GSH In Group Research Articles

Protective effect of reduced glutathione on acute kidney injury in lung cancer patients treated with cisplatin: a retrospective cohort study

Background Cisplatin is a common cause of acute kidney injury (AKI) during chemotherapy for lung cancer, and the nephrotoxicity limits its clinical use. Reduced glutathione (GSH) is a major component of the cellular antioxidant defense system and performs important physiological functions. The aim of this study was to analyze the protective effect of GSH on AKI in lung cancer patients treated with cisplatin. Methods The clinical data were retrospectively collected from lung cancer patients treated with cisplatin at our hospital between 1 January and 31 December 2019. The patients were divided into AKI group and non-AKI group based on whether AKI occurred, and into GSH group and non-GSH group based on whether GSH was used. Univariate and multivariate logistic regressions were used to analyze the risk factors for AKI. Results A total of 1372 lung cancer patients treated with cisplatin were enrolled. Of these patients, 231 patients (16.8%) developed AKI. The incidence of AKI was lower in the GSH group compared with the non-GSH group (10.6% vs. 18%, p = 0.009). Multivariate logistic regression analysis indicated that older age (OR = 1.045, 95% CI 1.025–1.065, p < 0.001), anemia (OR = 2.436, 95% CI 1.800–3.298, p < 0.001), higher SUA levels (OR = 1.002, 95% CI 1.000–1.004, p = 0.012), higher total amount of cisplatin per cycle (OR = 1.015, 95% CI 1.004–1.025, p = 0.005), and combination with paclitaxel (OR = 2.099, 95% CI 1.435–3.070, p < 0.001) were independent risk factors for AKI in lung cancer patients treated with cisplatin, whereas GSH (OR = 0.573, 95% CI 0.353–0.931, p = 0.025) and mannitol (OR = 0.229, 95% CI 0.055–0.963, p = 0.044) reduced the risk of AKI. Conclusion GSH was an independent protective factor against AKI in lung cancer patients treated with cisplatin and could be considered for clinical use in these patients to better protect renal function.

Exogenous glutathione (GSH/GSSG) promoted the synthesis of patchoulol and pogostone, main active components of Pogostemon cablin (Patchouli)

Glutathione redox pair (GSH/GSSG) is the main characterizing substance that regulates the redox balance in cells and affects several physiological processes, such as plant metabolism, antioxidants, and detoxification. Pogostemon cablin was treated with different concentrations of reduced glutathione (GSH) and oxidized glutathione (GSSG), and it was found that 2 mM GSH and 4 mM GSSG treatments promoted the synthesis of patchoulol and pogostone. A total of 6620 significant differentially expressed gene were identified by transcriptome analysis. KEGG analysis showed that DEGs were mainly enriched in metabolic pathways, secondary metabolite biosynthesis, carbon metabolism, and phytohormone signaling pathways; 388 DEGs in the 2 mM GSH (11d) group, and 254 DEGs in the 4 mM GSSG (11d) group, were related to the biosynthesis of secondary metabolites. Further analysis by Gene Set Enrichment Analysis (GSEA) revealed that there were 139 and 83 DEGs associated with terpene synthesis between the two treatment groups, respectively, and the expression of key genes in the synthesis pathway (11 HMGR, 4 DXR, 2 GPPS, and 8 PTS) was up-regulated, which may be the result of transcription factors regulating their expression. The present study preliminarily showed that glutathione redox pair induced the expression of genes related to the terpene biosynthesis pathway, thereby promoting the biosynthesis of patchoulol and pogostone, which provides a reference basis for the technique of regulating and controlling the content of medicinal constituents of patchouli.

The dithiol mechanism of class I glutaredoxins promotes specificity for glutathione as a reducing agent

Class I glutaredoxins reversibly reduce glutathione- and nonglutathione disulfides with the help of reduced glutathione (GSH) using either a monothiol mechanism or a dithiol mechanism. The monothiol mechanism exclusively involves a single glutathionylated active-site cysteinyl residue, whereas the dithiol mechanism requires the additional formation of an intramolecular disulfide bond between the active-site cysteinyl residue and a resolving cysteinyl residue. While the oxidation of glutaredoxins by glutathione disulfide substrates has been extensively characterized, the enzyme-substrate interactions for the reduction of S-glutathionylated glutaredoxins or intramolecular glutaredoxin disulfides are still poorly characterized. Here we compared the thiol-specificity for the reduction of S-glutathionylated glutaredoxins and the intramolecular glutaredoxin disulfide. We show that S-glutathionylated glutaredoxins rapidly react with a plethora of thiols and that the 2nd glutathione-interaction site of class I glutaredoxins lacks specificity for GSH as a reducing agent. In contrast, the slower reduction of the partially strained intramolecular glutaredoxin disulfide involves specific interactions with both carboxylate groups of GSH at the 1st glutathione-interaction site. Thus, the dithiol mechanism of class I glutaredoxins promotes specificity for GSH as a reducing agent, which might explain the prevalence of dithiol glutaredoxins in pro- and eukaryotes.

A robust ultra-performance liquid chromatography-tandem mass spectrometry method for simultaneous determination of 10 components in glutathione cycle.

Glutathione (GSH) is an important antioxidant that is generated and degraded via the GSH cycle. Quantification of the main components in the GSH cycle is necessary to evaluate the process of GSH. In this study, a robust ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of 10 components (GSH; γ-glutamylcysteine; cysteinyl-glycine; n-acetylcysteine; homocysteine; cysteine; cystine; methionine; glutamate; pyroglutamic acid) in GSH cycle was developed. The approach was optimized in terms of derivative, chromatographic, and spectrometric conditions as well as sample preparation. The unstable thiol groups of GSH, γ-glutamylcysteine, cysteinyl-glycine, n-acetylcysteine, cysteine, and homocysteine were derivatized by n-ethylmaleimide. The derivatized and underivatized analytes were separated on an amino column with gradient elution. The method was further validated in terms of selectivity (no interference), linearity (R2>0.99), precision (% relative standard deviation [RSD%] range from 0.57 to 10.33), accuracy (% relative error [RE%] range from -3.42 to 10.92), stability (RSD% < 5.68, RE% range from -2.54 to 4.40), recovery (RSD% range from 1.87 to 7.87) and matrix effect (RSD% < 5.42). The validated method was applied to compare the components in the GSH cycle between normal and oxidative stress cells, which would be helpful in clarifying the effect of oxidative stress on the GSH cycle.

Biocompatibility FeOOH QD@ATP-BODIPY nanocomposite for glutathione detection and intracellular imaging

Monitoring of glutathione has attracted considerable attention owing to its biological and clinical significance. An eco-friendly, economic, simple, biocompatible probe with excellent sensitivity and selectivity is very important. Herein, FeOOH QD@ATP-BODIPY nanocomposite was fabricated from one-step synthesized FeOOH quantum dots (FeOOH QD) and commercial boron-dipyrromethene-conjugated adenosine 5′-triphosphate (ATP-BODIPY) for glutathione (GSH) sensing in solutions and living cells. Three fascinate merits of FeOOH QD were confirmed: (a) as fluorescence quencher for ATP-BODIPY, (b) as selective recognizer of GSH and (c) with carrier effects and membrane permeability. The construction and response mechanism of the nanocomposite was based on the competitive coordination chemistry and redox reaction of FeOOH QD between GSH and phosphate group of ATP-BODIPY. Under the optimal conditions, the detection limit for GSH was as low as 68.8 nM. Excellent linear range of 0.2–400 μM was obtained. Furthermore, the chemical response of the nanocomposite exhibits high selectivity toward GSH over other electrolytes and biomolecules. It was successfully applied for GSH determination in human serum samples. The MTT assay exhibited FeOOH QD@ATP-BODIPY nanocomposite own good biocompatibility. FeOOH QD@ATP-BODIPY respond to GSH in living cells in situ was also proved via fluorescence imaging. These suggested that the FeOOH QD@ATP-BODIPY nanocomposite had potential application in biological and clinical applications.

In vivo chronic exposure to inorganic mercury worsens hypercholesterolemia, oxidative stress and atherosclerosis in the LDL receptor knockout mice

Heavy metal exposure leads to multiple system dysfunctions. The mechanisms are likely multifactorial and involve inflammation and oxidative stress. The aim of this study was to evaluate markers and risk factors for atherosclerosis in the LDL receptor knockout mouse model chronically exposed to inorganic mercury (Hg) in the drinking water. Results revealed that Hg exposed mice present increased plasma levels of cholesterol, without alterations in glucose. As a major source and target of oxidants, we evaluated mitochondrial function. We found that liver mitochondria from Hg treated mice show worse respiratory control, lower oxidative phosphorylation efficiency and increased H2O2 release. In addition, Hg induced mitochondrial membrane permeability transition. Erythrocytes from Hg treated mice showed a 50% reduction in their ability to take up oxygen, lower levels of reduced glutathione (GSH) and of antioxidant enzymes (SOD, catalase and GPx). The Hg treatment disturbed immune system cells counting and function. While lymphocytes were reduced, monocytes, eosinophils and neutrophils were increased. Peritoneal macrophages from Hg treated mice showed increased phagocytic activity. Hg exposed mice tissues present metal impregnation and parenchymal architecture alterations. In agreement, increased systemic markers of liver and kidney dysfunction were observed. Plasma, liver and kidney oxidative damage indicators (MDA and carbonyl) were increased while GSH and thiol groups were diminished by Hg exposure. Importantly, atherosclerotic lesion size in the aorta root of Hg exposed mice were larger than in controls. In conclusion, in vivo chronic exposure to Hg worsens the hypercholesterolemia, impairs mitochondrial bioenergetics and redox function, alters immune cells profile and function, causes several tissues oxidative damage and accelerates atherosclerosis development.

Diet with optimal glutathione supplement improves growth, nonspecific immunity, intestinal microbiota, and antioxidant ability in Micropterus salmoides.

In this study, Micropterus salmoides were fed with dietary glutathione (GSH, 0, 100, 300, and 500 mg/kg) for 56 days to investigate its effects on growth performance, serum nonspecific immunity, liver antioxidant capacity, tissue morphology, and intestinal microbiota. The results showed that the survival rate, weight gain rate, and specific growth rate and condition factor increased, whereas the feed conversion ratio, hepato-somatic index, and viscerosomatic index decreased in the GSH groups. Compared with the control group, the serum total protein content significantly increased, whereas the triglyceride and total cholesterol significantly decreased in the 300-mg/kg dietary GSH group. The activities of lysozyme, alkaline phosphatase, and acid phosphatase were significantly higher in GSH-supplemented groups, peaking at 300-mg/kg GSH. GSH supplementation significantly increased total antioxidant capacity and decreased malondialdehyde content, with the most pronounced effects at 300-mg/kg GSH. Further antioxidant indicators showed that a dietary supplement of 300-mg/kg GSH significantly increased the activities of superoxide dismutase, glutathione transferase, endogenous glutathione, glutathione reductase, and catalase. At 300-mg/kg GSH, the liver exhibited improved characteristics with alleviated vacuolation and hepatocyte nuclear shift, and intestine showed enhanced structure with increased villus height and intestinal wall thickness. Additionally, a 300-mg/kg GSH supplementation improved the diversity of intestinal microbiota, increased the abundance of probiotics such as Bacillus, and inhibited the development of pathogenic bacteria such as Plesiomonas. Overall, the results suggest that the effect of GSH addition on improving growth performance, nonspecific immunity, antioxidant capacity, and intestinal microbiota of M. salmoides is best in the 300-mg/kg addition group. Based on second-degree polynomial regression analysis of weight gain, the optimum requirement of dietary GSH in M. salmoides is a 336.84-mg/kg diet.

Potential treatment of glutathione in bullfrogs with abnormal hepatic lipid metabolism revealed by hepatic lipid metabolism and serum metabolomics analysis.

With the continuous growth of bullfrog supply, it has become an important aquaculture species. Due to the lack of actionable industry standards and regulation, the misuse of anti-disease drugs and abnormal liver lipid metabolism in bullfrogs have become a major obstacle to the development of bullfrog aquaculture industry. Glutathione is a natural tripeptide that can be synthesized intracellularly, and its physiological functions mainly include the treatment of liver diseases, antioxidant, detoxification, anti-tumor, enhancement of immunity, and delaying aging. In this study, the therapeutic effect of glutathione on bullfrogs with abnormal liver lipid metabolism was revealed from hepatic lipid metabolism and serum metabolomics analysis. The survival rate, liver histomorphology, serum antioxidant enzyme activity, liver lipase activity and serum metabolomics, liver metabolomics were studied and analyzed by feeding the bullfrogs with abnormal lipid metabolism with glutathione for 20 days in the NC, FI and GSH groups. The results of the study showed that glutathione was able to repair the liver and improve the survival rate of bullfrogs with abnormal lipid metabolism; the activity of serum SOD enzymes was significantly increased; the activities of ACP and AKP were significantly decreased; the activities of HDL-C and T-CHO were significantly increased; and the activities of LDL-C, TBA, and TG were significantly decreased in the liver; the contents of metabolites, such as PC, PS, and PE were significantly up-regulated, and the levels of up-regulated Autophagy - other, Necroptosis and ErbB signaling pathway, and down-regulated Sphingolipid metabolism, D-Amino acid metabolism metabolic pathway, to some extent The metabolic pathways of Sphingolipid metabolism and D-Amino acid metabolism were down-regulated to alleviate the disorders of glycerophospholipid and amino acid metabolism to a certain extent, thus alleviating the abnormalities of liver lipid metabolism. The results showed that glutathione could effectively treat the liver lipid metabolism disorder of bullfrogs, promote the growth and development of bullfrogs, repair the liver function, reduce the inflammation, and promote the healthy and green development of bullfrog industry.

Exogenous glutathione reverses meropenem resistance in carbapenem-resistant Klebsiella pneumoniae.

Background: The rate of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has been increasing rapidly worldwide and, poses a significant risk to human health. Effective methods are urgently needed to address treatment failures related to antibiotic resistance. Recent research has reported that some drugs in combination with antibiotics have displayed synergistic killing of resistant bacteria. Here, we investigated whether glutathione (GSH) can synergize with meropenem, and enhance its effectiveness against CRKP. Methods: Synergistic activity was assessed by checkerboard and time-killing assays. The mechanism of these combinations was assessed by total ROS and membrane permeability assays. The bacterial metabolites were assessed by LC‒MS/MS. Results: The FICIs of GSH and meropenem were approximately 0.5 and the combined treatment with GSH and meropenem resulted in a more than 2log10CFU/mL reduction in bacteria compared to the individual treatments. These findings indicated the synergistic effect of the two drugs. Moreover, the meropenem MIC of CRKP was reduced to less than 4mg/L when combined with 6mg/mL GSH, indicating that GSH could significantly reverse resistance to meropenem in bacteria. The production of ROS in bacteria was determined by flow cytometry. After adding GSH, the ROS in the GSH group and the combined group was significantly higher than that in the control and meropenem groups, but there was no significant difference between the combined and GSH groups. The metabolic disturbance caused by GSH alone and in combination with meropenem was significant intracellularly and extracellularly, especially in terms of glycerophospholipid metabolism, indicating that the synergistic effect of the combined use of GSH and meropenem was relevant to glycerophospholipid metabolism. In addition, we measured the cell membrane permeability. The cell membrane permeability of the combination group was significantly higher than that of the blank control or monotreatment groups. This confirmed that the GSH can serve as a meropenem enhancers by disturbing glycerophospholipid metabolism and increasing cell membrane permeability. Conclusion: GSH and meropenem display a synergistic effect, wherein GSH increases the sensitivity of CRKP to meropenem. The synergy and susceptibility effects are thought to related to the increased membrane permeability resulting from the perturbations in glycerophospholipid metabolism, presenting a novel avenue for CRKP treatment.

The kinetics of glutathione in the gastrointestinal tract of weaned piglets supplemented with different doses of dietary reduced glutathione.

This study aimed to investigate the kinetics of dietary GSH in the gastrointestinal tract and the effect of GSH on the intestinal redox status of weaned piglets. Forty-eight piglets with an average age of 26 days and an average body weight of 7.7 kg were used in this study. The piglets were divided into three treatment groups including the control group with a basal diet (CON) and two GSH groups with a basal diet supplemented with 0.1% GSH (LGSH) and 1.0% GSH (HGSH), respectively. The basal diet did not contain any GSH. The experiment lasted for 14 days, with eight animals sampled from each group on d5 and 14. The parts of 0-5%, 5-75%, and 75-100% of the length of the small intestine were assigned to SI1, SI2, and SI3. The results showed that GSH almost completely disappeared from the digesta at SI2. However, no difference in the GSH level in mucosa, liver, and blood erythrocytes was found. The level of cysteine (CYS) in SI1 digesta was significantly higher in HGSH than CON and LGSH on d14, and similar findings were observed for cystine (CYSS) in SI3 digesta on d5. The CYSS level in HGSH was also significantly higher than LGSH in the stomach on d14, while no CYS or CYSS was detected in the stomach for control animals, indicating the breakdown of GSH to CYS already occurred in the stomach. Irrespective of the dietary treatment, the CYS level on d14 and the CYSS level on d5 and 14 were increased when moving more distally into the gastrointestinal tract. Furthermore, the mucosal CYS level was significantly increased at SI1 in the LGSH and HGSH group compared with CON on d5. Glutathione disulfide (GSSG) was recovered in the diets and digesta from the LGSH and HGSH group, which could demonstrate the auto-oxidation of GSH. It is, therefore, concluded that GSH supplementation could not increase the small intestinal mucosal GSH level of weaned piglets, and this could potentially relate to the kinetics of GSH in the digestive tract, where GSH seemed to be prone to the breakdown to CYS and CYSS and the auto-oxidation to GSSG.

Effect of In Vitro Addition of Melatonin and Glutathione on Seminal Parameters of Rams in Diluted Semen and after Thawing.

The present study aimed to evaluate the effects of melatonin (MLT), glutathione (GSH), and their combination on ram semen quality after thawing. During eight weekly sessions, semen from three Merino rams was pooled, diluted with an egg-yolk-based semen extender, and divided into four groups: control, 1 mM MLT, 5 mM GSH, and 1 mM MLT + 5 mM GSH. Diluted semen was evaluated before and after the freezing process. The supplementation of diluted semen with GSH at 5 mM had a deleterious effect on total motility progressive (TPM), curvilinear velocity (VCL), straight-line velocity (VSL), average-path velocity (VAP), linearity (LIN), and straightness (STR) and increased slow spermatozoa (%). MLT at 1 mM also had a negative effect on TPM, VSL, and STR in diluted semen. In thawed semen, 1 mM MLT increased the TPM compared with the control group. VSL was lower in the 5 mM GSH group than in the 1 mM MLT group. Additionally, the combination of both antioxidants attenuated the negative effect of 5 mM GSH on TPM, VSL, and BCF. These results indicate that 5 mM GSH impairs or does not improve sperm kinetic parameters in either diluted or thawed semen. They also suggest that MLT combined with GSH plays a protective role against these effects.

Oxiditive Stress biomarkers levels in blood sample of Iraqi Breast cancer patients

Background: Breast cancer is a malignant tumor arising from epithelial cells of glandular lacteferons ducts or terminal ductilobular unit (TDLM) of the breast which is affected by the oxidative stress and the defensive mechanisms against it. Objective: to reveal the correlation between the levels of superoxide dismutase (CuZn SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR), reduced glutathione (GSH) and sulfhydryl groups (SH) with breast cancer with/without metast. Methods: A case control study was performed on 30 female patients with metastasized breast cancer, 30 female patients with non- metastasized breast cancer and 30 female patients with benign breast tumor. All patients were recruited from Al-Karama teaching hospital at Wasit city in Iraq, for the period from October 2021 to February 2022. Results: The levels of GSH-PX, GR, GSH, and sulfhydral groups were significantly reduced in breast cancer patients in comparison with healthy controls whereas SOD levels were upregulated in breast cancer patients in comparison with healthy controls subjected to the current study. Conclusions: It is concluded that the activities of superoxide dismutase (CuZn SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR), as well as concentrations of reduced glutathione (GSH) and sulfhydryl groups (SH) have a significant impact on the pathogenisis and progression of breast cancer.

Glutathione and selenium nanoparticles have a synergistic protective effect during cryopreservation of bull semen.

In the present study, the synergistic protective effect of co-supplementation of glutathione (GSH) with selenium nanoparticles (SeNPs) on the cryopreservation efficiency of bull semen was analyzed. After collection, the ejaculates of Holstein bulls were subsequently diluted with a Tris extender buffer supplemented with different concentrations of SeNPs (0, 1, 2, and 4 μg/ml), followed by semen equilibration at 4°C and assessment of sperm viability and motility. Subsequently, the ejaculates of Holstein bulls were pooled, split into four equal groups, and diluted with a Tris extender buffer supplemented with basic extender (negative control group, NC group), 2 μg/ml SeNPs (SeNPs group), 4 mM GSH (GSH group), and 4 mM GSH plus 2 μg/ml SeNPs (GSH + SeNPs group). After cryopreservation, motility, viability, mitochondrial activity, plasma membrane integrity, acrosome integrity, concentration of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT), and ability of frozen-thawed sperm cells to support in vitro embryonic development were evaluated. No side effect of SeNPs concentrations applied in the current study on the motility and viability of equilibrated bull spermatozoa was found. Meanwhile, supplementation of SeNPs significantly promoted the motility and viability of equilibrated bull spermatozoa. Furthermore, the co-supplementation of GSH with SeNPs effectively protected bull spermatozoa from cryoinjury as expressed by promoting semen motility, viability, mitochondrial activity, plasma membrane integrity, and acrosome integrity. Finally, the enhanced antioxidant capacity and embryonic development potential in the frozen-thawed bull spermatozoa cryopreserved by co-supplementation of GSH with SeNPs further confirmed the synergistic protective effect of co-supplementation of GSH with SeNPs on the cryopreservation of bull semen.

Effects of glutathione on mitochondrial DNA and antioxidant enzyme activities in Drosophila melanogaster

The free radical theory in aging assumes that the accumulation of macromolecular damage induced by toxic reactive oxygen species plays a central role in the aging process. The intake of nutritional antioxidants can prevent this damage by neutralizing reactive oxygen derivatives. Glutathione (GSH; en-L-Glutamyl-L-cysteinyl glycine) is the lowest molecular weight thiol in the cells and as a cofactor of many enzymes and a potent antioxidant plays an important role in maintaining normal cell functions by destroying toxic oxygen radicals. In this study, the effects of GSH on SOD, GST and catalase enzymes and mtDNA damage were investigated at various time intervals by giving reduced glutathione to Drosophila. It was observed that 3-week GSH administration did not have a statistically significant effect on SOD and GST activities whereas GSH application decreased the catalase enzyme activities significantly. Although the decrease in antioxidant capacity with age was observed in SOD and catalase enzymes, such a situation was not observed in GST enzyme activities. There was no statistically significant difference between the control and GSH groups in mtDNA copy number values, while in the GSH group, oxidative mtDNA damage was high. These results may be due to the prooxidant effect of GSH at the dose used in this study.

Depletion of glutathione induced apoptosis and oxidative stress via the activation of TRPM2 channels in the microglia cells with Alzheimer’ disease model

Alzheimer’s disease is a common neurodegenerative disease. Microglia induces oxidative stress in the brain for engulfing bacteria and viruses. The accumulating data indicate that oxidative stress and apoptosis are two main actors for the induction of microglia activation-induced Alzheimer’s Disease. Oxidative stress is one of many triggers that activate the transient receptor potential melastatin 2 (TRPM2) channel. Glutathione (GSH) is a main cytosolic antioxidant in the mammalian cells. The GSH depletion via the activation of TRPM2 induces oxidative stress and apoptosis in neuronal cells. It has not yet been researched how GSH depletion via activation of TRPM2 affects oxidative stress and apoptosis in microglial cells with the Alzheimer's disease model. The BV2 cells divided into 5 groups as control, buthionine sulphoximine (BSO and 0.5 mM for 6 h), amyloid beta (1 uM for 72 h), amyloid beta+BSO, and amyloid beta+BSO+GSH (10 mM for 2 h). In the BSO group, the levels of apoptosis, mitochondrial membrane potential, cytosolic free oxygen reactive species (cyROS), caspase (Casps) -3, Casps -8, and Casps -9 were increased as compared to the control group, although cell viability level was decreased. The expression levels of TRPM2, Casps -3, Casps -9, Bax, Bcl-2, and PARP-1 were also increased in the BSO group. In addition, their levels were further increased in the amyloid beta and BSO+amyloid beta groups as compared to the BSO group. However, the changes were modulated in the BSO+amyloid beta+GSH group by the incubation of GSH. In conclusion, the depletion of GSH increased apoptosis and cyROS levels via activation of caspases and TRPM2 in the amyloid beta-induced microglia cells. The treatment of GSH may be a potential target on the apoptosis and oxidative stress in the amyloid beta-induced microglia cells.

Ultrasensitive colorimetric detection of Hg2+ based on glutathione-modified Au nanoflowers

Due to the harm of metal mercury to the environment and the human body, there is an urgent need for exploring novel, simple, and reliable methods for the detection of Hg2+. Herein, a colorimetric method is proposed for the determination of Hg2+ based on the analyte inducing the aggregation of Glutathione-modified gold nanoflowers (GSH-Au NFs) with activated peroxidase-mimicking activity. Briefly, highly dispersed GSH-Au NFs show negligible enzyme-like activity in water. When Hg2+ is added, GSH-Au NFs would aggregate rapidly for the interaction of Hg2+ with the carboxyl and amine groups of GSH. And the aggregates exhibit high peroxidase-mimicking catalytic activity and can catalyze the color reaction of 3, 3′, 5, 5′-tetramethylbenzidine (TMB) in the presence of H2O2. Based on these phenomena, an ultrasensitive colorimetric detection method of Hg2+ has been developed. The linear range of this method is 10–300 nM and the detection limit is down to 3.9 nM, which is much lower than the standard value specified by the US EPA. The accuracy of the method has been verified in water samples, which reveals its great potential in environmental monitoring.

A Multicenter Real-World Study Evaluating the Hepatoprotective Effect of Polyene Phosphatidylcholine Against Chronic Hepatitis B.

BackgroundPolyene phosphatidylcholine (PPC) has been widely used to treat liver diseases in China. However, there is a lack of post-marketing evidence demonstrating its liver-protective efficiency among patients infected with hepatitis B virus (HBV). This study analyzed the multicenter real-world data to compare the effectiveness of PPC with those of magnesium isoglycyrrhizinate (IsoMag) and glutathione (GSH) in patients with liver injury.MethodsThis study comprised the real-world data analysis of a multicenter, retrospective observational cohort. The data were retrieved from the Cooperative Registry of the Hospital Prescription in China between 1 October 2018, and 30 September 2019. A growth curve analysis was performed to compare the effects of different treatments on liver function longitudinally for up to 30 days after treatment commencement. In addition, the dose effect of the PPC treatment was investigated.ResultsThe final cohort included 6,052 patients with approximately 8% infected with HBV (N = 471). There were 1,649, 1,750, and 2,653 patients in the PPC, GSH, and IsoMag groups, respectively, with an average age of 53.9 years. In patients with HBV infection, the PPC treatment was associated with a significant decline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (slopes: −3.7, 95% CI, −6.0 to −1.5 U/L/day; −2.4, 95% CI, −4.5 to −0.3 U/L/day, respectively). However, there were no significant differences in the effects among the three groups. In patients without HBV infection, the PPC treatment decreased ALT, AST, γ-glutamyl transferase (GGT), and albumin levels (−5.2, 95% CI, −5.8 to −4.5 U/L/day; −3.5, 95% CI, −4.2 to −2.7 U/L/day; −4.9, 95% CI, −6.2 to −3.7 U/L/day, −0.07, 95% CI, −0.09 to −0.04 g/L/day, respectively) and showed a stronger effect on lowering ALT levels than GSH (−2.6, 95% CI, −3.3 to −1.8 U/L/day, p < 0.05), as well as a stronger effect on lowering GGT levels than IsoMag (−1.4, 95% CI, −2.4 to −0.4 U/L/day, p < 0.05). PPC had no impact on prothrombin activity levels in patients with or without HBV infection. High-dose PPC exhibited a stronger effect on lowering ALT and AST levels than low-dose PPC.ConclusionThis was the first real-world multicenter study to demonstrate that PPC efficiently lowers ALT and AST levels in patients with liver diseases regardless of the status of HBV infection. PPC treatment showed a comparable or better effect compared with GSH and IsoMag treatments. High-dose PPC resulted in a stronger effect than low-dose PPC.

Improved Cytocompatibility and Reduced Calcification of Glutaraldehyde-Crosslinked Bovine Pericardium by Modification With Glutathione

Bioprosthetic heart valves (BHVs) used in clinics are fabricated via glutaraldehyde (GLUT) crosslinking, which results in cytotoxicity and causes eventual valve calcification after implantation into the human body; therefore, the average lifetime and application of BHVs are limited. To address these issues, the most commonly used method is modification with amino acids, such as glycine (GLY), which is proven to effectively reduce toxicity and calcification. In this study, we used the l-glutathione (GSH) in a new modification treatment based on GLUT-crosslinked bovine pericardium (BP) as the GLUT + GSH group, BPs crosslinked with GLUT as GLUT-BP (control group), and GLY modification based on GLUT-BP as the GLUT + GLY group. We evaluated the characteristics of BPs in different treatment groups in terms of biomechanical properties, cell compatibility, aldehyde group content detection, and the calcification content. Aldehyde group detection tests showed that the GSH can completely neutralize the residual aldehyde group of GLUT-BP. Compared with that of GLUT-BP, the endothelial cell proliferation rate of the GLUT + GSH group increased, while its hemolysis rate and the inflammatory response after implantation into the SD rat were reduced. The results show that GSH can effectively improve the cytocompatibility of the GLUT-BP tissue. In addition, the results of the uniaxial tensile test, thermal shrinkage temperature, histological and SEM evaluation, and enzyme digestion experiments proved that GSH did not affect the ECM stability and biomechanics of the GLUT-BP. The calcification level of GLUT-BP modified using GSH technology decreased by 80%, indicating that GSH can improve the anti-calcification performance of GLUT-BP. Compared with GLUT-GLY, GLUT + GSH yielded a higher cell proliferation rate and lower inflammatory response and calcification level. GSH can be used as a new type of anti-calcification agent in GLUT crosslinking biomaterials and is expected to expand the application domain for BHVs in the future.

Z-Guggulsterone Relieves Neuropathic Pain by Inhibiting the Expression of Astrocytes and Proinflammatory Cytokines in the Spinal Dorsal Horn.

ObjectiveThe study objective was to investigate whether Z-guggulsterone can relieve neuropathic pain in sciatic nerve chronic constriction injury (CCI) mice by inhibiting the expression of astrocytes and proinflammatory cytokines in the spinal dorsal horn.MethodsNeuropathic pain was induced and assessed in CCI mice. Z-guggulsterone was administered multiple times via intraperitoneal injection. Pain behaviour assessments were made by conducting paw withdrawal mechanical threshold (PWMT) and thermal withdrawal latency (TWL) tests. The expression level of the glial fibrillary acidic protein (GFAP) in the spinal dorsal horn was observed by immunofluorescence. The levels of the proinflammatory cytokines, IL-1β, IL-6 and TNF-α in the spinal cord were measured by ELISA. Data were analysed using one-way ANOVA or two-way ANOVA.ResultsThe PWMT and TWL were higher on the 5th, 7th, 10th and 14th days after CCI, the expression level of GFAP in the spinal dorsal horn was lower, and the levels of IL-1β, IL-6 and TNF-α in the spinal cord were lower in the CCI+Z-GS-L, CCI+Z-GS-M and CCI+Z-GS-H groups than in the CCI+Veh group in a dose-dependent manner (P < 0.05).ConclusionZ-guggulsterone can relieve neurological pain in CCI mice, which may be related to the inhibition of astrocytes and proinflammatory cytokines in the spinal dorsal horn.

Glutathione ameliorates Hypoxia/Reoxygenation (H/R) induced hepatocyte oxidative damage via regulating HO-1 signaling

In our study, CCK-8 assay and LDH release detection were performed to detect the optimal protective concentration of GSH on HL7702 cell viability during H/R injury. HL7702 cells were randomly divided into four groups: Control group, H/R group, H/R+GSH group, and H/R+GSH+HO-1-siRNA group. Then, reactive oxygen species (ROS) was evaluated by DHE staning, MDA, T-SOD measurements; Cell injury was detected by CCK-8, LDH release, and supernatant AST and ALT levels; Apoptosis was determined by Hoechst staining and caspase 3 level. Compared with controls, H/R caused significant HL7702 cell injury evidenced as reduced cell viability, increased LDH release and apoptotic cell death (P < 0.01), with concomitant increases in ROS and MDA production (P < 0.01), while treated with GSH in H/R group significantly attenuated oxidative injury, enhanced cell viability and downregulated cell apoptosis (P < 0.01) together with HO-1 upregulation (P < 0.01). Knockdown HO-1 by its siRNA cancelled the protective effects of GSH from H/R compared with GSH group (P < 0.01). HO-1 was induced in HL7702 exposed to H/R injury and its level was obviously overexpressed after H/R injury with GSH treatment, suggesting its protective potential in GSH against H/R injury. GSH increases the expression of HO-1, which enhanced the early antioxidative activity and played a protective role against HL7702 cells H/R injury.