Lower GSH Research Articles

Blockade of Renin Angiotensin System Ameliorates the Cardiac Arrhythmias and Sympathetic Neural Remodeling in Hearts of Type 2 DM Rat Model.

The present study was designed to investigate the effects of renin angiotensin system (RAS) blockade on cardiac arrhythmias and sympathetic nerve remodelling in heart tissues of type 2 diabetic rats. Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group: normal rats, b) DM group; after type 2 diabetes induction, rats received 2ml oral saline daily for 4 weeks, c) DM+ ACEi: after type 2 diabetes induction, rats were treated with enalapril (10 mg/kg, orally for 4 weeks) and d) DM+ ARBs: after type 2 diabetes induction, rats were treated with losartan (30 mg/kg, orally for 4 weeks). In type 2 diabetic rats, the results demonstrated significant prolongation in Q-T interval and elevation of blood sugar, HOMA-IR index, TC, TGs, LDL, serum CK-MB, myocardial damage, myocardial MDA, myocardial norepinephrine and tyrosine hydroxylase (TH) density with significant reduction in serum HDL, serum insulin and myocardial GSH and CAT. On the other hand, blockade of RAS at the level of either ACE by enalapril or angiotensin (Ag) receptors by losartan resulted in significant improvement in ECG parameters (Q-T), cardiac enzymes (CK-MB), cardiac morphology, myocardial oxidative stress (low MDA, high CAT and GSH) and myocardial TH density. RAS plays a role in the cardiac sympathetic nerve sprouting and cardiac arrhythmias induced by type 2 DM and its blockade might have a cardioprotective effect via attenuation of sympathetic nerve fibres remodelling, myocardial norepinephrine contents and oxidative stress.

Multi-stimuli responsive mesoporous silica-coated carbon nanoparticles for chemo-photothermal therapy of tumor

In this work, a traceable dual-porous mesoporous silica-coated mesoporous carbon nanocomposite (MCN@Si) with high drug loading capacity and high photothermal conversion efficiency (30.5 %) was successfully prepared. Based on the nanocomposite, a pH/redox/near infrared (NIR) multi-stimuli responsive drug delivery system was constructed to realize the accurate drug delivery, drug controlled release and chemo-photothermal synergistic antitumor therapy. MCN@Si was used as a vehicle to load doxorubicin (DOX) with a high drug loading efficacy of 48.2 % and a NIR absorbance agent for photothermal therapy and NIR thermal imaging. Carbon dots (CDs) with proper size were covalently attached to the surface of MCN@Si via disulfide bonds to block the mesopores, preventing DOX premature release from DOX/MCN@Si-CDs. Besides, CDs were served as fluorescent probe to prove the visualization potential of the drug delivery system. DOX was rapidly released at the condition of low pH and high GSH concentration due to the breakage of disulfide bonds and protonation of DOX. Moreover, the local hyperthermia generated by MCN@Si-CDs under NIR irradiation could not only directly kill cells, but also accelerate DOX release and enhance cells sensitivity and permeability. Two-dimensional cells and three-dimensional tumor spheroids assays illustrated that DOX/MCN@Si-CDs + NIR group exhibited a superior thermochemotherapy synergistic treatment effect and the combination index (CI) was 0.378. Biodistribution study showed the biosecurity of preparations and its prolonged detention time in tumor sites. Besides, antitumor experiment in vivo also performed the excellent synergistic inhibition effect. All the results demonstrated that DOX/MCN@Si-CDs is a traceable multi-stimuli responsive nanodelivery system and can achieve efficient chemo-photothermal synergistic antitumor therapy.

Serum Caspase-1 levels in women with polycystic ovary syndrome

ObjectiveCaspase-1 is implicated in several important inflammatory diseases and controls adipocyte differentiation and insulin sensitivity. Interleukin-10 (IL-10) is an anti-inflammatory cytokine and plays an important role in chronic inflammatory conditions. This study was planned to determine if there is any relationship between Caspase-1 and IL-10 levels in women with PCOS. Materials and methodsForty-two women with PCOS and thirty-seven healthy controls were evaluated in this controlled clinical study. Caspase-1 and IL-10 levels, serum lipid sub-fractions, fasting glucose, fasting insulin and other hormones (gonadotropins, androgens), malondialdehyde (MDA) and glutathione (GSH) levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. ResultsFree androgen index (FAI), HOMA-IR, MDA and Caspase-1 levels were significantly higher in subjects with PCOS. However, the women with PCOS had considerably lower GSH concentration levels than healthy subjects. Serum IL-10 levels were higher in study subjects than in controls, though it was statistically insignificant. Caspase-1 was positively associated with IL-10. ConclusionThese outcomes propose that Caspase-1 may have a role in triggering the processes leading to chronic low-grade inflammation in women with PCOS, independent of insulin resistance, androgen excess and oxidative stress. Nevertheless, the precise role of Caspase-1 in the pathogenesis of the disease remains to be elucidated.

L-Glutamine Supplementation Improves the Benefits of Combined-Exercise Training on Oral Redox Balance and Inflammatory Status in Elderly Individuals.

Although regular combined aerobic-resistance exercises can ameliorate the inflammatory status and redox balance in elderly population, it is unclear whether protein or specific amino acid supplementation could improve such benefits. Therefore, we aimed to evaluate the inflammatory status and redox indexes through of the saliva of 34 elderly subject nonpractitioners (NP group, 73.3 ± 6.6 years) and 49 elderly subject practitioners of a combined-exercise training in moderate intensity (CET group, 71.9 ± 5.8 years) before (pre) and after (post) 30 days of supplementation with L-glutamine (Gln) or placebo (PL). Our results showed that, both in pre- and postsupplementation, the salivary levels of nitric oxide (NO·) and TNF-α were lower, whereas the levels of uric acid and IL-10 (as well as IL-10/TNF-α ratio) were higher in the CET groups than in the NP groups. In postsupplementation, both groups supplemented with Gln (NP-Gln and CET-Gln) showed higher salivary uric acid levels compared to baseline. In addition, lower NO· levels were found in the CET-Gln group postsupplementation than presupplementation values. Whereas the CET-Gln group showed lower GSH levels postsupplementation, NP-Gln subjects showed lower GSSG levels at the same time point, both compared to baseline. Interestingly, salivary peroxidase activity was lower only in NP groups (NP-PL and NP-Gln) postsupplementation than baseline values. A positive significant correlation between salivary peroxidase activity and GSH levels, and also between salivary peroxidase activity and uric acid levels were observed in the CET-Gln group both pre- and postsupplementation. No differences were found in albumin, total antioxidant activity (TEAC), and reducing power analysis between groups, pre- or postsupplementation. In conclusion, the elderly subjects from the CET group showed a better inflammatory response and redox balance and, for the first time, it was shown that daily supplementation with Gln for 30 days can improve these benefits with putative association with a healthy aging.

Renin angiotensin system blockage by losartan neutralize hypercholesterolemia-induced inflammatory and oxidative injuries

ABSTRACT Objectives: This study explores the protective role of losartan (LT) against oxidative and inflammatory damages in different physiological systems including heart, liver, and kidney tissue in hypercholesterolemic rats. Methods: After induction of hypercholesterolemia by high cholesterol diet for 6 weeks, LT was administered for 4 weeks. In serum, the levels of lipoproteins, aminotransferases, creatine kinases, urea, apoptosis, and inflammatory markers were measured. In cardiac, hepatic, and renal tissues, lipid peroxidation product and GSH as well as antioxidant enzymatic activities were assayed. Finally, histopathological assessment evaluated the structural damage in cardiac, hepatic, and renal tissues. Results: Serum markers of cardiac, hepatic, and renal toxicities including creatine kinases, aminotransferases, and urea were attenuated by LT in hypercholesterolemic animals. Moreover, LT markedly corrected the elevated levels of lipoproteins, apoptosis, and inflammatory biomarkers. Hypercholesterolemia-induced lipid peroxidation, low GSH levels, and diminished activities of antioxidant enzymes were prominently improved in LT treated animals. Histopathological alterations by hypercholesterolemia in heart, liver, and kidney tissues were ameliorated by LT. Conclusion: This study confirmed the pathological enrollment of renin–angiotensin system in hypercholesterolemia-associated metabolic alterations. LT had a significant cardiac, hepatic, and renal protective role against these impairments through down-regulation of oxidative damage, inflammation and necrosis.

Vulnerability of glutathione-depleted Crassostrea gigas oysters to Vibrio species

Glutathione (GSH) is a major cellular antioxidant molecule participating in several biological processes, including immune function. In this study, we investigated the importance of GSH to oysters Crassostrea gigas immune response. Oysters were treated with the GSH-synthesis inhibitor buthionine sulfoximine (BSO), and the function of immune cells and mortality were evaluated after a bacterial challenge with different Vibrio species. BSO caused a moderate decrease (20–40%) in GSH levels in the gills, digestive gland, and hemocytes. As expected, lower GSH decreased survival to peroxide exposure. Hemocyte function was preserved after BSO treatment, however, oysters became more susceptible to challenges with Vibrio anguillarum, V. alginolyticus, or V. harveyi, but not with V. parahaemolyticus and V. vulnificus, indicating a species-specific vulnerability. Our study indicates that in natural habitats or in mariculture farms, disturbances in GSH metabolism may pre-dispose oysters to bacterial infection, decreasing survival.

Effect of Cisplatin on Cerebellar Cortex of Albino Rat and Possible Protective Role of Granulocyte Colony Stimulating Factor versus Citrullus Lanatus Juice: A Histological Study

Background: Cisplatin has a major antitumor effect against a broad range of solid tumors. Yet, its clinical use is limited by its harmful effects especially on the nervous system.Aim of the work: Assessment of the effect of cisplatin on histological structure of cerebellar cortex and the possible protective role of granulocyte colony stimulating factor (G-CSF) versus citrullus lanatus juice. Materials and methods: Forty adult male albino rats were assigned to a group of four: Control group, group I: received cisplatin (10 mg/kg) on the 6th and 13th days of the study via intraperitoneal (IP) injection, group II: received G-CSF (50 µg/kg) for five consecutive days via subcutaneous injection then received as group I, group III: received cisplatin as group I as well as citrullus lanatus juice (4 ml/kg) daily for 16 days via oral gavage. Blood samples were taken to measure plasma malondialdehyde (MDA) and reduced glutathione (GSH) levels. Cerebellar biopsies were processed for light microscopy using H&E and immunohistochemical stains (glial fibrillary acidic protein (GFAP) & caspase-3) as well as for electron microscopy. Morphometric and statistical studies were done for number of Purkinje cells, thickness of granular layer, area percent of GFAP positive cells and optical density of caspase-3 positive cells.Results: Group I showed significantly high MDA and significantly low GSH levels, shrinkage, distortion, deep staining of disarranged Purkinje cells with nuclear pyknosis, swollen mitochondria with destroyed cristae and dilated Golgi apparatus. Separated granule cells were shrunken with dark irregular nuclei. Results were confirmed by morphometric and statistical studies. These changes were ameliorated in both group II and III with great extent in group II than in group III. Conclusion: G-CSF could improve cisplatin induced cerebellar cortical changes better than citrullus lanatus juice.

The influence of tobacco smoke exposure on selected markers of oxidative stress, kidneys and liver function in the serum of rats with streptozotocin-induced diabetes.

The significance of the free radicals is emphasized in the pathophysiology of diabetes and the progression of chronic diabetic complications. Smoking cigarettes increases the risk of developing type II diabetes and intensifies pathophysiological processes during the development of type I diabetes. Tobacco smoke is also additional source of free radicals. Moreover, smoking causes variety of adverse effects on organs, that have no direct contact with the tobacco smoke itself. The objective of the study was to examine the effects of tobacco smoke on the serum concentrations of relevant oxidative stress markers such as total protein (TP), reduced glutathione (GSH), glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS), as well as renal (creatinine, urea) and liver function (alkaline phosphatase, ALP; alanine aminotransferase, ALT; aspartate aminotransferase, AST) among animals with induced diabetes after administration of a single dose of streptozotocin (65 mg/kg, ip). The markers of oxidative stress and biochemical parameters were determined using spectrophotometric methods. As a biomarker of exposure to tobacco smoke, cotinine was determined using high-performance liquid chromatography with diode array detection (HPLC-DAD). Tobacco smoke exposure of diabetic rats was manifested by significantly elevated liver enzymes activity - ALT (p < 0.05) and ALP (p < 0.01), higher creatinine and urea concentration (p < 0.01), lower GSH amount (p < 0.05), and higher GST activity (p < 0.05). Tobacco smoking induce liver and renal damage through the mechanisms including increased oxidative stress.

The Healing Effects of Hydroalcoholic Extract of Carum copticum L. on Experimental Colitis in Rats.

Background:Ulcerative colitis is an inflammatory disease with indefinite treatment. The present study aimed to assess the anti-inflammatory and antioxidant effects of Carum copticum L. (CC) extract on induced colitis in rats. Methods: Sixty male rats were randomly divided into six groups (n=10 per group). Acetic acid-induced colitis rats were orally administered with doses of 100, 200, and 400 mg/kg CC extract, and 100 mg/kg sulfasalazine for seven consecutive days, respectively. Colonic biopsies were taken to measure histopathological parameters as well as the tumor necrosis factor (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO), malondialdehyde (MDA), and glutathione (GSH). Data analysis was performed using the one-way ANOVA and Tukey’s test for normally distributed data. Kruskal-Wallis test followed by Dunn’s test was used for non-normally distributed data. The analysis was performed at P≤0.05 using SigmaStat software (version 10.0). Results:The control colitis group had a significantly higher total colitis index (P=0.01), TNF-α (P=0.01), IL-6 (P=0.01), MPO (P=0.01), and MDA (P=0.01); and lower GSH (P=0.01) than those of the sham group. The colitis group receiving a dose of 200 mg/kg/day CC extract had a significantly lower total colitis index (P=0.01), TNF-α (P=0.01), IL-6 (P=0.01), MPO (P=0.01), and MDA (P=0.01); and higher GSH (P=0.01) than those of the control colitis group. The colitis group receiving a dose of 200 mg/kg/day CC extract had a significantly lower total colitis index (P=0.04), TNF-α (P=0.03), IL-6 (P=0.04), MPO (P=0.03), and MDA (P=0.03); and higher GSH (P=0.01) than those of the colitis group receiving sulfasalazine. Conclusion: The present study revealed that CC extract had healing effects on colitis, possibly due to its antioxidant and anti-inflammatory properties.

Evaluating the Protective Effects of Mitochondrial Glutathione on Cerebral Ischemia/Reperfusion Injury via Near-Infrared Fluorescence Imaging

Cerebral ischemia/reperfusion (I/R) is common and intractable in the clinic, associated with the outburst of reactive oxygen species (ROS) in mitochondria. Although numerous research studies have been conducted to prove the protective-effect roles of glutathione (GSH) in this event, the changes in GSH concentrations in living cells remain largely unexplained, and there is scarce evidence by fluorescence imaging for its roles. Herein we have designed and synthesized two distinctive "off-on" near-infrared (NIR) fluorescent probes BCy-SeSe and BCy-SS based on a new fluorophore BCy-Keto for specific response to mitochondrial GSH changes during the cerebral I/R process. Both of them exhibit powerful targeting capability in mitochondria and excellent photophysical properties toward endogenous GSH with high selectivity and sensitivity. In contrast to BCy-SS, BCy-SeSe was screened for biological application on account of its faster response rate. We have utilized BCy-SeSe to real-time image GSH during the cerebral I/R process in living cells and the mice focal cerebral ischemia model (middle cerebral artery occlusion, MCAO), and these intensive studies revealed that low GSH levels were associated with aggravation of apoptosis and cerebral infarction. Pretreatment with GSH synthase inhibitor aggravates damage while GSH-ester alleviates damage, confirming that GSH is effective on the cerebrum for protection from I/R. All the results demonstrated that the probes were powerful tools for investigating mitochondrial GSH during the I/R process in living cells and in vivo.

Association of advanced glycation end products (AGEs) with endothelial dysfunction, oxidative stress in gestational diabetes mellitus (GDM)

Advanced glycation end products (AGEs) are major risk factors for vascular complications in diabetes. Its role in gestational diabetes mellitus (GDM) and vascular complications in GDM is not known. The present study was aimed to study the association of AGEs with GDM and vascular inflammation. Plasma samples from normal pregnant and GDM women (n = 50 each) were obtained from two tertiary referral centers in Tamil Nadu, India. Quantification of AGEs, methylglyoxal (MGO), ICAM-1, and malondialdehyde (MDA) were performed by commercially available ELISA kits. The third trimester fasting blood sugar (101.35 ± 26.15 vs. 81.63 ± 6.14, p < 0.002) and postprandial blood sugar (150.69 ± 23.07 vs 105.79 ± 11.99, p < 0.0001) were significantly high in GDM women compared to normal pregnant women. The concentrations of AGEs (13.18 ± 8.74, p < 0.001), MGO (15.7 ± 13.54, p < 0.02), and ICAM-1 (217.8 ± 86.92, p = 0.005) were significantly higher in GDM women compared to AGEs (2.68 ± 0.89), MGO (9.26 ± 5.38), and ICAM-1 (142.3 ± 38.21) in normal pregnant women. Further, elevated levels of MDA concentration (0.64 ± 0.08, p < 0.002) and low GSH levels (0.19 ± 0.1, p < 0.0001) in the GDM women were indicative of oxidative stress. AGE levels significantly correlated with MDA concentration which indicates AGEs may be responsible for oxidative stress in GDM women. Further, elevated level of ICAM-1 in GDM women suggests endothelial activation which may impact endothelial function. Thus, AGEs may be used as a biomarker during pregnancy to predict vascular complications due to GDM.

The evaluation of oxidative stress parameters in the benign prostatic hyperplasia, prostatitis and prostate cancer

Aim: Recently, oxidative stress has been well known that it has especially important a role in benign prostatic hyperplasia, prostatitis, and prostate cancer. The present study has planned to estimate parameters of the oxidative stress and the antioxidant status in patients with benign prostatic hyperplasia, prostatitis and prostate cancer.Material and Method: For this aim totally fourty men with benign prostatic hyperplasia (n=14), prostatitis (n=15) and prostate cancer (n=11) without any other chronic disease, and who not use cigarettes and alcohol were subjected. Venous blood samples were taken. Thiobarbituric acid reaction (TBARS), total oxidant status (TOS), total antioxidant capacity (TAC), glutathione (GSH) levels, and catalase (CAT) activity in serum were assessed in patient with prostatitis, and prostate cancer compared to benign prostatic hyperplasia.Results: It was viewed that GSH levels were significantly lower, TBARS and TOS levels were significantly higher in patients with of prostate cancer compared to benign prostatic hyperplasia. Also, GSH and CAT significant different was determined in prostatitis compared to BPH. Oxidative stress may be concluded in prostate cancer and prostatitis, proved via the higher TBARS levels and lower GSH levels.Conclusion: The increased activity of antioxidant enzyme may be a compensatory regulation in response to oxidative stress.

Circulating antioxidant levels in systemic lupus erythematosus patients: a systematic review and meta-analysis.

Aim: To derive a precise estimation on plasma/serum level of SOD, GPx, CAT and GSH levels in systemic lupus erythematosus (SLE) patients. Methods: A total of 36 articles from electronic databases were finally included with 1120 SLE patients and 1024 healthy controls considered for antioxidant levels. Results: The levels of CAT and GSH were significantly lower, while SOD and GPx levels were slightly lower in patients with SLE compared with healthy controls. Subgroup analysis indicated that Arabs, ages ≥40 and SLE diseases activity index <6 had a significant association of SOD and CAT levels with SLE patients. Conclusion: The results demonstrated a significant lower CAT and GSH levels and also revealed no significant difference for SOD and GPx levels in SLE patients.

TLR4 promotes liver inflammation by activating the JNK pathway.

Drug-induced liver injury has become a serious public health problem that cannot be ignored. Although the mechanism of acetaminophen (APAP)-induced liver injury has been investigated for several decades, there are still many deficiencies. However, only a deeper study of its mechanism can provide more effective measures of prevention and treatment for APAP-induced liver injury. The aim of this study was to investigate whether toll-like receptor 4 (TLR4) participates in and regulates APAP-induced liver injury, which may provide a new direction for the prevention and treatment of clinical drug-induced hepatitis. WT mice were treated with APAP (300 mg/kg) or equivalent PBS. The livers of mice were taken at 1 h, 3 h, 6 h and 12 h after treatment. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect TLR4 mRNA expression level in the liver. After TLR4 involving in APAP-induced liver injury was confirmed, we investigated the relationship between TLR4 expression and hepatic inflammation. WT and TLR4-/- mice received APAP (3000 mg/kg) intraperitoneal injection after 16 h of fasting; serum was collected after 8 h and 24 h, and serum alanine aminotransferase (ALT) and reduced glutathione (GSH) activity were measured. Rat liver tissue was observed for histological changes by hematoxylin and eosin (H&E) staining. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) assay were performed to analyze proinflammatory cytokines expression (such as TNF-α, IL-1β, MCP-1, IL-6). After isolating mononuclear cells (MNCs) in the liver of mice, flow cytometry was used to detect cell activation level and infiltration of macrophages and neutrophils. Western blotting was used to analyze the activation of phosphorylated JNK and p38 signaling pathways in livers of WT and TLR4-/- mice. In addition, after stimulated with APAP, the silence of TLR4 in RAW264.7 cells could activate phosphorylated JNK and p38 signaling pathways. After APAP stimulation, WT mice exhibited more severe liver injury than TLR4-/- mice, with higher ALT levels, lower GSH levels, and more necrotic or apoptotic cells. TLR4-/- mice have lower levels of inflammatory cytokines including MCP-1 and IL-6; at the same time, the number of infiltrating macrophages and neutrophils in liver tissue of TLR4-/- mice was significantly lower than that of WT mice. The activation of JNK signaling pathway was strikingly enhanced in WT mice treated with APAP, but no significant difference was observed in the activation of JNK phosphorylation in TLR4-/- mice after the same dose of APAP stimulation. Similarly, in RAW264.7 cells, the activation of phosphorylated JNK and p38 was remarkably inhibited by TLR4-siRNA, but was activated in the control group, which was consistent in vivo. APAP-treated TLR4-/- mice showed milder liver injury compared to WT mice. It was confirmed that TLR4 could activate the JNK signaling pathway to induce the secretion of inflammatory factors and the infiltration of macrophages to promote APAP-induced liver injury. This finding might provide a new prevention and treatment idea for clinical drug-induced hepatitis.

The effect of short-term methionine restriction on glutathione synthetic capacity and antioxidant responses at the whole tissue and mitochondrial level in the rat liver.

Dietary methionine restriction (MR) where methionine is the sole source of sulfur amino acid increases lifespan in diverse species. Methionine restricted rodents experience a decrease in glutathione (GSH), a major antioxidant, in several tissues, which is paradoxical to longevity interventions because tissues with low GSH might experience more oxidative damage. Liver plays a key role in GSH synthesis and here we examined how MR influences GSH metabolism in the liver. We also hypothesised that low GSH might be subsidized by compensatory pathway(s) in the liver. To investigate GSH synthesis and antioxidant responses, Fischer-344 rats were given either a MR diet or a control diet for 8 weeks. Based on γ-glutamylcysteine synthetase activity, GSH synthetic capacity did not respond to low dietary methionine availability. Tissue level protein and lipid oxidation markers do not support elevated oxidative damage, despite low GSH availability. Whole tissue and mitochondrial level responses to MR differed. Specifically, the activity of glutathione reductase and thioredoxin reductase increase in whole liver tissue which might offset the effects of declined GSH availability whereas mitochondrial GSH levels were unperturbed by MR. Moreover, enhanced proton leak in liver mitochondria by MR (4 week) presumably diminishes ROS production. Taken together, we suggest that the effect of low GSH in liver tissue is subsidized, at least in part, by increased antioxidant activity and possibly by enhanced mitochondrial proton leak.

Uterine non-enzymatic antioxidant defence mechanisms (glutathione, vitamin C, copper and zinc) in diagnosis of canine pyometra.

The aim of the present study was to determine the concentrations of glutathione (GSH), vitamin C, copper (Cu) and zinc (Zn) in the uterine tissues in diagnosis of canine pyometra. Fourteen samples of uterine tissues from female dogs with pyometra and twelve samples of healthy uteruses (control) were used. The concentrations of GSH and vitamin C were determined in the uterine tissue homogenates using spectrophotometric methods. The concentrations of Cu and Zn were measured using atomic absorption spectrometer. The results obtained showed the significantly lower (p⟨0.05) concentration of GSH and the trend towards lower concentration of vitamin C in the pyometra samples compared to the control. The concentrations of Cu and Zn were similar in the uterine tissues from female dogs with pyometra and those from healthy female dogs. The lower GSH and vitamin C concentrations in the uterine tissues of female dogs with pyometra indicate that the non-enzymatic antioxidant mechanisms are impaired in the uterus of dogs with pyometra. These findings suggest that the imbalance of oxidative-antioxidative can play an important role in pathogenesis of canine pyometra.

A GSH-Gated DNA Nanodevice for Tumor-Specific Signal Amplification of microRNA and MR Imaging-Guided Theranostics.

Developing tumor-responsive diagnosis and therapy strategies for tumor theranostics is still a challenge owing to their high accuracy and specificity. Herein, an AND logic gated-DNA nanodevice, based on the fluorescence nucleic acid probe and polymer-modified MnO2 nanosheets, for glutathione (GSH)-gated miRNA-21 signal amplification and GSH-activated magnetic resonance (MR) imaging-guided chemodynamic therapy (CDT) is reported. In the presence of overexpressed miRNA and GSH (tumor cells), the nanodevice can be in situ activated and release significantly amplified fluorescence signals and MR signals. Conversely, the fluorescence signal is quenched and MR signal remains at the background level with low miRNA and GSH (normal cells), efficiently reducing the false-positive signals by more than 50%. Under the guide of miRNA profiling and MR imaging, the tumor-responsive hydroxyl radical (·OH) can effectively kill tumor cells. Furthermore, the nanodevice shows catalase-like activity and glucose oxidase-like activity with the performance of O2 production and glucose consumption. This is the first time to fabricate a tumor-responsive theranostic DNA nanodevice with tumor-specific signal amplification of microRNA and GSH-activated MR imaging for CDT, potential hypoxia relief and starvation therapy, which provides a new insight for designing smart theranostic strategies.

Insights into the interplay of latent toxoplasmosis, testosterone, cortisol and oxidative stress in screened schizophrenic patients in Egypt

Background: Toxoplasma gondii is a wide-spread infection. Most cases are asymptomatic latent toxoplasmosis and its link with schizophrenia is of wide interest. Toxoplasmosis induces immunopathological and neuroendocrine alterations that induce activation of hypothalamic pituitary-adrenal axis resulting in higher glucocorticoid and testosterone levels. Oxidative stress also has a role since antioxidants as glutathione (GSH) were found to be reduced. Objective: To assess seroprevalence/serointensity of toxoplasmosis in schizophrenic patients in relation to the levels of testosterone, cortisol and GSH activity in order to evaluate these factors in the etiopathogenesis of schizophrenic patients harboring latent toxoplasmosis. Subjects and Methods: In this cross sectional case control study, 120 schizophrenic inpatients were compared with 120 individuals attending the outpatients’ clinics in the same age range, and after exclusion of schizophrenia. Schizophrenia was confirmed or excluded using positive and negative syndrome scale (PANSS). Levels of Toxoplasma IgG, free testosterone, cortisol and GSH were determined in both groups. Results: Statistical analysis revealed no differences between cases and controls as regard age, gender, contact with pets, and Toxoplasma IgG seroprevalence. Toxoplasma IgG seroprevalence was higher in males compared to females and in rural areas than in urban areas. In Toxoplasma-positive patients, testosterone was higher in both genders and glutathione was lower, while no significant difference was documented in relation to PANSS, treatment with electroconvulsive-therapy (ECT) or cortisol level. Schizophrenic patients showed higher Toxoplasma antibody titer, cortisol, free testosterone levels in both genders and lower GSH than control. Male schizophrenic patients particularly showed lower GSH level and higher Toxoplasma antibody titer. Free testosterone level was significantly higher in male patients who had received ECT. Conclusion: Latent toxoplasmosis may be involved in the etiology of schizophrenia. Screening and treatment of toxoplasmosis is advisable to prevent schizophrenia. Also, screening of schizophrenic patients for chronic toxoplasmosis and the fore mentioned parameters is recommended for prediction of complications and presents a promising approach for prevention and management.

Correlation of NLR with Oxidative Stress Markers in Sickle Cell Anemia with Vasoocclusive Crisis

&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Introduction&#x0D; Sickle cell disease has long been recognized as an inflammatory condition and oxidative stress play an important role in pathophysiology of SCD. Several biomarkers have been associated with SCA clinical prognosis. This study was designed to determine the oxidative stress &amp; inflammatory biomarker that can be used in monitoring the prognosis &amp; management of SCA patients.&#x0D; Aim &amp; Objective&#x0D; The present study is aimed to assess the role of NLR along with CRP, MDA and erythrocyte GSH in vaso-occlusive (HbSS) crisis patients compared to steady state (HbSS) patients.&#x0D; Materials &amp; Method&#x0D; A total of 100 sickle cell anemia patients aged between 20–40 years of either sex were evaluated and divided into 2 groups. Group A-sickle cell anemia patients with vasoocclusive crisis(N=50) Group B-sickle cell anemia patients with steady state as control group(N=50). We analysed the oxidative stress marker i.e. reduced glutathione (GSH) &amp; MDA along with inflammatory markers NLR, CRP and compared between both A&amp; B groups.&#x0D; Result&#x0D; The Unpaired t test between A &amp; B group shows significant increase in NLR, MDA, CRP Level in VOC patients as compared to steady state sickle cell patients(P?0.05). Compared with values of controls, SCA subjects with VOC had significantly lower erythrocyte GSH (P ?0.05). In the present study positive correlation of NLR with MDA and CRP in sickle cell anemia patient with vasoocclusive crisis is evaluated.&#x0D; Conclusion&#x0D; So the early prediction of vaso-occlusive crisis by the detection of the NLR count along with MDA, CRP, GSH level might be beneficial in the management sickle cell anemia patient. Additional studies are warranted to test this hypothesis.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Glutathione deficiency-elicited reprogramming of hepatic metabolism protects against alcohol-induced steatosis

Depletion of glutathione (GSH) is considered a critical pathogenic event promoting alcohol-induced lipotoxicity. We recently show that systemic GSH deficiency in mice harboring a global disruption of the glutamate-cysteine ligase modifier subunit (Gclm) gene confers protection against alcohol-induced steatosis. While several molecular pathways have been linked to the observed hepatic protection, including nuclear factor erythroid 2-related factor 2 and AMP-activated protein kinase pathways, the precise mechanisms are yet to be defined. In this study, to gain insights into the molecular mechanisms underpinning the protective effects of loss of GCLM, global profiling of hepatic polar metabolites combined with liver microarray analysis was carried out. These inter-omics analyses revealed both low GSH- and alcohol-driven changes in multiple cellular pathways involving the metabolism of amino acids, fatty acid, glucose and nucleic acids. Notably, several metabolic changes were uniquely present in alcohol-treated Gclm-null mouse livers, including acetyl-CoA enrichment and diversion of acetyl-CoA flux from lipogenesis to alterative metabolic pathways, elevation in glutamate concentration, and induction of the glucuronate pathway and nucleotide biosynthesis. These metabolic features reflect low GSH-elicited cellular response to chronic alcohol exposure, which is beneficial for the maintenance of hepatic redox and metabolic homeostasis. The current study indicates that fine-tuning of hepatic GSH pool may evoke metabolic reprogramming to cope with alcohol-induced cellular stress.