabolism. In addition, spermatozoa must pass through a high oxygen environment during the mating process. Thus, to maintain viable reproductive ability, a protective mechanism against oxidative stress is of importance. Here, we overview our current understanding of the cooperative function of antioxidative and redox systems that are involved in male fertility. Superoxide dismutase and glutathione peroxidase are major enzymes that scavenge harmful ROS in male reproductive organs. In turn, glutathione and thioredoxin systems constitute the main redox systems that repair oxidized and damaged molecules and also play a role in regulating a variety of cellular functions. While glutathione functions as an antioxidant by donating electrons to glutathione peroxidase and thioredoxin donates electrons to peroxiredoxin as a counterpart of glutathione peroxidase. In addition, aldo-keto reductases, which detoxify carbonyl compounds produced by oxidative stress, are present at high levels in the epithelia of the genital tract and Sertoli cells of the testis. Since these systems are involved in cross-talk, a comprehensive understanding will be required to maintain the physiological functions of male reproductive system.
Animals ; Antioxidants ; metabolism ; Catalase ; metabolism ; Genitalia, Male ; enzymology ; metabolism ; Glutathione ; biosynthesis ; Glutathione Peroxidase ; metabolism ; Humans ; Male ; Oxidation-Reduction ; Oxidative Stress ; physiology ; Oxidoreductases ; metabolism ; Superoxide Dismutase ; metabolism ; Thioredoxins ; metabolism

BACKGROUND: The product of oxygen-free radicals inf1ict oxidative injuries on healthy cells. Antioxidants such as superoxide dismutase(SOD), glutathione peroxidase, and reduced glutathione(GSH) are present in almost all cells and play important roles in metabolism, transport, and cellular protection. We measured blood GSH levels in healthy controls and patients with non insulin dependent diabetes mellitus(NIDDM) for evaluation of the clinical usefulness of GSH. METHODS: Erythrocyte GSH levels were measured in fifty healthy controls and thirty NIDDM patients with diabetic retinopathies by Beutler's method. We also tested within-run precision, between-run precision, linearity and recovery rate to evaluate this method measuring erythrocyte GSH levels. RESULTS: The GSH levels (mean +/-SD) of NIDDM patients (5.03+/-0.67mumo1/Hb) were significantly lower than those of healthy control group (6.46+/-0.85mumo1/Hb)(P<0.001). The results of within-run precision and between-run precision when stored at 4degrees Cwere excellent (coefficient of variation were 2.79% and 2.42%, respectively), however, when stored at the room temperature the GSH levels were sharply declined. The linearity and recovery rate were acceptable. CONCLUSIONS: The prescision, linearity, and recovery rate of GSH measurement were excellent. The GSH levels in NIDDM patient group were reduced, and this probably contributes to the defective defense mechanism against increased oxidative stress. Additional measurement of other antioxidants such as superoxide dismutase and glutathione Peroxidase may be required to clarify the pathologic significance of glutathione metabolism in various diseases.
Antioxidants ; Diabetes Mellitus, Type 2 ; Diabetic Retinopathy ; Erythrocytes* ; Glutathione Peroxidase ; Glutathione* ; Humans ; Insulin ; Metabolism ; Oxidative Stress ; Superoxide Dismutase ; Superoxides

The physiological roles of the glutathione(GSH)/glutathione peroxidase(GPx) system in protecting microbial cells against oxidative stress were reviewed. In eukaryotic model microbe Saccharomyces cerevisiae,this system is obligatory in maintaining the redox balance and defending the oxidative stress. However, the GSH/GPx system only conditionally exists in prokaryotes. Namely,for those prokaryote bacteria containing glutathione reductase and GPx, e.g. Haemophilus influenzae and Lactococcus lactis, by taking up GSH, they might develop a conditional GSH-dependent GPx reduction system, which conferred cells a stronger resistance against oxidative challenge.
Glutathione ; metabolism ; physiology ; Glutathione Peroxidase ; metabolism ; physiology ; Glutathione Reductase ; physiology ; Haemophilus influenzae ; physiology ; Lactococcus lactis ; physiology ; Oxidative Stress ; physiology ; Saccharomyces cerevisiae ; enzymology ; physiology

BACKGROUNDThe optimal time window for the administration of hypothermia following cerebral ischemia has been studied for decades, with disparity outcomes. In this study, the efficacy of mild brain hypothermia beginning at different time intervals on brain endogenous antioxidant enzyme and energy metabolites was investigated in a model of global cerebral ischemia.

METHODSForty-eight male Sprague-Dawley rats were divided into a sham-operated group, a normothermia (37°C - 38°C) ischemic group and a mild hypothermic (31°C - 32°C) ischemia groups. Rats in the last group were subdivided into four groups: 240 minutes of hypothermia, 30 minutes of normothermia plus 210 minutes of hypothermia, 60 minutes of normothermia plus 180 minutes of hypothermia and 90 minutes of normothermia plus 150 minutes of hypothermia (n = 8). Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model for 20 minutes and mild hypothermia was applied after 20 minutes of ischemia. Brain tissue was collected following 20 minutes of cerebral ischemia and 240 minutes of reperfusion, and used to measure the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), reduced glutathione (GSH) and adenosine triphosphate (ATP).

RESULTSMild hypothermia that was started within 0 to 60 minutes delayed the consumption of SOD, GSH-Px, GSH, and ATP (P < 0.05 or P < 0.01) in ischemic tissue, as compared to a normothermic ischemia group. In contrast, mild hypothermia beginning at 90 minutes had little effect on the levels of SOD, GSH-Px, GSH, and ATP (P > 0.05).

CONCLUSIONSPostischemic mild brain hypothermia can significantly delay the consumption of endogenous antioxidant enzymes and energy metabolites, which are critical to the process of cerebral protection by mild hypothermia. These results show that mild hypothermia limits ischemic injury if started within 60 minutes, but loses its protective effects when delayed until 90 minutes following cerebral ischemia.

Adenosine Triphosphate ; metabolism ; Animals ; Antioxidants ; metabolism ; Brain Ischemia ; enzymology ; metabolism ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Hypothermia, Induced ; Male ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Temperature

Glutathione (GSH) is a well-known antioxidative cellular component which is ubiquitous in nature. Several enzymes involved in GSH metabolism and recycling have been found to play important roles in detoxification of xenobiotics and free radicals. In this study, total GSH content, activity of GSH peroxidase and GSH reductase were measured in liver and kidney of cisplatin treated rats. Total GSH content (mM/g protein) of liver was higher in cisplatin treated rats (1.51±0.28) than of nontreated control (0.95±0.28), and in kidney, it was also higher in cisplatin treated rats (0.87±0.20) than that of control (0.68±0.14). The activity of GSH peroxidase (µM/mg protein/min) was lower in liver of cisplatin treated rats (348.0±18.54) than that of control (415.5±53.15), in kidney it was increase din cisplatin treated rats (380.5±51.86) compared to control (327.3±20.36). The activity of GSH reductase (µM/mg protein/min) was higher in liver of cisplatin treated rats (3.09±0.88) than that of control (2.28±0.61), in kidney it was also higher in cisplatin treated rats (8.50±2.62) than that of control (3.30±1.10). In summary, detoxification of ciplatin was revealed lesser effect in kidney as show increasion of GSH peroxidase and reductase and detoxification of cisplatin was expressed effectively in liver by increasing of GSH content and decreasing GSH peroxidase.
Animals ; Cisplatin* ; Free Radicals ; Glutathione* ; Kidney* ; Liver* ; Metabolism* ; Oxidoreductases ; Peroxidase ; Rats* ; Recycling ; Xenobiotics

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.
Brain Neoplasms ; Glioblastoma ; Glioma/diagnosis* ; Glutathione Peroxidase/metabolism* ; Humans ; Peroxidases ; Prognosis ; Proportional Hazards Models

For a long time, the morbidity and mortality rates of hepatocellular carcinoma (HCC) have remained high. Since the concept of ferroptosis was introduced in 2012, researchers' perspectives have shifted toward finding novel ferroptosis-related treatment strategies, especially for tumors that are resistant to apoptosis. In recent years, there have been an increasing number of studies on ferroptosis, and these studies have found that ferroptosis has great potential and promise for cancer treatment. Ferroptosis is a kind of regulated cell death (RCD); unlike apoptosis, ferroptosis is an iron-dependent type of RCD driven by lipid peroxidation. The whole process of ferroptosis mainly revolves around three pathways (system xc-/ glutathione peroxidase 4 [GPX4]), lipid peroxidation, and iron metabolism), which are also regulated by various metabolic factors. This review will attempt to analyze the relationship between the system xc-/GPX4 pathway, lipid peroxidation, iron metabolism, and ferroptosis from three aspects (triggering, execution, and regulation), and the regulatory factors for ferroptosis will be summarized. In this review, we will also illustrate the relationship between ferroptosis and tumors as well as its application in tumors from the perspective of HCC. Finally, we will summarize the current limitations and needs and provide perspectives related to the focus of development in the future.
Humans ; Ferroptosis ; Carcinoma, Hepatocellular/metabolism* ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism* ; Cell Death ; Liver Neoplasms/metabolism* ; Lipid Peroxidation ; Iron/metabolism*