Glutathione Supplementation Research Articles

Glutathione and Selenium Supplementation Attenuates Liver Injury in Diethylnitrosamine-Induced Hepatocarcinogenic Mice by Enhancing Glutathione-Related Antioxidant Capacities.

Excess oxidative stress and inadequate antioxidant capacities are critical features in the development of hepatocellular carcinoma. This study aimed to determine whether supplementation with glutathione (GSH) and/or selenium (Se), as antioxidants, attenuates diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. C57BL/6J male mice were randomly assigned to control, DEN, DEN + GSH, DEN + Se, and DEN + GSH + Se groups for 20 weeks. Daily supplementation with GSH and/or Se commenced in the first experimental week and continued throughout the study. DEN was administered in weeks 2-9 and 16-19 of the experimental period. DEN administration induced significant pathological alterations of hepatic foci, evidenced by elevated levels of liver function, accompanied by high malondialdehyde (MDA) levels; low GSH levels; and glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) activities. Supplementation with GSH and Se significantly ameliorated liver pathological changes, reducing liver function and MDA levels while increasing GSH levels and GPx, GR, and GST activities. Notably, combined supplementation with GSH and Se more effectively increased the GSH/glutathione disulfide ratio and GPx activity than individual supplementation. Supplementation with GSH and Se attenuated liver injury in DEN-induced hepatocarcinogenic mice by enhancing GSH and its related antioxidant capacities, thereby mitigating oxidative damage.

Ameliorative impact of glutathione supplementation on cyclophosphamide-induced hepatic toxicity in rats.

Ameliorative impact of glutathione supplementation on cyclophosphamide-induced hepatic toxicity in rats.

The effect of reduced L-glutathione supplementation on TNF-α, hs-CRP, and neutrophil-lymphocyte ratio in maintenance hemodialysis patients.

Cardiovascular disease is the main cause of mortality in patients with chronic kidney disease stage 5 on dialysis (CKD-5D). High sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and neutrophil-lymphocyte ratio (NLR) are several inflammatory parameters associated with high cardiovascular events in CKD-5D. The main aim of this study was to evaluate the effect of reduced L-glutathione supplementation on serum hs-CRP, TNF-α, and NLR in patients with CKD-5D. This study is a quasi-experimental research with one group pretest-posttest design. Subjects included were patients with CKD-5D who routinely underwent hemodialysis therapy two times a week in Hasan Sadikin General Hospital. Serum hs-CRP, TNF-α, and NLR levels were obtained before and after the intervention of reduced L-glutathione supplementation dosing of one thousand milligrams a day for four weeks. Statistical analysis was then conducted using the Wilcoxon test. There were 26 hemodialysis patients included in the study, with a median age of 43 years and a male predominance. There was a significant decrease in serum TNF-α level after reduced L-glutathione supplementation for 4 weeks, 5.40 (-10.80-0.00) pg/mL, p = 0.002. However, there was no statistically significant decrease in either serum hs-CRP level, 0.40 (-0.70-0.80) mg/L (p = 0.656), or NLR with a difference of 0.55 (0.30-1.00) p = 0.055. Exogenous oral reduced glutathione supplementation for four weeks significantly reduced TNF-α level, but no significant decrease in hs-CRP level and NLR in patients with CKD-5D.

The impact of oral glutathione supplementation enhanced with bioavailability boosters on oxidative damage and glycated hemoglobin (HBA1C) levels in type 2 diabetes patients: A randomized, double-blind, placebo-controlled study

The impact of oral glutathione supplementation enhanced with bioavailability boosters on oxidative damage and glycated hemoglobin (HBA1C) levels in type 2 diabetes patients: A randomized, double-blind, placebo-controlled study

Abstract C037: Characterization of cysteine dependency implicates glutathione metabolism as a critical adaptation axis in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that is highly malignant and lethal. The treatment options are limited, contributing to its high mortality rate. PDAC is known to have profound metabolic alterations that enable its growth and survival. Here, we screened for amino acid dependency in PDAC cell lines and found that the cells cluster into cysteine highly dependent, moderately dependent, and independent cells. In the highly dependent cells, cysteine deprivation reduces viability by ∼90%, which could be rescued by glutathione (GSH) supplementation. Metabolomics revealed that cysteine deprivation led to GSH depletion, suggesting an impairment in the GSH pathway machinery in these cells. Consistently, most metabolite intermediates in the GSH pathway are downregulated in the cysteine-reliant PDAC cell lines compared to cell lines that resist cysteine deprivation, and those cells showed higher sensitivity to oxidative stress induction. Bioinformatics analysis of multiple PDAC tumor gene expression datasets indicated that the GSH pathway is strongly upregulated in PDAC and correlates with proliferation, metastasis, and oncogenic KRAS upregulation. Using CRISPR/Cas9, we found that the knockout of GSH genes enhanced sensitivity to oxidative stress. Our data implicate the GSH pathway as a critical nexus to be targeted to overcome metabolic adaptation in PDAC. Citation Format: Chiamaka J Ezeh, Matthew H Ward, Chesta Jain, Verodia Charlestin, Daeho D Kim, Andrew Yang, Maya Nassif, Nneka Mbah, Peter Sajjakulnukit, Anthony Andren, Li Zhang, Marina Pasca di Magliano, Costas A Lyssiotis, Zeribe C Nwosu. Characterization of cysteine dependency implicates glutathione metabolism as a critical adaptation axis in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C037.

Effect of Glutathione Supplementation in Cryoprotectant Modification on Tyrosine Phosphorylation, Acrosin Expression and Acrosome Reaction of Post-Thawing Spermatozoa Quality

Effect of Glutathione Supplementation in Cryoprotectant Modification on Tyrosine Phosphorylation, Acrosin Expression and Acrosome Reaction of Post-Thawing Spermatozoa Quality

The Role of Glutathione Administration in the Treatment of Infertility Men

Lipid peroxidation negatively affects sperm function by decreasing the number of motile sperm in the reproductive tract, which is caused by a disruption in the balance of sex hormones that regulate male fertility. A total of 80 adult men, aged 36-55 years, participated in this study. The group comprised 40 fertile control men and 40 men with idiopathic infertility who received antioxidant treatment. Among them, 15 men were younger than 36 years and 65 men were older than 36 years. All the infertile men had been married for at least five years and had no children. The study samples were collected from an infertility clinic at Kirkuk Teaching Hospital and private clinics. Each patient received glutathione supplementation once a day for five months, starting oral antioxidant therapy in July and continuing until December 2023, along with garlic taken twice daily with food. Initially, there were slight but significant differences observed in FSH and LH levels between the control group and infertility patients before treatment, while testosterone levels were significantly lower in the infertility group. However, after five months of treatment, there was a significant increase in FSH, LH, and testosterone levels in the idiopathic infertility group compared to the control group. The research indicated a significant increase in seminal plasma glutathione (GSH) and glutathione peroxidase (GPx) and a significant reduction in seminal plasma malondialdehyde (MDA). These changes led to a significant increase in the sperm count of idiopathic infertility men after five months of treatment compared to the control group. Furthermore, FSH levels significantly increased after two months of treatment, with a corresponding increase in serum GSH. Thus, the administration of glutathione with garlic significantly reduced serum MDA and significantly increased serum FSH, total testosterone, and the count of motile sperm in idiopathic infertility men. Key Words: L-Glutathione250MG , Garlic ,idiopathic infertility men ,sperm count ,total testosterone

Glutathione in HIV-Associated Neurocognitive Disorders.

A large portion of patients with Human Immunodeficiency Virus (HIV) have neurologic sequelae. Those with better-controlled HIV via antiretroviral therapies generally have less severe neurologic symptoms. However, for many patients, antiretrovirals do not adequately resolve symptoms. Since much of the pathogenesis of HIV/AIDS (Autoimmune Deficiency Syndrome) involves oxidative stress either directly, through viral interaction, or indirectly, through inflammatory mechanisms, we have reviewed relevant trials of glutathione supplementation in each of the HIV-associated neurocognitive diseases and have found disease-specific results. For diseases for which trials have not been completed, predicted responses to glutathione supplementation are made based on relevant mechanisms seen in the literature. It is not sufficient to conclude that all HIV-associated neurocognitive disorders (HAND) will benefit from the antioxidant effects of glutathione supplementation. The potential effects of glutathione supplementation in patients with HAND are likely to differ based on the specific HIV-associated neurocognitive disease.

Glutathione Supplementation Prevents Neonatal Parenteral Nutrition-Induced Short- and Long-Term Epigenetic and Transcriptional Disruptions of Hepatic H2O2 Metabolism in Guinea Pigs.

The parenteral nutrition (PN) received by premature newborns is contaminated with peroxides that induce global DNA hypermethylation via oxidative stress. Exposure to peroxides could be an important factor in the induction of chronic diseases such as those observed in adults who were born preterm. As endogenous H2O2 is a major regulator of glucose-lipid metabolism, our hypothesis was that early exposure to PN induces permanent epigenetic changes in H2O2 metabolism. Three-day-old guinea pigs were fed orally (ON), PN or glutathione-enriched PN (PN+GSSG). GSSG promotes endogenous peroxide detoxification. After 4 days, half the animals were sacrificed, and the other half were fed ON until 16 weeks of age. The liver was harvested. DNA methylation and mRNA levels were determined for the SOD2, GPx1, GCLC, GSase, Nrf2 and Keap1 genes. PN induced GPx1 hypermethylation and decreased GPx1, GCLC and GSase mRNA. These findings were not observed in PN+GSSG. PN+GSSG induced Nrf2 hypomethylation and increased Nrf2 and SOD2 mRNA. These observations were independent of age. In conclusion, in neonatal guinea pigs, PN induces epigenetic changes, affecting the expression of H2O2 metabolism genes. These changes persist for at least 15 weeks after PN. This disruption may signify a permanent reduction in the capacity to detoxify peroxides.

Evaluation of Glutathione in Spike Protein of SARS-CoV-2 Induced Immunothrombosis and Cytokine Dysregulation.

Thrombotic microangiopathy has been identified as a dominant mechanism for increased mortality and morbidity in coronavirus disease 2019 (COVID-19). In the context of severe COVID-19, patients may develop immunothrombosis within the microvasculature of the lungs, which contributes to the development of acute respiratory distress syndrome (ARDS), a leading cause of death in the disease. Immunothrombosis is thought to be mediated in part by increased levels of cytokines, fibrin clot formation, and oxidative stress. Glutathione (GSH), a well-known antioxidant molecule, may have therapeutic effects in countering this pathway of immunothrombosis as decreased levels of (GSH) have been associated with increased viral replication, cytokine levels, and thrombosis, suggesting that glutathione supplementation may be therapeutic for COVID-19. GSH supplementation has never been explored as a means of treating COVID-19. This study investigated the effectiveness of liposomal glutathione (GSH) as an adjunctive therapy for peripheral blood mononuclear cells (PBMC) treated with SARS CoV-2 spike protein. Upon the addition of GSH to cell cultures, cytokine levels, fibrin clot formation, oxidative stress, and intracellular GSH levels were measured. The addition of liposomal-GSH to PBMCs caused a statistically significant decrease in cytokine levels, fibrin clot formation, and oxidative stress. The addition of L-GSH to spike protein and untreated PBMCs increased total intracellular GSH, decreased IL-6, TGF-beta, and TNF-alpha levels, decreased oxidative stress, as demonstrated through MDA, and decreased fibrin clot formation, as detected by fluorescence microscopy. These findings demonstrate that L-GSH supplementation within a spike protein-treated PBMC cell culture model reduces these factors, suggesting that GSH supplementation should be explored as a means of reducing mediators of immunothrombosis in COVID-19.

Glutathione supplementation improves fat graft survival by inhibiting ferroptosis via the SLC7A11/GPX4 axis

BackgroundAutologous fat grafting is hampered by unpredictable graft survival, which is potentially regulated by ferroptosis. Glutathione (GSH), a powerful antioxidant used in tissue preservation, has ferroptosis-regulating activity; however, its effects on fat grafts are unclear. This study investigated the effects and mechanisms of GSH in fat graft survival.MethodsHuman lipoaspirates were transplanted subcutaneously into the backs of normal saline-treated (control) or GSH-treated nude mice. Graft survival was evaluated by magnetic resonance imaging and histology. RNA sequencing was performed to identify differentially expressed genes and enriched pathways. GSH activity was evaluated in vitro using an oxygen and glucose deprivation (OGD) model of adipose-derived stem cells.ResultsCompared with control group, GSH induced better outcomes, including superior graft retention, appearance, and histological structures. RNA sequencing suggested enhanced negative regulation of ferroptosis in the GSH-treated grafts, which showed reduced lipid peroxides, better mitochondrial ultrastructure, and SLC7A11/GPX4 axis activation. In vitro, OGD-induced ferroptosis was ameliorated by GSH, which restored cell proliferation, reduced oxidative stress, and upregulated ferroptosis defense factors.ConclusionsOur study confirms that ferroptosis participates in regulating fat graft survival and that GSH exerts a protective effect by inhibiting ferroptosis. GSH-assisted lipotransfer is a promising therapeutic strategy for future clinical application.

Metabolic perturbation studies using a Nash Equilibrium model of liver machine perfusion: modeling oxidative stress and effect of glutathione supplementation

The current clinical standard of Static Cold Storage (SCS) which involves preservation on ice (about +4°C) in a hypoxic state limits storage to a few hours for metabolically active tissues such as the liver and the heart. This period of hypoxia during can generate superoxide and other free radicals from purine metabolism, a well-established component of ischemia/reperfusion injury (IRI). Machine perfusion is at the cutting edge of organ preservation, which provides a functional, oxygenated preservation modality that can avoid/attenuate IRI. In clinical application, perfusion usually follows a period of SCS. This presentation of oxygen following hypoxia can lead to superoxide and hydrogen peroxide generation, but machine perfusion also allows manipulation of the temperature profiles and supply of antioxidant treatments, which could be used to minimize such issues. However, metabolomic data is difficult to gather, and there are currently no mathematical models present to allow rational design of experiments or guide clinical practice. In this article, the effects of a gradual warming temperature policy and glutathione supplementation to minimize oxidative stress are studied. An optimal gradual warming temperature policy for mid-thermic machine perfusion of a liver metabolic model is determined using a combination of Nash Equilibrium and Monte Carlo optimization. Using this optimal gradual warming temperature policy, minimum GSH requirements to maintain hydrogen peroxide concentrations in the normal region are calculated using a different Monte Carlo optimization methodology. In addition, the dynamic behavior of key metabolites and cofactors are determined. Results show that the minimum GSH requirement increases and that the ratio of GSH/GSSG decreases with increasing hydrogen peroxide concentration. In addition, at high concentrations of hydrogen peroxide it is shown that cytochrome C undergoes dysfunction leading to a decrease in useful oxygen consumption and ATP synthesis from the electron transport chain and an overall reduction in the energy charge for the liver cells.

The Quality of KUB Rooster Sperm During Cryopreservation in Extender with Genistein and Glutathione Supplementation

The Quality of KUB Rooster Sperm During Cryopreservation in Extender with Genistein and Glutathione Supplementation

Antioxidant Glutathione Supplementation in Semen Extenders and its Effect on the Quality of Cryopreserved Bull Sperm: A Meta-Analysis

Antioxidant Glutathione Supplementation in Semen Extenders and its Effect on the Quality of Cryopreserved Bull Sperm: A Meta-Analysis

Preparation and characterization of glutathione loaded polyvinyl alcohol electrospun nanofibers

Reduced glutathione, or L-glutathione, is a tripeptide protein that occurs naturally in almost all cells of the human body. It is an antioxidant and plays a significant role in neutralizing oxidative stress. Oxidative stress is responsible for promoting many diseases and abnormalities in the body. This antioxidant decreases with time, and resulting in a number of disorders. To overcome these issues, experts recommend taking glutathione supplements. This study was aimed to design glutathione-loaded polyvinyl alcohol nanofibers, considering the properties of nanofibers that could be used as glutathione supplements to improve the deficiency of glutathione in the human body. With the electrospinning technique, poly (vinyl alcohol) loaded glutathione nanofibers were designed. The prepared nanofibers were characterized using Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), and Ultraviolet-Visible Spectroscopy (UV–Vis) techniques. The antioxidant activity of the nanofibers was also determined; the activity indicated the eradication of free radicals.

Glutathione is required for growth and cadmium tolerance in the amphibian chytrid fungus, Batrachochytrium dendrobatidis

Batrachochytrium dendrobatidis (Bd) is a lethal amphibian pathogen, partly due to its ability to evade the immune system of susceptible frog species. In many pathogenic fungi, the antioxidant glutathione is a virulence factor that helps neutralise oxidative stressors generated from host immune cells, as well as other environmental stressors such as heavy metals. The role of glutathione in stress tolerance in Bd has not been investigated. Here, we examine the changes in the glutathione pool after stress exposure and quantify the effect of glutathione depletion on cell growth and stress tolerance. Depletion of glutathione repressed growth and release of zoospores, suggesting that glutathione is essential for life cycle completion in Bd. Supplementation with <2 mM exogenous glutathione accelerated zoospore development, but concentrations >2 mM were strongly inhibitory to Bd cells. While hydrogen peroxide exposure lowered the total cellular glutathione levels by 42 %, glutathione depletion did not increase the sensitivity to hydrogen peroxide. Exposure to cadmium increased total cellular glutathione levels by 93 %. Glutathione-depleted cells were more sensitive to cadmium, and this effect was attenuated by glutathione supplementation, suggesting that glutathione plays an important role in cadmium tolerance. The effects of heat and salt were exacerbated by the addition of exogenous glutathione. The impact of glutathione levels on Bd stress sensitivity may help explain differences in host susceptibility to chytridiomycosis and may provide opportunities for synergistic therapeutics.

Evaluation of the antioxidant and anti-inflammatory effect of sublingual glutathione on COPD patients.

Glutathione (GSH) is a potent antioxidant and anti-inflammatory, proven effective in reducing treatment duration, prescribed doses, and hospitalization for several diseases. This study assessed the therapeutic response of chronic obstructive pulmonary disease (COPD) patients by measuring oxidative superoxide dismutase (SOD3), glutathione peroxidase 1 (GPX1), and inflammatory biomarkers such as tumor necrosis factor-alpha (TNF-α) and Interleukin-8 (IL-8) after sublingual administration of glutathione supplements. A cohort of 50 COPD individuals was involved and divided into two groups of 25 each. The first group received conventional therapy involving the administration of formoterol fumarate (12 µg inhaler) twice daily. The second group received the conventional treatment alongside sublingual glutathione (300 mg twice daily) for two months. The levels of serum IL-8, TNF-α, SOD3, and GPX1 were assessed before therapy, as well as at one and two months after treatment, in both cohorts. Both groups exhibited a notable reduction in the inflammatory mediators IL-8 and TNF-α when compared to their respective pre-treatment levels (P value <0.05). However, it is worth noting that the observed difference between the groups was not statistically significant (P value >0.05). The levels of SOD3 and GPX1 exhibited a substantial rise in both groups; however, they were found to be greater in group 2 compared to group 1 (P value >0.05). The administration of glutathione resulted in enhanced levels of antioxidant biomarkers among individuals diagnosed with COPD, accompanied by a minor and statistically insignificant decrease in the levels of the anti-inflammatory mediators IL-8 and TNF-alpha.

Vitamin C and glutathione supplementation: a review of their additive effects on exercise performance.

This review aimed to investigate the effects of vitamin C and glutathione supplementation on exercise performance. We conducted a literature search across the PubMed, Google Scholar, and Web of Science databases using the keywords vitamin C, glutathione, antioxidants, exercise, and oxidative stress. The effects of vitamin C supplementation on exercise performance and oxidative stress levels are inconsistent. Glutathione, with its diverse forms of supplementation and methods, presents mixed outcomes. Vitamin C and glutathione have deeply interconnected antioxidant functions and are mutually essential to each other. Research investigating the combined intake of these two substances, which are intricately linked biochemically, and their effects on exercise performance remain largely unexplored. Studies on the effects of vitamin C and glutathione intake on exercise have been conducted using diverse approaches; however, the results have not been consistent. Although an additive effect is anticipated with the combined intake of vitamin C and glutathione, research on this topic is currently insufficient, and further studies are required.

Dietary glutathione supplementation attenuates oxidative stress and improves intestinal barrier in diquat-treated weaned piglets

ABSTRACT The aim of this study was to investigate the protective effects of glutathione (GSH) against oxidative stress and intestinal barrier disruption caused by diquat (an oxidative stress inducer) in weaned piglets. Twenty-four piglets were randomly assigned to four treatments with six pigs per treatment for an 18-d trial. Treatments were basal diet, basal diet + diquat challenge, 50 mg/kg GSH diets + diquat challenge and 100 mg/kg GSH diets + diquat challenge. On day 15, piglets in basal diet group and diquat-challenged groups were intraperitoneally injected with sterile saline and diquat at 10 mg/kg body weight, respectively. The results showed that GSH supplementation improved growth performance of diquat-injected piglets from days 15 to 18 (p < 0.05), especially at a dose of 100 mg/kg GSH. Meanwhile, diquat also caused oxidative stress and intestinal barrier damage in piglets. However, GSH supplementation enhanced the antioxidant capacity of serum and jejunum, as evidenced by the increase in GSH content and total superoxide dismutase activities and the decrease in 8-hydroxy-2’-deoxyguanosine concentrations (p < 0.05). GSH also up-regulated the mRNA expressions of intestinal tight junction protein (zonula occludens 1, ZO1; occludin, OCLN; claudin-1, CLDN1) and mitochondrial biogenesis and function (peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, PGC1α; mitochondrial transcription factor A, TFAM; cytochrome c, CYCS), compared with diquat-challenged piglets in basal diet (p < 0.05). Thus, the study demonstrates that GSH protects piglets from oxidative stress caused by diquat and 100 mg/kg GSH has a better protective role.

The role of high dose vitamin d and glutathione supplementation in COVID-19 treatment: A case series

COVID-19 has been affecting millions of people worldwide and becoming a global public health burden. Therefore, exploring treatment options is essential to help flatten the curve and reduce hospitalization time. This is a case series of ten COVID-19 patients in Jakarta and Tangerang, Indonesia, who received a high dose of vitamin D and glutathione supplementation daily. Within 5-7 days of treatment, all patients were confirmed COVID-19 negative. To date, this is the first report from Indonesia describing the potential benefit of supplementing vitamin D and glutathione concurrently in improving clinical conditions and expediting the recovery time of COVID-19 patients.