GSSG Levels Research Articles

Chemical and Green ZnO nanoparticles ameliorated adverse effects of cisplatin on histological structure, antioxidant defense system and neurotrophins expression in rat hippocampus

Cisplatin (CP) is a chemotherapy agent used in the treatment of cancer, but it has various side effects, in particular, neurotoxicity. Zinc oxide nanoparticles (ZnO NPs) are a potent antioxidant. However, there is limited knowledge about the protective effects of ZnO NPs against CP-induced hippocampal toxicity. The present study aimed to explore the potential protective effects of ZnO NPs against CP-induced oxidative stress, loss of neurotrophins support, and tissue damage in the hippocampus of the rats. Eighty adult male Wistar rats were dividing into ten groups including: control (Con), sham, ZnO Bulk (ZnB), chemical ZnO NPs (ChZnO NPs), Green ZnO NPs (GrZnO NPs), CP, CP + ZnB, CP + ChZnO NPs, CP + GrZnO NPs and CP + AE. CP was administrated (5 mg/kg/weekly) for four weeks, and animals were treated simultaneously with different forms of ZnO (5 mg/kg/day). At the end of the experiment, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), changes of reduced glutathione (GSH), oxidized glutathione (GSSG) and GSH/GSSG ratio, histological changes, expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) genes were assessed in the hippocampus. The results revealed that a decrease in BDNF and NGF mRNA expression, GSH concentration and GSH/GSSG ratio, increasing of GSSG and MDA levels, and neuronal loss in the CP-treated rats were reversed following the administration of different forms of ZnO, especially Gr ZnO NPs and ch ZnO NPs. Co-administration of ZnO NPs to CP-treated rats restored the suppressive effects of CP on activities of antioxidant enzymes (SOD, GPX, CAT). The results showed that in most of the evaluated factors, Gr ZnO NPs showed a greater protective effect than other forms of ZnO. The results suggest that ZnO NPs, in particular Green ZnO NPs (GrZnO NPs) had more potential protective effects against CP-induced oxidative stress, inadequate support neurotrophin and tissue damage in rat hippocampus.

Swimming exercise attenuates anxiety-like behavior by reducing brain oxidative stress in type 2 diabetic mice

Anxiety-related behaviors are among the most prevalent psychiatric disorders in patients with type 2 diabetes (T2D). The protective effect of exercise on neuropsychiatric disorders has been documented. However, there are no studies that examined whether swimming exercise can decrease anxiety-like symptoms in type 2 diabetes. We investigated the effects of swimming exercise on body weight, anxiety-like behavior, glucose and insulin levels, and brain oxidative stress in male C57BL/6 mice. T2D-induced mice were subjected to swimming exercise, then anxiety-like behaviors were measured by the open field, light-dark box, and elevated plus-maze tests. Glucose and insulin levels were measure in serum, and antioxidant/oxidative markers including glutathione (GSH), malondialdehyde (MDA), and glutathione disulfide (GSSG) were measured in the brain. Our findings showed that T2D increased body weight, anxiety-like symptoms, glucose and insulin resistance, and oxidative stress by increasing MDA and GSSG levels in the brain of mice. Interestingly, swimming exercise reversed these parameters in diabetic mice. Our findings clearly indicate that there is a protective impact of swimming exercise on anxiety-like behavior by reducing insulin resistance and brain oxidative stress in mice with type 2 diabetes. Further studies are needed to validate these findings in humans.

Apple leaves and their major secondary metabolite phlorizin exhibit distinct neuroprotective activities: Evidence from in vivo and in silico studies

Apple, Malus domestica Borkh., a fruit-producing and medicinal plant, is reported to have a wide array of biological effects including a neuroprotective potential. In this work, the phytochemical composition of the leaf extract from M. domestica was thoroughly investigated using LC-MS/MS. Phlorizin, the major secondary metabolite was also isolated and characterized using MS and NMR data. Total phenolic content (TPC) and the total flavonoid content (TFC) were determined. The in vivo neuroprotective effect of the extract and its major component phlorizin was evaluated in rats using the novel object recognition (NOR) test. The antioxidant activity of the extract and phlorizin was evaluated in vitro by the well-known DPPH assay and in vivo through determining the total antioxidant capacity (TAC), and some oxidative stress parameters such as the reduced and oxidized glutathione (GSH, GSSG) respectively and the lipid peroxidation marker (MDA) in rats previously treated with dexamethasone (10 mg/kg i.p.) daily for 9 days and the tropane alkaloid scopolamine (1 mg/kg. i.p.) for 2 consecutive days (day 7 and 8). Moreover, the extract and phlorizin were tested to block the activity of β-secretase (BACE1) that is involved in the formation of amyloid-β (Aβ) plaques in silico and in vivo, an important player in the pathogenesis of Alzheimer’s disease. Molecular docking was performed to confirm the potential of phlorizin and other individual components of the extract to bind to and block BACE1. The extract and phlorizin revealed substantial antioxidant potential with IC50 of 6.93 and 5.14 µg/mL, respectively in DPPH assay. They were able to significantly restore TAC, increase GSH, and reduce both GSSG and MDA levels in the dexamethasone/scopolamine treated rats. Both extract and phlorizin were able to inhibit BACE1 with IC50 of 1.65 and 1.18 µg/mL, respectively. Our results provide evidence that M. domestica and its major secondary metabolite phlorizin are promising neuroprotective natural agents for treating Alzheimer Disease and other neurodegenerative disorders especially recognition impairment disorders. More studies are needed to elaborate the mechanism of action.

N-METHYL-D-ASPARTATE RECEPTOR INHIBITION PREVENTS GLUCOMETABOLIC DYSREGULATION AND CARDIAC INJURY IN NICOTINE-EXPOSED MALE RATS

Objective: Since non-smoking nicotine exposure has been associated with cardiometabolic disorders and smoking cessation therapies are of great global and medical significance. N-methyl-D-aspartate receptor (NMDAR) activity has been implicated in diabetes. Although NMDAR is also expressed in cardiomyocytes, there is dearth of information on its activity on cardiometabolic dysfunctions and its associated mechanism yet to be fully elucidated. It is therefore hypothesized that NMDAR inhibition by low-dose ketamine would improve nicotine-induced glucometabolic deregulation and cardiac injury. Design and method: Male Wistar rats (n = 6/group) aged 10 weeks were given (p.o.) vehicle, nicotine (1.0 mg/kg) with or without ketamine (0.2 mg/kg) daily for 28 days. Oral glucose tolerance test was performed 24-hours to the end of the experiment. The insulin resistance was estimated using the homeostasis model assessment for insulin resistance (HOMA-IR). Results: Data showed that nicotine exposure led to insulin resistance, hyperinsulinemia, elevated 1-hour postload glucose, glucose intolerance, triglyceride-glucose index. Likewise, plasma and cardiac uric acid, malondialdehyde, lactate, triglyceride (TG), TG/HDL-C, oxidized glutathione (GSSG) levels, creatinine kinase (CK), lactate dehydrogenase (LDH), adenosine deaminase (ADA), xanthine oxidase (XO) activities were increased in nicotine-exposed rats. On the other hand, plasma and cardiac nitric oxide level was reduced by nicotine exposure. However, ketamine treatment also led to elevated TG, LDH, lactate, CK activity, nitric oxide, and reduced TG/HDL-C, uric acid, MDA, GSSG levels, XO and ADA activities when compared to control. However, these nicotine-induced cardiometabolic disorders were ameliorated in ketamine-treated rats. Conclusions: The results demonstrated that low-dose ketamine prevents glucose dysregulation, plasma and cardiac TG, uric acid, lactate accumulation and suppressed ADA, XO and CK activities. Therefore, these findings imply that inhibition of NMDAR by low dose-ketamine improves glucometabolic regulation and ameliorates cardiac injury through ADA/XO/CK-dependent mechanisms.

L-Glutamine Supplementation Enhances Strength and Power of Knee Muscles and Improves Glycemia Control and Plasma Redox Balance in Exercising Elderly Women.

We investigated the effects of oral L-glutamine (Gln) supplementation, associated or not with physical exercises, in control of glycemia, oxidative stress, and strength/power of knee muscles in elderly women. Physically active (n = 21) and sedentary (n = 23) elderly women aged 60 to 80 years were enrolled in the study. Plasma levels of D-fructosamine, insulin, reduced (GSH) and oxidized (GSSG) glutathione, iron, uric acid, and thiobarbituric acid-reactive substances (TBARs) (lipoperoxidation product), as well as knee extensor/flexor muscle torque peak and average power (isokinetic test), were assessed pre- and post-supplementation with Gln or placebo (30 days). Higher plasma D-fructosamine, insulin, and iron levels, and lower strength/power of knee muscles were found pre-supplementation in the NPE group than in the PE group. Post-supplementation, Gln subgroups showed higher levels of GSH, GSSG, and torque peak, besides lower D-fructosamine than pre-supplementation values. Higher muscle average power and plasma uric acid levels were reported in the PE + Gln group, whereas lower insulin levels were found in the NPE + Gln than pre-supplementation values. TBARs levels were diminished post-supplementation in all groups. Gln supplementation, mainly when associated with physical exercises, improves strength and power of knee muscles and glycemia control, besides boosting plasma antioxidant capacity of elderly women.

Electromagnetic Fields Ameliorate Insulin Resistance and Hepatic Steatosis by Modulating Redox Homeostasis and SREBP-1c Expression in db/db Mice.

PurposeThe prevalence of nonalcoholic fatty liver disease (NAFLD), which has recently become known as metabolic-associated fatty liver disease (MAFLD), has risen. However, pharmacotherapies for this disease have not been approved. Electromagnetic fields (EMFs) have excellent bioeffects on multiple diseases. However, the effects of EMFs on NAFLD are unknown. This study investigated the bioeffects of EMF exposure on insulin resistance, liver redox homeostasis and hepatic steatosis in db/db mice.MethodsAnimals were sacrificed after EMF exposure for 8 weeks. The fasting blood glucose and insulin levels in the serum were tested. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated by a formula. The levels of MDA, GSSG and GSH, biomarkers of redox, were assessed. The activities of CAT, SOD and GSH-Px were assessed. The body and liver weights were measured. Hepatic lipid accumulation was observed by Oil Red O staining. Hepatic CAT, GR, GSH-Px, SOD1, SOD2 and SREBP-1 expression was determined by Western blotting.ResultsEMF exposure ameliorated insulin resistance and oxidative stress in the liver by downregulating the MDA and GSSG levels, increasing the reduced GSH levels, and promoting the GSH-Px levels in db/db mice. In addition, liver weight and triglyceride (TG) levels were reduced by EMF exposure. Simultaneously, EMF exposure improved hepatic steatosis by downregulating the protein expression of SREBP-1c.ConclusionThe present findings suggest that EMF exposure has positive effects in the treatment of NAFLD.

Alterations in glutathione redox homeostasis among adolescents with obesity and anemia

The reduced (GSH)-to-oxidized (GSSG) glutathione ratio represents a dynamic balance between oxidants and antioxidants. However, redox status in adolescents with obesity and anemia has not been investigated. This study investigated the association of erythrocyte GSH redox status (GSH, GSH:GSSG ratio, and glutathione peroxidase [GPx] activity) with anemia and adiposity in adolescents. This case–control study nested in a cross-sectional study enrolled 524 adolescents (268 boys; 256 girls). The prevalence of anemia in overweight and obesity (OWOB) was 5.2% in boys and 11.7% in girls. The GSH:GSSG ratio and GPx activity were significantly higher in girls than in boys (p < 0.001), in anemic than in non-anemic subjects (p < 0.001), and in OWOB than in normal-weight subjects (p < 0.001). Similarly, significantly higher GSH: GSSG level (p < 0.001) and GPx activity (p < 0.001) were found in subjects with 90th percentile waist circumference than in those with < 90th percentile. GPx and GSH:GSSG were positively associated with anemia after adjusting for age, sex, and body mass index (adjusted odds ratio, adjOR [95% confidence interval, CI] 2.18 [1.44–3.29]) or tertiles (adjOR [95% CI], T3 = 2.49 [1.03–6.01]). A similar association was noted for GSH and GPx. A compensatory increased redox defense mechanism exists in anemia and obesity among adolescents without metabolic disturbances.

Embryonic zebrafish response to a commercial formulation of azoxystrobin at environmental concentrations

Azoxystrobin is a broad-spectrum strobilurin fungicide for use on a wide range of crops available to end-users as formulated products. Due to its extensive application, it has been detected in aquatic ecosystems, raising concerns about its environmental impact, which is still poorly explored. The objective of this work was to study the effects of a commercial formulation of azoxystrobin in the zebrafish embryo model. Sublethal and lethal effects were monitored during the exposure period from 2 h post fertilisation (hpf) to 96 hpf after exposure to azoxystrobin concentrations (1, 10 and 100 μg L−1). The responses of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR)) as well as detoxifying enzymes (glutathione-s-transferase (GST) and carboxylesterase (CarE)) were evaluated at 96 hpf. Similarly, glutathione levels (reduced (GSH) and oxidised (GSSG) glutathione), neurotransmission (acetylcholinesterase (AChE)) and anaerobic respiration (lactate dehydrogenase (LDH)) -related enzymes were assayed. At 120 hpf, larvae from each group were used for behaviour analysis. Results from this study showed concentration-dependent teratogenic effects, particularly by increasing the number of malformations (yolk and eye), with a higher prevalence at the highest concentration. However, it was found that the lowest concentration induced a high generation of reactive oxygen species (ROS) and increased activity of SOD, GST, and CarE. In addition, GR and GSSG levels were decreased by the lowest concentration, suggesting an adaptive response to oxidative stress, which is also supported by the increased AChE activity and absence of behavioural changes. These findings advance the knowledge of the azoxystrobin developmental and environmental impacts, which may impose ecotoxicological risks to non-target species.

Redox forms of glutathione in malignant lesions of the stomach with varying aggressiveness degrees

Aim. To study the levels of reduced and oxidized glutathione (GSH and GSSG, respectively), as well as the thiol status in gastric cancer (GC) tumors of various histological types and grades. Materials and methods. The indicators were determined by ELISA methods in tumor, peritumoral and visually intact tissues obtained during surgery from 52 patients with GC: 18 patients had a G1-2 adenocarcinoma (AC), 8 with G3 AC, 6 with signet ring cell cancer (SRCC), 14 with combined gastric lesions (CGL) – AC with signet ring cell fragments, 6 with patients with a component of undifferentiated cancer, G4. Results. In the groups of patients with low-differentiated and undifferentiated tumors, the GSH content in the tumor tissue and the peritumoral zone was higher than in the group of patients with well- and moderately-differentiated tumors. Tumor GSH levels in G3 AC and SRCC exceeded the values in visually intact tissues. Moreover, in the visually intact tissue of patients with SRCC, GSH level was reduced relative to G1-2 AC and CGL. GSH in all tissues of patients with CGL was higher than in patients with G1-2 AC. The lowest level of GSSG in the tumor tissue was registered in SRCC: 27.5% lower than in G1-2 AC and 30.3% lower than in G3 AC. Patients with undifferentiated tumors (G4 AC) had the highest GSH content in all studied tissues: by 29.9% in tumor; by 40.7% in peritumoral zone; and in visually intact tissue not only GSH, but also GSSG was increased by 22.5–25.5% in comparison with AC G1-2. G4 AC was also characterized by a sharp increase in the thiol status in tumor tissues by 80.2 and 89.9% higher than in visually intact and peritumoral tissues, and it was statistically higher than in AC G1-2, AC G3, SRCC and CGL. The ratio of GSH and GSSG was the most informative. Conclusion . Poor AC differentiation (in the row G1-2, G3, G4) and a change of histological tumor type (AC, SPL and SRCC), i.e. an increase in tumor aggressiveness, were accompanied by the enhancement of reductive processes in tumor tissue, as evidenced by the statistically significant increase in the GSH/GSSG coefficient and a sharp increase in the thiol status in G4 AC.

Urtica dioica extracts abolish scopolamine-induced neuropathies in rats.

Alzheimer's disease (AD) is characterized by alterations in monoamines, oxidative stress, and metabolic dysfunctions. We aim to assess the therapeutic impacts of roots or leaf extract from Urtica dioica (UD; stinging nettle) against scopolamine (SCOP)-induced memory dysfunction, amnesia, and oxidative stress in rats. Spatial memory was assessed by Y maze test. Tissue analyses of norepinephrine (NE), dopamine (DA), serotonin (5-HT), malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH, GSSG), AMP, ADP, and ATP were assessed by HPLC. mRNA levels of Tau and Hsp70 were estimated by PCR. UD extracts particularly nettle root (NR) significantly normalized the SCOP-induced memory deficits even more potent than sermion (SR) and donepezil (DON). Similarly, NR had potent therapeutic impacts on the levels of cortical and hippocampal monoamines e.g. DA, NE, and 5-HT. SCOP induced a dramatic oxidative stress as measured by MDA, NO, and GSSG levels; however, UD extracts showed significant anti-oxidative stress impacts. Additionally, UD extracts restored ATP levels and reduced the levels of AMP and ADP compared to SCOP-treated rats. Furthermore, cortical Tau and hippocampal Hsp70 were modulated by UD extracts particularly NR compared to the SCOP group. In conclusion, UD extracts particularly roots have potential therapeutic impacts against SCOP-induced neuroinflammatory and/or Alzheimer-like phenotype in rats.

Biochemical changes and antioxidant capacity of naringin and naringenin against malathion toxicity in Saccharomyces cerevisiae

Flavonoids are rich in seeds, citrus fruits, olive oil, tea and red wine. Citrus flavonoids constitute an important type of flavonoids. Naringin and naringenin belong to flavonoids with known antioxidant and were found to display antioxidant activities. Malathion is an organophosphorus pesticide that has been broadly used throughout the world to control weeds and pests. It has also been used in public health for mosquito control and fruit fly eradication programs. Malathion, naringin, and naringenin were added to be in 40, 80, and 160 mg doses in Saccharomyces cerevisiae cultures mainly used to determine the antioxidant capacity, it is known that they have shown similar results to man. At the end of the experiment, total protein, malondialdehyde (MDA), reduced glutathione (GSH), oxidized glutathione (GSSG), vitamin K, vitamin E, vitamin D, ergosterol, stigmasterol, β-Sitosterol, and fatty acids were analyzed by HPLC (high performance liquid chromatography) and GC (gas chromatography) devices in the tested S. cerevisiae samples. The contents of the yeast cell of octanoic acid (C8:0), lauric acid (C12:0), myristic acid (C14:0), palmitic acid (C16:0), palmitoleic acid (C16:1n-7), heptadecanoic acid (C17:0), stearic acid (C18:0), oleic acid (C18:1n-9), and linoleic acid (C18:2n-6) were identified. There were statistically significant changes in total protein, MDA, GSH, GSSG, vitamin K, vitamin E, vitamin D, phytosterol and fatty acid levels. It was determined that naringin and naringenin showed statistically significant decreases against malathion toxicity on these parameters. From this study it is found that, the mitigating effect of naringin against DPPH stable free radical was higher than that of naringenin. Citrus flavonoid, naringin showed promising antioxidant activity which can be used as effective protecting agents against oxidative stress.

Hepatoprotective effect of galangin on carbon tetrachloride-induced hepatotoxicity via the LKB1/AMPK pathway

To investigate the protective effects of galangin on liver toxicity induced by carbon tetrachloride (CCl4) in mice. Mouse hepatotoxicity model was established by intraperitoneal injection (i.p.) of 10 ml/kg body weight CCl4 that diluted with corn oil to a proportion of 1:500 on Kunming mice. The mice were randomly divided into five groups named control group, model group, and 1, 5, and 10 mg/kg galangin group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. Liver histopathological examination was observed via optical microscopy. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and glutathion (GSSG) were analyzed to assess oxidative stress. Finally, western blot assay was carried out to analyse the expression levels of total AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), total liver kinase B1 (LKB1), and phospho-LKB1 (p-LKB1). Compared with the control group, in the model group, the levels of AST, ALT, MDA, and GSSG increased significantly ( p &lt; 0.01); the activity of SOD and GSH decreased significantly ( p &lt; 0.01); and the histopathological examination revealed liver necrosis. However, treatment with galangin (5 and 10 mg/kg) significantly reversed these CCl4-induced liver damage indicators. Furthermore, treatment with galangin (10 mg/kg) significantly increased the p-AMPK and p-LKB1 expression levels ( p &lt; 0.01). This study supports the hepatoprotective effect of galangin against hepatotoxicity, perhaps occurring mainly through the LKB1/AMPK-mediated pathway.

Fecal Microbiota Transplantation Is a Promising Method to Restore Gut Microbiota Dysbiosis and Relieve Neurological Deficits after Traumatic Brain Injury.

Background Traumatic brain injury (TBI) can induce persistent fluctuation in the gut microbiota makeup and abundance. The present study is aimed at determining whether fecal microbiota transplantation (FMT) can rescue microbiota changes and ameliorate neurological deficits after TBI in rats. Methods A controlled cortical impact (CCI) model was used to simulate TBI in male Sprague-Dawley rats, and FMT was performed for 7 consecutive days. 16S ribosomal RNA (rRNA) sequencing of fecal samples was performed to analyze the effects of FMT on gut microbiota. Modified neurological severity score and Morris water maze were used to evaluate neurobehavioral functions. Metabolomics was used to screen differential metabolites from the rat serum and ipsilateral brains. The oxidative stress indices were measured in the brain. Results TBI induced significance changes in the gut microbiome, including the alpha- and beta-bacterial diversity, as well as the microbiome composition at 8 days after TBI. On the other hand, FMT could rescue these changes and relieve neurological deficits after TBI. Metabolomics results showed that the level of trimethylamine (TMA) in feces and the level of trimethylamine N-oxide (TMAO) in the ipsilateral brain and serum was increased after TBI, while FMT decreased TMA levels in the feces, and TMAO levels in the ipsilateral brain and serum. Antioxidant enzyme methionine sulfoxide reductase A (MsrA) in the ipsilateral hippocampus was decreased after TBI but increased after FMT. In addition, FMT elevated SOD and CAT activities and GSH/GSSG ratio and diminished ROS, GSSG, and MDA levels in the ipsilateral hippocampus after TBI. Conclusions FMT can restore gut microbiota dysbiosis and relieve neurological deficits possibly through the TMA-TMAO-MsrA signaling pathway after TBI.

Parthenolide Induces Oxidative Stress and Impedes Cell Migration by Suppressing Wnt Pathway and Epithelial-Mesenchymal-Transition (EMT) in HCT-116 Metastatic Colorectal Cancer Cells

Colorectal cancer (CRC) is a vital cause of cancer morbidity and mortality. 50% of CRC patients suffer from an aggressive metastatic disease which ultimately fallout in death. In metastatic cancer, tumour cells migrate, invade, and finally colonise to the distant organ by degrading their attachments with the extracellular matrix. Parthenolide (PTL) is a secondary metabolite of feverfew (Tanacetum parthenium) plant. It shows its cytotoxic effect towards cancer cells via different cellular signalling pathways like inhibition of NF-κB, STAT3, MAPK, JNK pathways, activation of p53 etc. In the present study, we have assessed anti-cancer and anti-metastatic potential of PTL against human HCT-116 metastatic colorectal cancer cells. Analysis of cellular oxidative status (GSH/GSSG) of PTL treated HCT-116 cells showed a significant decrease (p&lt;0.05) in GSH level while GSSG level was increased significantly (p&lt;0.05) on PTL treatment. PTL also increased the amount of intracellular reactive oxygen species. The qRT-PCR analysis revealed that PTL down-regulates c-fos, c-jun and N-cadherin expression and up-regulates E-cadherin expression indicating inhibition of cell migration and metastasis by EMT pathway. PTL inhibited the MMP-9 expression in a dose-dependent fashion and inhibited cancer cell migration by regulating Wnt/β-catenin signalling through the up-regulation of DKK-1 protein expression indicating PTL has a promising anti-cancer potential against HCT-116 metastatic colorectal carcinoma cells.

Insulin Resistance and Oxidative Stress: In Relation to Cognitive Function and Psychopathology in Drug-Naïve, First-Episode Drug-Free Schizophrenia.

Objective: The present study aimed to examine whether insulin resistance and oxidative stress are associated with cognitive impairment in first-episode drug-free schizophrenia (SZ) patients.Methods: Ninety first-episode SZ patients and 70 healthy controls were enrolled. Fasting insulin (FINS) and markers of oxidative stress [oxidized glutathione (GSSG), superoxide dismutase (SOD), nitric oxide (NO) and uric acid (UA) levels] were measured in serum before pharmacological treatment was initiated. Psychiatric symptoms and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB), respectively. In addition, the homeostatic model assessment of insulin resistance (HOMA-IR) was also studied.Results: HOMA-IR and serum levels of GSSG and NO were significantly higher in SZ patients than in healthy controls (P < 0.001), while the serum levels of SOD were significantly lower than in healthy controls (P < 0.001). HOMA-IR, GSSG and NO levels were significantly correlated to the total cognitive function scores of the patient group (r = −0.345,−0.369,−0.444, respectively, P < 0.05). But these factors were not co-related to the cognitive functions in the healthy control group. And, levels of SOD, UA were not associated with the total cognitive function scores in both the patient and the healthy control groups. NO was positively correlated with general pathological and the total score in the PANSS, and was negatively correlated with six cognitive domains (r = −0.316 to −0.553, P < 0.05).Conclusions: The levels of insulin resistance and oxidative stress are elevated, and correlated with the severity of cognitive impairment in drug-naïve, first-episode SZ patients. Treatment approaches targeting on reducing insulin resistance and oxidative stress may improve cognitive function in SZ patients.

The Relationship between Choroidal Thickness and Intracellular Oxidised-reduced Glutathione and Extracellular Thiol–disulfide Homeostasis at Different Stages of Diabetic Retinopathy

ABSTRACT Purpose: To evaluate the relationship between diabetic retinopathy and oxidative damage by measuring intracellular and extracellular thiol levels, and to compare intracellular and extracellular thiol levels. Method: In this prospective, cross-sectional, and comparative study, 25 healthy control participants (group 1), a total of 25 diabetic macular edema (DME) patients with non-proliferative diabetic retinopathy (DRP) and without DME (group 2), and 25 DME patients with non-proliferative DRP and with DME (group 3) were included. Choroidal thickness (ChT) and central macular thickness (CMT) were measured by spectral domain optic coherence tomography. For the evaluation of antioxidant/oxidant balance, intracellular GSH (reduced glutathione) and GSSG (oxidized glutathione), extracellular SH (thiol) and SS (disulfide) levels were measured and recorded. Results: Comparing intracellular and extracellular thiol levels between groups, intracellular GSSG level and GSSG/GSH percent ratio, and extracellular disulfide and SS/SH percent ratio values were higher in diabetic patients than healthy participants. Choroidal thicknesses were significantly thinner in DRP groups compared to the healthy population. When the relationship between choroidal thicknesses and thiol levels was investigated, there were significant relationships between choroidal thicknesses and thiol levels in group 3. Conclusion: Oxidative stress and impaired intracellular GSH/GSSG and serum SH/SS balances were observed to have an effect on DRP and DME pathogenesis. In addition, in groups with and without DME, thinning in choroidal thicknesses and the relationship between these thicknesses and intra/extracellular oxidative stress indicators can also be explained.

Oxidative status and changes in the adenosine deaminase activity in experimental host infected with tropical liver fluke, Fasciola gigantica

Fine tuning of the metabolic, physiological and immunological cues along with interplay between the biomolecules of the host and the parasite could be responsible for the successful establishment of parasitic infections. The present investigation was aimed at evaluating the oxidative status and the level of adenosine deaminase (ADA) in the serum and liver of rabbits experimentally infected with Fasciola gigantica. A significant increase in level of ROS, MDA and 4-HNE along with a decline in the SOD, CAT, GR and GST activity was evident in rabbits experimentally infected with Fasciola gigantica. However, there was an increase in the GPX activity in the sera of infected rabbits. The increased GPX activity and decreased GR activity would have resulted in the depletion of GSH, a key non-enzymatic antioxidant, in the infected animals. The level of GSSG was also found to be higher in the sera and liver tissues of the infected rabbits along with a decline in the GSH/GSSG ratio, indicating a high level of oxidative stress in the infected animals, which also showed a significant increase in the activity of the marker enzymes of liver pathology, AST and ALT. Further, a significant inhibition of the adenosine deaminase (ADA) activity in the infected rabbits was accompanied with the reduction in the level of pro-inflammatory cytokine, IL-6 while the anti-inflammatory cytokine, IL-4 level was significantly elevated.In conclusion, the F. gigantica induced significant oxidative stress as evident from the increased levels of ROS and lipid peroxidation along with the disruption of antioxidant and detoxification cascade ultimately lead to pathogenic and inflammatory responses in the experimental host. Whereas, the altered ADA activity could modulate the host's immune responses toward Th-2 type and would facilitate the successful establishment of flukes within their host, thus indicating that ADA could be exploited as a target for the development of novel anthelmintic drugs against fasciolosis.

Investigation of some biochemical parameters of wild and cultured Myrtus communis L. fruits subjected to different conservation methods

In this study, wild and cultivated white Myrtus communis L. (“myrtle”) fruits were investigated for their vitamin levels (A, B, C and E), carotenes (lycopene, β-carotene), functional peptides (glutathione, ghrelin), oxidative stress markers (GSSG and MDA), total phenolic and flavonoid substances, antioxidant capacity (DPPH, TEAC) and essential elements (Se, Zn, Fe, Cu and Mn). The results showed that both myrtle fruits can be considered as the good source of vitamins, antioxidants and elements. The preservation (sun or microwave-drying) methods for this seasonal fruit caused a significant (p < 0.05) decrease in their biochemical and bio-pharmacological content compared to fresh or frozen fruits. On the contrary, preservation resulted a significant increase in GSSG and MDA levels. The amounts of Se, Zn, Fe, Cu and Mn in wild myrtle fruit were found as 0.58, 205, 228.0, 37.22 and 24.3 µg/g dw, respectively.

Exposure of Rats to Multiple Oral Doses of Dichloroacetate Results in Upregulation of Hepatic Glutathione Transferases and NAD(P)H Dehydrogenase [Quinone] 1.

Dichloroacetate (DCA) is an investigational drug that is used in the treatment of various congenital and acquired disorders of energy metabolism. Although DCA is generally well tolerated, some patients experience peripheral neuropathy, a side effect more common in adults than children. Repetitive DCA dosing causes downregulation of its metabolizing enzyme, glutathione transferase zeta 1 (GSTZ1), which is also critical in the detoxification of maleylacetoacetate and maleylacetone. GSTZ1 (-/-) knockout mice show upregulation of glutathione transferases (GSTs) and antioxidant enzymes as well as an increase in the ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH), suggesting GSTZ1 deficiency causes oxidative stress. We hypothesized that DCA-mediated depletion of GSTZ1 causes oxidative stress and used the rat to examine induction of GSTs and antioxidant enzymes after repeated DCA exposure. We determined the expression of alpha, mu, pi, and omega class GSTs, NAD(P)H dehydrogenase [quinone] 1 (NQO1), gamma-glutamylcysteine ligase complex (GCLC), and glutathione synthetase (GSS). GSH and GSSG levels were measured by liquid chromatography-tandem mass spectrometry. Enzyme activity was measured in hepatic cytosol using 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene, and 2,6-dichloroindophenol as substrates. In comparison with acetate-treated controls, DCA dosing increased the relative expression of GSTA1/A2 irrespective of rodent age, whereas only adults displayed higher levels of GSTM1 and GSTO1. NQO1 expression and activity were higher in juveniles after DCA dosing. GSH concentrations were increased by DCA in adults, but the GSH:GSSG ratio was not changed. Levels of GCLC and GSS were higher and lower, respectively, in adults treated with DCA. We conclude that DCA-mediated depletion of GSTZ1 causes oxidative stress and promotes the induction of antioxidant enzymes that may vary between age groups. SIGNIFICANCE STATEMENT: Treatment with the investigational drug, dichloroacetate (DCA), results in loss of glutathione transferase zeta 1 (GSTZ1) and subsequent increases in body burden of the electrophilic tyrosine metabolites, maleylacetoacetate and maleylacetone. Loss of GSTZ1 in genetically modified mice is associated with induction of glutathione transferases and alteration of the ratio of oxidized to reduced glutathione. Therefore, we determined whether pharmacological depletion of GSTZ1 through repeat administration of DCA produced similar changes in the liver, which could affect responses to other drugs and toxicants.

A high magnesium concentration in citrate dialysate prevents oxidative stress and damage in human monocytes in vitro.

BackgroundThe use of dialysis fluids (DFs) during haemodialysis has been associated with increased oxidative stress and reduced serum magnesium (Mg) levels, contributing to chronic inflammation. Since the role of Mg in modulating immune function and reducing oxidative stress has been demonstrated, the aim of this study was to characterize in vitro whether increasing the Mg concentration in DFs could protect immune cells from oxidative stress and damage.MethodsThe effect of citrate [citrate dialysis fluid (CDF), 1 mM] or acetate [acetate dialysis fluid (ADF), 3 mM] dialysates with low (0.5 mM; routinely used) or high (1 mM, 1.25 mM and 2 mM) Mg concentrations was assessed in THP-1 human monocytes. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and oxidized/reduced (GSSG/GSH) glutathione were quantified under basal and inflammatory conditions (stimulation with lipopolysaccharide, LPS).ResultsThe increase of Mg in CDF resulted in a significant reduction of ROS production under basal and inflammatory conditions (extremely marked in 2 mM Mg; P < 0.001). These effects were not observed in ADF. Interestingly, in a dose-dependent manner, high Mg doses in CDF reduced oxidative stress in monocytes under both basal and inflammatory conditions. In fact, 2 mM Mg significantly decreased the levels of GSH, GSSG and MDA and the GSSG/GSH ratio in relation to 0.5 mM Mg.ConclusionsCDF produces lower oxidative stress than ADF. The increase of Mg content in DFs, especially in CDF, could have a positive and protective effect in reducing oxidative stress and damage in immune cells, especially under inflammatory conditions.