Blood GSH Levels Research Articles

Glutathione level variations in brain and blood in healthy aging and Alzheimer’s disease continuum: A systematic review

AbstractBackgroundOxidative stress (OS) plays an important role in healthy and pathological aging, particularly Alzheimer’s disease (AD). To protect against the harmful effects of OS, the body uses antioxidants, the most prevalent being glutathione (reduced form, GSH) (Dwivedi et al., 2020). The consistency of GSH perturbations with age and in the AD continuum has not been systematically assessed. We address this knowledge gap by conducting a systematic review of GSH variations in brain and blood in healthy aging and the AD continuum.MethodPubMed searches were conducted up to January 2023. 15 keyword combinations were used to identify studies investigating GSH levels in (i) brain (in‐vivo using magnetic resonance spectroscopy (MRS) and in autopsy tissue using biochemical assays) and/or (ii) blood (plasma, serum) using biochemical assays (Fig1A,B). We considered individuals between 18‐39 years (yrs) as young‐adults, 40‐59 yrs as middle‐aged, and ≥60 yrs as old‐adults.Result42 studies met inclusion criteria (Fig1A,B; Fig2). BRAIN : Good to excellent reproducibility was reported by 12 MRS studies (3T, N = 6; 4T, N = 1; 7T, N = 5). For studies investigating age‐specific changes in cognitively unimpaired adults (CU, N = 6), GSH levels were significantly reduced in the majority (50%; temporal, occipital, limbic) of ROIs investigated in old‐ relative to young‐ or middle‐aged adults. Relative to CU, while brain GSH levels were reported to be lower by the majority (5/7) of AD dementia studies, MCI studies lacked consensus, with decreases (N = 3), increases (N = 2) and no significant change (N = 2) reported. BLOOD : Blood GSH levels were lower with increasing age in CU (5/7), and further decreased in patients (5/7).In both brain and blood, the majority (4/7) of AD continuum studies assessing cognition reported poorer cognitive functions with lower GSH levels.ConclusionOur systematic review demonstrates that (a) in‐vivo MRS measurements of GSH are reliable; (b) GSH levels in CU generally decrease with increasing age; and (c) GSH levels are reduced in AD relative to age‐matched CU, and reduced GSH is associated with cognitive impairment. Interventions to increase GSH levels may therefore have beneficial effects in AD.

Decrease of Cellular Communication Network Factor 1 (CCN1) Attenuates PTZ-Kindled Epilepsy in Mice.

To investigate the molecular mechanism of communication network factor 1 (CCN1) regulating pentylenetetrazol (PTZ)-induced epileptogenesis, deepen the understanding of epilepsy seizure pathogenesis, and provide new drug action targets for its clinical prevention and treatment. Differentially expressed genes (DEGs) on microarrays GSE47516 and GSE88992 were analyzed online using GEO2R. Pathway enrichment and protein-protein interaction network (PPI) analysis of DEGs were carried out using Metascape. Brain tissue samples of severe traumatic brain injury patients (named Healthy group) and refractory epilepsy patients (named Epilepsy group) were obtained and analyzed by qRT-PCR and immunohistochemistry (IHC) staining. A PTZ-induced epilepsy mouse model was established and verified. Morphological changes of neurons in mouse brain tissue were detected using hematoxylin and eosin (HE) staining. qRT-PCR was conducted to detect the mRNA expressions of apoptosis-associated proteins Bax, Caspase-3 and bcl2. TUNEL staining was performed to detect brain neuron apoptosis. The levels of myocardial enzymology, GSH, MDA and ROS in blood of mouse were detected by biochemical assay. CCN1 expression was increased in epilepsy brain tissue samples. CCN1 decreasing effectively prolongs seizure incubation period and decreases seizure duration. Silencing of CCN1 also reduces neuronal damage and apoptosis, decreases mRNA and protein expression of proapoptotic proteins Bax and Caspase-3, increases mRNA expression of antiapoptotic protein Bcl2. Moreover, decrease of CCN1 decreases myocardial enzymatic indexes CK and CK-MB levels, reduces myocardial tissue hemorrhage, and relieves oxidative stress response in hippocampal and myocardial tissue. CCN1 expression is increased in epileptic samples. CCN1 decreasing protects brain tissue by attenuating oxidative stress and inhibiting neuronal apoptosis triggered by PTZ injection, which probably by regulating Nrf2/HO-1 pathway.

Differential impacts of endogenous antioxidants on clinical symptoms and cognitive function in acute and chronic schizophrenia patients.

Impaired antioxidant defense is implicated in the pathophysiology of schizophrenia; and superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) are three first-line endogenous antioxidants. Various cognitive functions decline differently during schizophrenia course. The characteristic roles of the three antioxidants in clinical and cognitive profiles in acute and chronic phases of schizophrenia require study. We recruited 311 patients with schizophrenia, including 92 acutely exacerbated patients who had been off antipsychotics for at least 2 weeks and 219 chronic patients who had been stable on medication for at least 2 months. Blood SOD, CAT, and GSH, clinical symptoms, and nine cognitive tests were measured. Blood CAT levels were higher in the acute patients than in the chronic patients, while SOD and GSH levels were similar between them. Higher CAT levels were correlated with less positive symptoms, better working memory and problem solving in the acute phase, and less negative symptoms, less general psychopathology, better global assessment of function (GAF), and better cognitive function (in speed of processing, attention, problem solving) in the chronic period. Higher SOD levels were correlated with better GAF in the acute phase, and better speed of processing, working memory, and verbal learning and memory in the chronic period. GSH influenced neither clinical nor cognitive manifestations. This study showed that blood CAT affected different clinical and cognitive domains between acute and chronic stages of schizophrenia, SOD influenced cognitive functions in chronic state, but GSH impacted none. Further studies are needed to explore the underlying mechanisms.

Glutathione-related antioxidant defence, DNA damage, and DNA repair in patients suffering from post-COVID conditions.

Post-COVID conditions are defined as the continuation of the symptoms of Coronavirus Disease 2019 (COVID-19) 3 months after the initial Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, with no other explanation. Post-COVID conditions are seen among 30%-60% of patients with asymptomatic or mild forms of COVID-19. The underlying pathophysiological mechanisms of post-COVID conditions are not known. In SARS-CoV-2 infection, activation of the immune system leads to increased production of reactive oxygen molecules, depleted antioxidant reserve, and finally occurrence of oxidative stress. In oxidative stress conditions, DNA damage increases and DNA repair systems impair. In this study, glutathione (GSH) level, glutathione peroxidase (GPx) activity, 8-hydroxydeoxyguanosine (8-OHdG) level, basal, induced, and post-repair DNA damage were investigated in individuals suffering from post-COVID conditions. In the red blood cells, GSH levels and GPx activities were measured with a spectrophotometric assay and a commercial kit. Basal, in vitro H2O2 (hydrogen peroxide)-induced, and post-repair DNA damage (DNA damage after a repair incubation following H2O2-treatment, in vitro) were determined in lymphocytes by the comet assay. The urinary 8-OHdG levels were measured by using a commercial ELISA kit. No significant difference was found between the patient and control groups for GSH level, GPx activity, and basal and H2O2-induced DNA damage. Post-repair DNA damage was found to be higher in the patient group than those in the control group. Urinary 8-OHdG level was lower in the patient group compared to the control group. In the control group, GSH level and post-repair DNA damage were higher in the vaccinated individuals. In conclusion, oxidative stress formed due to the immune response against SARS-COV-2 may impair DNA repair mechanisms. Defective DNA repair may be an underlying pathological mechanism of post-COVID conditions.

Quantitation of Brain and Blood Glutathione and Iron in Healthy Age Groups Using Biophysical and In Vivo MR Spectroscopy: Potential Clinical Application.

The antioxidant glutathione (GSH) and pro-oxidant iron levels play a balancing role in the modulation of oxidative stress (OS). There is a significant depletion of GSH in the left hippocampus (LH) in patients with Alzheimer's disease (AD) with concomitant elevation of iron level. However, the correlation of GSH and iron distribution patterns between the brain and the peripheral system (blood) is not yet known. We measured GSH and magnetic susceptibility (e.g., iron) in the LH region along with GSH in plasma and iron in serum across four age groups consisting of healthy volunteers (age range 18-72 y, n = 70). We report non-variability of the mean GSH in the plasma and LH region across mentioned age groups. The mean iron level in the LH region does not change, but the iron level in the serum in the 51-72 y age group increases non-significantly. Regression analysis of our data indicated that GSH and iron levels (both in blood and in brain) are not related to age. This research pave the way for the identification of a risk/susceptibility biomarker for AD and Parkinson's disease from the evaluation of GSH (in plasma) and iron (in serum) levels concomitantly.

The potential role of vitamin E in patients with glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis.

As an antioxidant, vitamin E (VitE) may benefit the erythrocytes by protecting glutathione from oxidation by free radicals and peroxide-generating processes. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines when reporting this systematic review. We searched 6 electronic databases (PubMed, Scopus, Web of Science, and Cochrane Library) until May 8, 2022. We included all relevant studies. According to the study design, the Cochrane assessment tool (Risk of Bias 2), Risk Of Bias In Non-randomized Studies - of Interventions checklists, and National Institutes of Health tools were used to assess the risk of bias.Continuous data were pooled as a mean difference (MD) with a relative 95% confidence interval. The protocol was registered on PROSPERO (CRD42022333848). Six studies were included in the meta-analysis with a total of 181 patients. Compared with the control group, VitE significantly improved the hemoglobin level for chronic hemolysis (MD = 2.72 g/dL, P < .0001) and for acute hemolysis (MD = 1.18 g/dL, P < .0001). It also decreased the reticulocyte level for chronic hemolysis (MD = -1.39 P < .0001) and for acute hemolysis (MD = -1.42%, P < .0001). For before and after studies, the use of VitE significantly improved the level of packed cell volume (MD = 0.56%, P < .00001), red blood cell half-life (MD = 2.19 days, P < .0001), and decreased the reticulocytes level (MD = -1.41%, P < .00001). Among patients with glucose-6-phosphate dehydrogenase deficiency, VitE might provide benefits such as increasing the hemoglobin, packed cell volume levels, red blood cell half-life, and decreasing the reticulocyte level, so reducing hemolysis. Further high-quality, well-designed randomized controlled trials are recommended.

MiR-2115-3p inhibits ferroptosis by downregulating the expression of glutamic-oxaloacetic transaminase in preeclampsia

IntroductionRecently, ferroptosis has been reported to be closely related to preeclampsia (PE). However, the mechanisms associated with ferroptosis in PE have been poorly studied. MethodsA PE rat model was established via reduced uterine perfusion pressure (RUPP) surgery. A Ferroptosis inhibitor was used to treat the model rats. Blood pressure, urine protein, sFlt-1, GSH, GSH-PX, MDA, total Fe, Fe (II), and Fe (Ⅲ) levels were detected. Placenta morphological changes and fetal survival rate were observed and counted, respectively. miRNA sequencing and bioinformatical analysis were conducted to establish the ferroptosis-related interaction network of miRNAs-mRNAs in PE. After hypoxia treatment, cells were silenced glutamic-oxaloacetic transaminase1 (GOT1) or overexpressed miR-2115-3p/GOT1. Cellular proliferation, invasion, and reactive oxygen species (ROS) were determined. The ferroptosis-related factors levels (ACSL4, TfR1, GPX4, SCL7A11, GSH, GSH-PX, Fe (II), and MDA) were quantified. ResultsIn vivo, ferrostatin-1 attenuated ferroptosis in the PE models, significantly increasing fetal survivability. The miR-2115-3p/GOT1 pathway was screened for possible association with abnormal ferroptosis in PE. miR-2115-3p was discovered to interact with the mRNA of GOT1. Inhibition of GOT1 and overexpression of miR-2115-3p reversed the decrease in cell proliferation capacity, GSH, GSH-PX, and GPX4 levels, and the increase in ROS, ACSL4, TfR1, MDA, total Fe, and Fe (II) levels induced by hypoxia. However, simultaneous overexpression of miR-2115-3p and GOT1 reversed the above results of overexpression of miR-2115-3p. DiscussionmiR-2115-3p might interact with the GOT1 mRNA to downregulate its expression, further inhibiting the hypoxia-promoted ferroptosis in a PE model.

Evaluation of Antidiabetic Activity of Corchorus trilocularis Linn Plant Extract

Diabetes is a major health issue that has been faced by the majority of the population in the world. Extensive research is being carried out towards development of an antidiabetic component. The aim of the present research was to determine the antidiabetic activity of Corchorus trilocularis Linn plant belonging to the Tiliaceae family. The objectives were to evaluate various serum and pancreatic parameters related to evaluation of diabetes. The whole plant was extracted using various solvents. Phytochemical screening was done for the extracts. Antidiabetic activity was determined using Streptozotocin (STZ) induced diabetes model in rats using 200 mg/kg and 400 mg/kg doses of various extracts. Biochemical components like glycosylated hemoglobin (HbA1c), glutathione, creatine kinase (CK) and lactate dehydrogenase (LDH) were estimated for the collected blood samples from rats. The pancreatic tissue was homogenized and the result was subjected for estimation of TBARS (thiobarbituric acid-reactive substances), catalase, superoxide dismutase (SOD) and glutathione (GSH). Phytochemical screening showed presence of carbohydrates, glycosides, alkaloids, triterpenes, phytosterols, tannins, flavonoids, saponins, mucilage and steroids. The chloroform extract at 400 mg/kg dose significantly lowered the levels of HbA1c and restored blood GSH levels. The levels of CK and LDH were increased in diabetic rats. The treatment with chloroform extract (400 mg/kg) for 21 days significantly reduced the levels of CK when compared to diabetic rats. Extent of TBARS formed was significantly higher (p&lt;0.001) in STZ treated group. In chloroform extract (400 mg/kg) treated groups, TBARS levels have significantly decreased (p&lt;0.001). Diabetic rats treated with chloroform extract (400 mg/kg) showed significant increase (p&lt;0.01) in levels of SOD. GSH activity was reduced in pancreatic tissue of diabetic rats, compared to normal animals. These levels were significantly (p&lt;0.01, p&lt;0.001) increased with chloroform extracts (200 mg/kg and 400 mg/kg) treatment. Thus the present study showed the antidiabetic potency of Corchorus trilocularis Linn plant.Â

Identification of bacterial species in milk by MALDI-TOF and assessment of some oxidant-antioxidant parameters in blood and milk from cows with different health status of the udder.

This study aimed to identify bacterial pathogens in milk samples from dairy cows with subclinical and clinical mastitis as well as to assess the concentrations of oxidant-antioxidant parameters [malondialdehyde (MDA), reduced glutathione (GSH), and total GSH levels] in both blood and milk samples. From a total of 200 dairy cows in 8 farms, 800 quarter milk samples obtained from each udder were tested in the laboratory for the presence of udder pathogens. Cultivated bacteria causing intramammary infection from milk samples were identified by Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF). In addition, from tested animals 60 cows were selected includıng 20 healthy cows that were CMT negative, 20 cows with subclinical mastitis (SM), and 20 cows with clinical mastitis (CM) for detection of MDA, GSH, and total GSH levels in blood and milk samples. Three hundred and eighty (47.5%; 380/800), 300 (37.5%; 300/800), and 120 (15%; 120/800) of milk samples, respectively were CMT positive or SM and CM, and those positives were cows from different farms. We observed that 87.4% (332/380), 25.3% (76/300), and 34.2% (41/120) of cows with CMT positive, CMT negative, and CM had bacterial growth. The most predominantly identified bacteria were Staphylococcus chromogenes (18.7%) obtained mainly from SM and Staphylococcus aureus (16.7%) as the most frequent cause of CM. According to our results, dairy cows with CM had the highest MDA levels, the lowest GSH, and total GSH levels in both blood and milk samples however, high MDA levels and low GSH levels in milk samples with SM were observed. Based on our results, lipid oxidant MDA and antioxidant GSH could be excellent biomarkers of cow's milk for developing inflammation of the mammary gland. In addition, there was no link between nutrition and MDA and GSH levels.

Ethanol extract of the mushroom Coprinus comatus exhibits antidiabetic and antioxidant activities in streptozotocin-induced diabetic rats

Context Edible mushrooms have a long history of use in traditional Chinese or Japanese medicine. Coprinus comatus (O.F. Müll.) Pers. (Agaricaceae) contains antioxidant and antidiabetic agents. Objective To identify the benefits of ethanol extracts of the C. comatus fruit body in streptozotocin-induced hyperglycaemic rats by evaluating their blood glucose, glycosylated haemoglobin (HbA1c), insulin, glucagon-like peptide-1 (GLP-1), dipeptidyl peptidase-4 (DPP-4), and glutathione (GSH) levels, with and without extract administration. Materials and methods Wistar rats were either left untreated or were administered 45 mg/kg body weight (BW) streptozotocin; 45 mg/kg BW metformin; or 250, 500, or 750 mg/kg BW extract for 14 days. The blood glucose, GLP-1, DPP-4, GSH, insulin, and HbA1c levels were determined. Data were analysed using analysis of variance and Duncan’s multiple range tests. Results Preliminary data showed that administration of C. comatus ethanol extract dose of 250, 500, and 750 mg orally has no toxicity effects after 24 h administration. The ethanolic extract of fruiting body of C. comatus considerably reduced the rat’s fasting blood glucose levels 26.69%, and DPP-4 6.97% at dose of 750 mg. The extract reduced HbA1c 4–4.30%, increased GLP-1 71.09%, GSH 11.19% at dose of 500 mg, and increased insulin levels 13.83%. Extracts contain bioactive compounds such as flavonoid, alkaloid, terpenoids, vitamins C and E, rutin, and saponin. Conclusions The C. comatus extract can be used as herbal medicine that reduces diabetic symptoms. Further investigation on C. comatus extracts should be conducted with gas chromatography-mass spectrometry to characterise the bioactive compounds.

Personalized profiles of antioxidant signaling pathway in patients with tuberculosis

The non-protein thiol glutathione is protective against infection by Mycobacterium tuberculosis (MTB) and, together with the transcription factor NRF2 (the nuclear factor erythroid 2-related factor 2), plays a crucial role in counteracting MTB-induced redox imbalance. Many genes implicated in the antioxidant response belong to the NRF2-signalling pathway, whose central role in the pathogenesis of tuberculosis (TB) has been recently proposed. In this study, we measured GSH levels in blood of patients with active TB and analysed the individual NRF2-mediated redox profile, in order to provide additional tools for discriminating the pathologic TB state and addressing therapeutic interventions. Our findings show a systemic individual modulation of GSH and NRF2 signaling pathway in patients with TB, with a "personalized" induction of NRF2-target genes. This study can provide useful tools to monitor the course of the infection and address patients' treatment.

Altered central and blood glutathione in Alzheimer\u2019s disease and mild cognitive impairment: a meta-analysis

BackgroundIncreasing evidence implicates oxidative stress (OS) in Alzheimer disease (AD) and mild cognitive impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS-mediated neurodegeneration, though studies of post-mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of the brain and blood GSH may shed light on GSH changes earlier in the disease.AimTo quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta-analyses.MethodStudies with in vivo brain or blood GSH levels in MCI or AD with a HC group were identified using MEDLINE, PsychInfo, and Embase (1947–June 2020). Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) versus non-MEGA-PRESS) and blood GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger’s test were used to assess heterogeneity and risk of publication bias, respectively.ResultsFor brain GSH, 4 AD (AD=135, HC=223) and 4 MCI (MCI=213, HC=211) studies were included. For blood GSH, 26 AD (AD=1203, HC=1135) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH overall did not differ in AD or MCI compared to HC; however, the subgroup of studies using MEGA-PRESS reported lower brain GSH in AD (SMD [95%CI] −1.45 [−1.83, −1.06], p<0.001) and MCI (−1.15 [−1.71, −0.59], z=4.0, p<0.001). AD had lower intracellular and extracellular blood GSH overall (−0.87 [−1. 30, −0.44], z=3.96, p<0.001). In a subgroup analysis, intracellular GSH was lower in MCI (−0.66 [−1.11, −0.21], p=0.025). Heterogeneity was observed throughout (I2 >85%) and not fully accounted by subgroup analysis. Egger’s test indicated risk of publication bias.ConclusionBlood intracellular GSH decrease is seen in MCI, while both intra- and extracellular decreases were seen in AD. Brain GSH is decreased in AD and MCI in subgroup analysis. Potential bias and heterogeneity suggest the need for measurement standardization and additional studies to explore sources of heterogeneity.

Effect of glucose on reduced glutathione level in Malay uncomplicated type 2 diabetes patients

Background: Increasing blood sugar level may increase free radical compounds in type 2 diabetes. Free radical compounds can cause oxidative stress, thereby decreasing endogenous antioxidants such as reduced glutathione (GSH).&#x0D; Objective: This study aimed to determine whether random blood glucose levels affect GSH in type 2 diabetes patients within the Malay race.&#x0D; Methods: This study was observational with case-control, involving 25 patients with uncomplicated type 2 diabetes (receiving metformin and/or glimipiride) and 25 healthy controls. Random blood glucose levels were determined using ACCU-CHECK® Kit. Blood GSH levels were determined by Sigma GSH Assay Kit.&#x0D; Results: Results show that type 2 diabetes patients have a significantly lower random blood glucose level compared with those of age-matched normal subjects (p&lt;0.0001). Type 2 diabetic patients had significantly lower levels of GSH (p=0.00) than those of age-matched normal subjects. We found a moderate negative correlation (r=-0.437 and p=0.02) between the level of random blood glucose and the level of GSH.&#x0D; Conclusion: The depletion of GSH during hyperglycemia may neutralize the free radicals indirectly generated by the abundant of glucose.&#x0D;

​Evaluation of Various Biochemical Parameters in the Serum and Tissues of Lambs with White Muscle Disease

Background: In this study, the effects of White Muscle Disease (WMD) on certain blood parameters, MDA and GSH levels in liver and thyroid tissues and the thyroid hormones were investigated in sheep. Methods: Sixteen lambs (8 with WMD, 8 controls) of similar age, 3 to 50 days old, selected from the same region were used in the study. Blood samples were taken from all animals. One ml Vitamin E + Se were injected (I/M) to the lambs with WMD and blood and tissue samples were collected after the treatment as well. The serum Ca, P, T3, T4, albumin, globulin, total protein, glutathione (GSH) values were analyzed by an auto-analyzer. Malondialdehyde (MDA) and GSH amounts of the liver and thyroid tissues were also determined. Result: The low Ca ion amount in lambs with WMD was found to have increased after injections of vitamin E + Se. P levels followed the same pattern. Total protein, albumin and globulin levels increased after treatment. It was determined that there was a decrease in T3 levels and an increase in T4 levels in patient lamb sera. The levels of GSH in both the liver and thyroid tissues were found to have decreased and statistical significance (at what level) was only found for the liver GSH levels. MDA levels in the hepatic and thyroid tissues were found to have slightly increased in the WMD group. In conclusion, serum differences in Ca, P, albumin, globulin, total protein, T3, T4, GSH, GSH and MDA levels were statistically significant between the groups.

Estrogen Replacement Therapy Induces Antioxidant and Longevity-Related Genes in Women after Medically Induced Menopause.

Females live longer than males in many species, including humans, and estrogens are in part responsible for this protection against aging. We reported previously that estrogens can protect rats against oxidative stress, by inducing antioxidant and longevity-related genes. Thus, this study was aimed at confirming the ability of estrogens to upregulate antioxidant and longevity-related genes in humans. For this purpose, we selected 16 women of reproductive age (18-42 years old) undergoing a fertility treatment that includes a medically induced menopause, at the Valencian Infertility Institute. We took blood samples at each time point of the treatment (basal, induced menopause, estrogen, and estrogen plus progesterone replacement therapy). mRNA expression of antioxidant and longevity-related genes in peripheral blood mononuclear cells (PBMC) was determined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Determination of reduced glutathione (GSH) in total blood was carried out using high-performance liquid chromatography (HPLC). As expected, we found that medically induced menopause significantly decreased sexual hormone (estrogens and progesterone) levels. It also lowered glutathione peroxidase (GPx), 16S rRNA, P21, and TERF2 mRNA expression and blood GSH levels. Estrogen replacement therapy significantly restored estrogen levels and induced mRNA expression of manganese superoxide dismutase (MnSOD), GPx, 16S rRNA, P53, P21, and TERF2 and restored blood GSH levels. Progesterone replacement therapy induced a significant increase in MnSOD, P53, sestrin 2 (SENS2), and TERF2 mRNA expression when compared to basal conditions. These findings provide evidence for estrogen beneficial effects in upregulating antioxidant and longevity-related genes in women.

Effects of sulforaphane on cognitive function in patients with frontal brain damage: study protocol for a randomised controlled trial

IntroductionMany patients with frontal brain damage show serious cognitive function deficits, which hamper their quality of life and result in poor clinical outcomes. Preclinical research has shown that sulforaphane can...

The Role of Hydrogen Sulfide in Chronic Unpredictable Stress-Induced Gastric Lesions.

The aim of this study was to investigate the possible protective role of Hydrogen sulfide on chronic unpredictable stress (CUS) -induced gastric lesions. Materials and methods: 40 rats were divided into 4 groups: control group, stressed rats group, stressed + Aminooxyacetic acid (AOAA) (inhibitor of H2S synthesis; 50mg/kg/48hour; IP), stressed + Sodium hydrosulfide (NaHS) (donor of H2S, 5mg/kg/48hour; IP). In all the groups exposed to CUS, a set of chronic unpredictable stressors was applied for 6 weeks in random order. At the end of experimental protocol blood samples, gastric content and gastric tissues samples were collected. Gastric tissues histopathological changes were evaluated by macroscopic and microscopic examination. Gastric content pH, serum MDA level, whole blood GSH level were estimated. Expression of Caspase-3 (apoptotic marker) and BCL-xl (anti-apoptotic marker) was assessed by immunohistochemistry. Results: In all the groups exposed to CUS, there was a significant reduction in gastric pH value and a range of gastric lesions ranging from superficial to deep ulceration as evident by macroscopic and microscopic examination. Also, there was significant elevation in MDA serum level and significant reduction in anti-oxidant GSH blood level. In all stressed rats, the expression of Caspase-3 was significantly higher whereas a significant decrease in expression of anti-apoptotic protein BCL-xl was observed. These findings were aggravated by AOAA while using NaHS improved them. Conclusion: it seems that increasing bioavailability of H2S could have a protective role against CUS induced gastric lesions. The results suggest that this protection could be through anti-oxidant and anti-apoptotic effects.

Evaluating Hyperthyroidism-Induced Liver Injury Based on In Situ Fluorescence Imaging of Glutathione and Phosphate via Nano-MOFs Sensor

Hyperthyroidism-induced liver injury is quite common in clinical settings. Therefore, developing rapid and simple methods for the assessment of hyperthyroid liver injury is of great significance. Considering phosphorus metabolism is disordered because of hyperthyroidism, and the hyperthyroid liver injury is closely related to the abnormal level of glutathione (GSH). Thus, development of a new method that can simultaneously detect changes in blood phosphorus and GSH levels of serum, liver, kidney, and other organs to assess the degree of hyperthyroid liver injury is necessary for clinical medical research. Herein, a novel fluorescent metal-organic frameworks (MOFs) nanoprobe using the UiO-66(OH)2 as core and Cu-MOFs as shell was designed and synthesized. Through the specific action between Zr (IV) and phosphate, and the combine interaction of MOFs active center Cu (II) and GSH, high sensitivity and specific fluorescence detection of phosphate and GSH were achieved, respectively. Finally, the nanosensor was applied for evaluating different degrees of hyperthyroid liver injury in mice models and realized the monitoring of serum, liver, kidney, and other organs' blood phosphorus and GSH levels, and found that the levels of phosphate and GSH in serum were negatively correlated with the degree of hyperthyroid liver injury, while the changes of phosphate and GSH levels in the liver and kidney organs were positively correlated with the degree of hyperthyroid liver injury. In general, the present works provide a new way to effectively evaluate liver injury induced by hyperthyroidism in the early clinical stage.

The role of apoptosis and autophagy in the insulin-enhancing activity of oxovanadium(IV) bipyridine complex in streptozotocin-induced diabetic mice.

Metal-based therapies (e.g. Vanadium) possess an attractive proposition in medicinal treatment of diabetes mellitus. Defective insulin secretion can result from impaired β-cell function which is mediated by many process including apoptosis and autophagy. In this study. diabetes was induced by administration of streptozotocin then treatment was performed by vanadyl sulfate and [VO(bpy)2 Cl] Cl.H2O complex. Blood glucose level, AST, ALT, BUN, CR, TCHO, TG and total protein were determined in serum. MDA, NO, erythrocyte GSH and SOD were estimated. LC3 and Caspase 3 levels in pancreatic cells were assessed by flow cytometer. Histopathological investigation of pancreatic tissue was performed. Results of Diabetic group showed a significant increase in transaminases activities, TCHO, TG, MDA, NO and Caspase 3 levels and significant decrease in TP, GSH, SOD and LC3 levels. Oral administration of vanadium complex resulted in normoglycemia, significant increase in blood GSH, SOD, TP and LC3 levels, significant decrease in ALT, AST, BUN, TCHO, TG, MDA and NO and Caspase 3 levels. In addition, proliferative effect of complex prevents islet atrophy. From previous results, the insulin-enhancing effect induced by this complex indicated that this new complex can be a valuable candidate as insulin-enhancing and antioxidant compound than inorganic vanadyl sulfate.

Effects of Wuweizi syrup on brain aging mice model induced by d-galactose

ObjectiveTo observe the effect of Wuweizi syrup on brain aging mice model induced by d-galactose in mice. Methods72 mice were randomly divided into blank group, model group, naokangling group and low, middle and high dose Wuweizi syrup group. After 3 days of adaptive feeding, except for the blank group, the rest mice were subcutaneously (sc) injected with d-galactose 1.25 g/kg at neck back to replicate the aging model. Sc injection was given for 40 consecutive days, and corresponding drugs were given by gavage on the 11th day of modeling. On the 39th day, the dark experiment was carried out to measure the learning ability of mice. After the last administration for 2 h, brain, liver, thymus and spleen were taken and weighed to calculate the organ index. Blood was taken and CAT, GSH and SOD levels in whole blood were determined. Some brain and liver tissues were taken to prepare homogenates, and MDA levels in tissue homogenates and plasma were measured. Brain, liver, thymus and spleen were stained with HE, and pathological sections were made for observation under light microscope. ResultsCompared with the blank group, in the model group, the incubation period of mice was significantly reduced and the number of shuttle back and forth was significantly increased (P < 0.01); Spleen and brain indexes decreased significantly (P < 0.05), thymus indexes were decreased significantly, and liver indexes were increased significantly (P < 0.01); The levels of CAT, GSH and SOD in whole blood were significantly decreased (P < 0.01); MDA levels in liver homogenates, brain homogenates and plasma were significantly increased (P < 0.01); Pathological changes of brain, liver, thymus and spleen were observed under microscope. Compared with the model group, naokangling group and low, middle and high dose Wuweizi syrup group can significantly improve the incubation period of mice and reduce the number of shuttle back and forth (P < 0.01), can decrease or increase the organ index with different degree (P < 0.01 or P < 0.05), can significantly increase the levels of CAT, GSH and SOD in whole blood (P < 0.01), and significantly reduce the levels of MDA in plasma, liver homogenate and brain homogenate (P < 0.01), as well as can improve pathological changes of brain, liver, thymus and spleen with different degree. ConclusionThe mice aging model was successfully replicated, and Wuweizi syrup can significantly improve the memory, biochemical indexes and pathological status of brain aging model mice.