Glutathione Peroxidase Activity Levels Research Articles

Assessing the possible association between MTHFR (rs1801133) and GPx-1 (rs1050450) polymorphisms with the risk of type 2 diabetes, diabetic neuropathy, and diabetic retinopathy.

Oxidative stress in chronic hyperglycemia could injure the tissues and onset of diabetes-related complications like retinopathy and neuropathy. This study investigates the association between methylenetetrahydrofolate reductase (MTHFR) and glutathione peroxidase (GPx) genetic variants with these complications. In this case-control study, 400 individuals, including 100 healthy subjects and 300 patients with type 2 diabetes mellitus (T2DM) in three subgroups: with retinopathy(n = 100), with neuropathy(n = 100), and without complication (n = 100) from West Iran, were studied. MTHFR (rs1801133) and GPx-1 (rs1050450) variants were identified by the PCR-RFLP method. The plasma levels of GPx activity, glutathione, malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative stress (TOS) were measured by chemical methods. Higher BMI, TOS and MDA levels were observed in patients with neuropathy compared to other patients and controls. Diabetic patients with neuropathy had lower levels of glutathione (7.8 ± 4.5; P < 0.001), GPx activity (39.5 ± 8.5; P < 0.001), and TAC (703.1 ± 129.1; P = 0.0001) in comparison with other groups. The patients without complication and retinopathic patients had higher plasma levels of glutathione (12.2 ± 2.4; p = 0.02) and TAC (793.4 ± 124.6; P < 0.001), respectively. MTHFR TT genotype significantly correlated with lower levels of TOS (3.5 ± 1.1; P < 0.001) and OSI (0.0050 ± 0.001; P < 0.001). Subjects with the GPx-1 TT genotype had higher levels of MDA (6.8 ± 2.5; P = 0.02) and lower levels of TOS (3.7 ± 1.6; P < 0.001), which is statistically significant. TT genotype of MTHFR was associated with 3.9 fold (95% CI 1.04-4.76; P = 0.0436) increased risk of neuropathy. Also, GPx-1 CT genotype increased the risk of retinopathy [OR = 2.7 (95% CI = 1.38-5.44; P = 0.0039)]. The MTHFR TT genotype increased the risk of neuropathy in diabetic patients significantly. The GPx-1 CT genotype is related to increased retinopathy risk among diabetic patients. Both MTHFR and Gpx-1 TT genotypes were associated with higher BMI levels.

Copper toxicity in juvenile largemouth bass (Micropterus salmoides): acute toxicity bioassay and oxidative stress response in gut and kidney

Aquaculture intensification has resulted in serious disease outbreaks in largemouth bass production. Compounds containing copper (Cu) are widely used as therapeutic agents in aquaculture. Currently, Cu misuse has been a severe issue in largemouth bass farming. However, few investigations have been performed on Cu toxicity in largemouth bass so far. In this study, an acute and a chronic toxicity test was carried out to determine the toxicity and the recommended dose of waterborne Cu in largemouth bass. In the acute toxicity bioassay, fish (2.58 ± 0.03 g) were exposed to 0 (control), 3, 6, 9, 18, or 30 mg/L Cu, and the results showed that the 96-h LC50 of waterborne Cu was 12.78 mg/L. Then a 30-day chronic toxicity test containing six treatments (i.e., 0, 51.3, 164, 513, 1640, and 5130 μg/L Cu) was conducted to investigate the influence of Cu on intestinal and renal health in terms of oxidative stress in juvenile largemouth bass (2.69 ± 0.02 g). The results showed that Cu concentrations at and above 51.3 μg/L significantly increased the malondialdehyde contents (in the intestine) and simultaneously decreased total superoxide dismutase activity levels (in the intestine and kidney), glutathione peroxidase activity levels (in the kidney), and reduced glutathione contents (in the kidney), compared to control. In contrast to control, fish exposed to high Cu concentrations (at and above 1640 μg/L) demonstrated lower catalase activity levels in the intestine and kidney. Based on the findings in the study, waterborne Cu content for largemouth bass farming was recommended to be less than 51.3 μg/L.

Exploring the Associations of Inflammatory and Oxidative Stress Biomarkers with Pancreatic Diseases: An Observational and Mendelian Randomisation Study.

Identifying biomarkers linked to pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) is crucial for early detection, treatment, and prevention. Methods: Association analyses of 10 serological biomarkers involved in cell signalling (IFN-γ, IL-6, IL-8, IL-10), oxidative stress (superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities, total glutathione (GSH), malondialdehyde (MDA) levels), and intestinal permeability proteins (zonulin, I-FABP2) were conducted across PDAC (n = 12), CP (n = 21) and control subjects (n = 23). A Mendelian randomisation (MR) approach was used to assess causality of the identified significant associations in two large genetic cohorts (FinnGen and UK Biobank). Results: Observational results showed a downregulation of SOD and GPx antioxidant enzyme activities in PDAC and CP patients, respectively, and higher MDA levels in CP patients. Logistic regression models revealed significant associations between CP and SOD activity (OR = 0.21, 95% CI [0.05, 0.89], per SD), GPx activity (OR = 0.28, 95% CI [0.10, 0.79], per SD), and MDA levels (OR = 2.05, 95% CI [1.36, 3.08], per SD). MR analyses, however, did not support causality. Conclusions: These findings would not support oxidative stress-related biomarkers as potential targets for pancreatic diseases prevention. Yet, further research is encouraged to assess their viability as non-invasive tools for early diagnosis, particularly in pre-diagnostic CP populations.

Obesity-dependent molecular alterations in fatal COVID-19: A retrospective postmortem study of metabolomic profile of adipose tissue.

We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI],26.5 ± 2.3 kg m-2) or obese (OBBMI 34.2 ± 5.1 kg m-2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OBgroup showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.

GSH-related enzyme activity and tumor relation: glutathione peroxidase and glutathione reductase status under hypoxia in HepG2 cells

Abstract Objectives In hepatocellular carcinoma (HCC), tumorigenesis, hypoxia and reactive oxygen species (ROS) play a crucial role in altering the tumor microenvironment (TME). Until now, the time-dependent alteration of hypoxia-inducible factor-1α (HIF-1α), the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR) under hypoxic conditions in HCC were not clear. Consequently, our main target was to investigate the role of GPx and GR status in HCC cell line (HepG2) under hypoxic conditions. Methods HIF-1α protein levels in cell lysates were determined by ELISA assay and protein expressions were identified using western blot. GPx and GR activity levels of the cell lysates were measured spectrophotometrically. Results HIF-1α protein levels were determined under normoxic and hypoxic conditions (p&lt;0.001). Also, HIF-1α protein levels and expressions were observed under time-dependent hypoxic conditions, the HIF-1α protein level is found to be reached its peak point at 4 h in the HepG2 cell line. We also have detected decreased activity levels of GPx and increased GR activity levels under hypoxia for 4 h (p&lt;0.001). Conclusions More than 4 h of exposure to hypoxic environment reducted the HIF-1α levels in HCC cells. According to the results, we suggest the ideal exposure time to hypoxic conditions as 4 h for the HepG2 cell line. In addition, hypoxia also stimulated the activity levels of GPx and GR. Our results suggest that the activity levels of GPx and/or GR enzymes may be therapeutic targets in the hypoxia-dependent HCC tumorigenesis process.

Efficacy of nutritional selenium nanoparticles on growth performance, immune response, antioxidant capacity, expression of growth and immune-related genes, and post-stress recovery in juvenile Sobaity seabream (Sparidentex hasta)

This study evaluated the impacts of nano-Se on the growth, immunity, antioxidant capacity, physiological parameters, gene expression, and stress resistance of fingerling Sobaity seabream (Sparidentex hasta). The fish with an average weight of 21.5 ± 0.1 g were divided into four treatment groups in triplicates that received one of the test diets supplemented with varying levels of nano-Se: 0 (control), 0.5 (Se-0.5), 1 (Se-1), and 2 (Se-2) mg/Kg for 60 days. The results showed that final weight, weight gain rate, specific growth rate, feed intake, and feed conversion ratio improved with significant linear and quadratic trends (P < 0.05) in response to nano-Se-supplemented diets, and the best values were measured in the Se-2 group. Superoxide dismutase activity level remained unaffected among the four groups (P > 0.05). Catalase activity increased in nano-Se-supplemented groups, with the highest level measured in fish fed the Se-0.5 diet. Glutathione peroxidase activity levels were not significantly different between the control and nano-Se groups, but the lowest malondialdehyde concentration was detected in the Se-2 group. Nano-Se had no marked effect on total plasma Ig levels; however, the highest lysozyme activity and alternative complement activity (ACH50) were observed in the Se-0.5 and Se-2 groups, respectively. No significant differences (P > 0.05) were observed in plasma total protein, albumin, globulin, triglyceride, and thyroid hormone (T3 and T4) contents among the groups. However, the lowest cholesterol and low-density lipoprotein values and the highest high-density lipoprotein concentration were measured in the Se-2 group. The Se-0.5 and Se-1 groups exhibited significantly lower levels of aspartate aminotransferase activity, and the lowest alkaline phosphatase activity level was detected in the Se-1 group. The expression level of insulin-like growth factor I gene in all nano-Se-fed groups was significantly higher than the control. Also, the expression of interleukin-1β and lysozyme genes was significantly upregulated in nano-Se-supplemented groups, with the highest values in the Se-2 group. Following acute crowding stress, plasma cortisol and lactate levels at all post-stress time intervals were not significantly different among the experimental groups. Fish fed the Se-0.5 and Se-2 diets tended to have lower plasma glucose concentrations than other groups. In conclusion, dietary nano-Se at 2 mg/kg is recommended to promote growth performance and enhance antioxidant and immune parameters in Sobaity juveniles.

Neuroprotective effects of rosemary extract on white matter of prefrontal cortex in old rats.

During aging, cerebral structures undergo changes due to oxidative stress. The consumption of some plants seems to improve neurological health. For example, rosemary extract (RE) which is widely used as a flavoring food has anti-inflammatory and anti-oxidant activities. Therefore, we aimed to study the effect of RE on the changes related to the aging process in the prefrontal cortex (PFC). Twenty-four male Wistar rats including young and old were purchased. Each group was divided into two subgroups: vehicle and rosemary (old vehicle (OV), old rosemary (OR), young vehicle (YV), and young rosemary (YR) groups). Then, we examined the number of intact neurons, myelin base protein (MBP), white matter (WM), levels of malondialdehyde (MDA), and glutathione peroxidase (GPx) in the PFC. The results showed that in the old vehicle rats compared to the young group without treatment, except for the MDA level (which increased), other variables significantly decreased (P≤0.05). Additionally, RE consumption demonstrated a significant elevation of WMA, MBP intensity, number of intact neurons, and GPx activity level, while MDA levels significantly reduced in the treated old rats compared to the old vehicle group (P≤0.05). However, there was no significant difference between the OR and YV groups (P≥0.05). Overall, it seems that RE can protect and improve aging damages in the PFC due to its anti-oxidant properties. So, the use of RE can be a suitable strategy to prevent aging complications in the brain.

Use of hydrobalneotherapy in ambulatory rehabilitation of patients with post-COVID syndrome

BACKGROUND: Post-COVID syndrome ostcoid syndrome is a consequence of the multimodal systemic effect of the SARS-CoV-2 virus on the human body, and leads to a variety of clinical symptoms that require correction. In particular, there is an increase in the level of allostatic load and the risk of maladaptation. One of the means of effective non-drug effects on the separated consequences of COVID-19 is the use of hydrobalneotherapy methods as part of a rehabilitation course.&#x0D; AIM: To study the influence of various hydrobalneotherapy methods as part of comprehensive outpatient rehabilitation on the clinical-functional and psychoemotional status of patients with post-COVID syndrome.&#x0D; MATERIALS AND METHODS: 160 patients undergoing outpatient rehabilitation for manifestations of post-COVID syndrome, 74 men and 86 women, with a median age of 50 [43; 55.1] years, were comprehensively examined. Patients were randomized to 4 groups of 40, depending on the non-drug exposure method in the rehabilitation program: 1st group ― with the inclusion in the individual rehabilitation program of a course of chloride-sodium mineral baths in the amount of 10 procedures, 2nd group ― patients who were assigned a 10-day course of hot tubs, 3rd group ― 40 patients, along with exercise therapy, who underwent a 10-day course of general baths "Biolong", and 4th, control group of patients who did not undergo outpatient rehabilitation.&#x0D; RESULTS: The most frequent complaints were increased fatigue ― 88.8% of subjects, memory loss ― 46.9%, headache and dizziness ― 38.8%, dyspnea during physical activity ― 35.6%. The most frequent electrocardiogram parameters were sinus tachycardia (4.4%) and sinus bradycardia (8.1%). The mean allostatic load index of all patients was 3 [2; 3], which corresponds to the average allostatic overload. Against the background of rehabilitation measures with the inclusion of preformed physical factors, regression of the main complaints (weakness was detected in 24.2% of cases, memory decline ― in 20%, headache, dizziness ― in 17.5%, dyspnea ― in 15%, sleep disturbance ― in 10%, tachycardia and discomfort in the heart area ― in 7.5%) and improvement of electrocardiogram parameters were noted: sinus tachycardia and ventricular extrasystole were not noted, bradycardia was recorded in 2.5% of cases instead of 8.1%, repolarization process disorders ― in 2.5% instead of 8.1% before rehabilitation. In the group of patients who received whirlpool baths, improvement of external respiratory function parameters was noted: forced vital capacity of lungs increased by 12.1% (p 0.01), forced expiratory volume in the 1st second ― by 9.6% (р 0.05), the distance traveled according to the results of the test with 6-minute walking increased by 2.2% (р 0.05). In the group of those who received general baths with the preparation "Biolong", there was registered an increase in forced expiratory volume in the 1st second by 9.4% (р 0.05), an increase in the distance traveled during the 6-minute walk test by 8, 3% (р 0.05), decrease in norepinephrine level by 17.4% (р 0.05), adrenaline level by 13% (р 0.05) and cortisol level by 26.2% (р 0.01), glutathione peroxidase activity level by 13.6% (р 0.05). In the group of patients who received sodium chloride baths, there was a tendency to improvement of central hemodynamic parameters, reduction of adrenaline and noradrenaline parameters by 14.5% and 19.7% respectively (р 0.05). All rehabilitation groups showed a decrease in the Beck depression scale and Spielberger anxiety scale, K. Maslach questionnaire (emotional exhaustion and reduction of personal achievements), Bass–Perry aggression level questionnaire and Schulte table (mental stability), as well as a decrease in the level of allostatic load. In the control group, no dynamics of complaints and indicators was noted.&#x0D; CONCLUSION: In patients with post-COVID syndrome, a variety of complaints and a number of electrocardiogram disorders, clinical and functional parameters were identified. The study revealed positive dynamics against the background of the rehabilitation course with the inclusion of hydrobalneotherapy methods in the form of significant regression of complaints, clinical and functional disorders and changes in psychoemotional background and cognitive status. A decrease in allostatic load was noted after a course of non-drug rehabilitation.

Oxidative stress induction by OCPs and OPPs pesticides may cause lung cancer incidence

Background and aims Pesticides are nowadays known as one of the most important causes of human disorders worldwide. The aim of the present study was to investigate the role of organochlorine pesticides (OCPs) and organophosphorus pesticides (OPPs) in the development of lung cancer. Methods We determined the levels of seven derived OCP residues (α-HCH, β-HCH, γ-HCH, 2,4 DDT, 4,4 DDT, 2,4 DDE, and 4,4 DDE) and enzymatic antioxidant biomarkers including paraoxonase-1 (PON-1), erythrocyte’s acetylcholinesterase (AChE), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and non-enzymatic antioxidant biomarkers, including total antioxidant capacity (TAC), protein carbonyl (PC), malondialdehyde (MDA), and nitric oxide (NO) in the blood samples of 51 lung cancer patients and 51 healthy subjects as controls. Furthermore, the effects of OPP exposure on the development of lung cancer and oxidative stress (OS) are indirectly assessed by measuring AChE and PON-1 enzyme activities. Results The average values of all the measured OCPs were significantly higher in lung cancer patients when compared with healthy control subjects (p < 0.05). AChE, PON-1, GPx, and CAT activity levels, as well as the amounts of PC, MDA, and NO were higher in patients with lung cancer than in the control subjects (p < 0.05), while TAC values were lower in the patients. Moreover, our data showed a significant association between OCP concentrations and OS parameters (p < 0.05). Conclusion The results suggest that OCPs and OPPs may have a role in lung cancer incidence in southeastern Iran, and at least one of the mechanisms by which OCPs and OPPs may contribute to increasing the development of lung cancer in the studied area is through OS generation.

Assessment of antioxidant system status before and after operation in neonates with congenital heart disease.

Oxidative stress is considered to have a significant role in the development of cardiovascular diseases (CVDs) as well as many other diseases. Therefore, the purpose of the study is to evaluate the antioxidant system status at pre- and post-operative period in newborns with congenital heart disease (CHD) requiring operation. Fifty CHD patients participated in this research. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and thiobarbituric acid reactive substances (TBARS) levels were studied in blood samples. RACHS-1 score, blood lactate levels, and hypoxic events were also recorded. Comparisons of antioxidant system parameters were conducted at pre- and post-operative periods and also between exitus and discharged groups. GPx activity and TBARS levels were significantly higher in the pre-operative period than post-operative period though the other antioxidant enzymes were not altered. In pre-operative period, GPx activity was low in addition to rarer hypoxic events in the discharged group. Also, a negative correlation was found between SOD and GPx activities in pre-operative period. The results provide fundamental data showing the lowered GPx activity and TBARS levels considered as sensitive oxidative biomarkers after the operation. It was assumed that antioxidant system parameters might show changes after the operation, and GPx is prominent for resistance to hypoxic conditions. Post-operative reduction of GPx and TBARS levels is significant for evaluating the antioxidant system alterations after the operation. However, further investigations follow long-term duration for post-operative monitoring to estimate how antioxidant system status changes to improve the treatment of the health condition.

Effect of Eight Weeks of Resistance Training on Inflammatory Markers and Antioxidant Indices of Kidney Tissue Following Testosterone Enanthate Abuse in Male Rats

Introduction: Abuse of anabolic steroids can lead to kidney tissue damage.The aim of this study was to investigate the effect of eight weeks of resistance training on inflammatory markers and antioxidant indices of kidney tissue of male rats following testosterone enanthate abuse.&#x0D; Methods: In this experimental study, 24 male Wistar rats were randomly divided into three groups: 1) Control, 2) Training and 3) Training + Testosterone. Rats in groups 2 and 3 performed resistance training five sessions a week for eight weeks. Moreover, group 3 received 20 mg/kg of testosterone enanthate intramuscularly three days a week. The activity levels of Superoxide dismutase (SOD) and Glutathione peroxidase (GPx) were measured by spectrophotometric method and the gene expression of Interleukin-6 (IL-6) and Tumor necrosis factor alpha (TNF-α) were measured by Real Time PCR method. The data were analyzed using SPSS version 16 software. To analyze the findings, To analyze the findings, one-way analysis of variance was used (P≥0.05).&#x0D; Results: Resistance training caused a significant decrease in GPx activity (P=0.001) compared to the control group. IL-6 gene expression in the training + testosterone group was significantly more than the training group (P=0.04) and the control group (P=0.001). Training + testosterone caused a significant increase in TNF-α gene expression compared to the training group (P=0.02) and the control group (P=0.008). Furthermore, the level of GPx activity in the training + testosterone group was significantly lower than the control group (P=0.001), but no significant difference was observed in the training + testosterone groups and the training group (P=0.93).&#x0D; Conclusion: It seems that testosterone abuse along with intense resistance training is associated with a decrease in the function of the antioxidant system and increase in inflammatory markers in the kidney tissue.

Gastroprotective effects of bromelain on indomethacin-induced gastric ulcer in rats

Gastric ulcer is one of the most common diseases of the gastrointestinal system and some of its complications are the main causes of morbidity and mortality. Bromelain (BRM), a sulfhydryl proteolytic enzyme, has multiple activities in many areas of medicine as an antioxidant and anti-inflammatory agent. In this study, it was aimed to investigate the anti-inflammatory and oxidative stress-mediated therapeutic effect of BRM in a gastric ulcer model induced by indomethacin (IND) which is a non-steroidal anti-inflammatory drug (NSAID) with gastric ulcer-forming effects. Gastric mucosal paraoxonase (PON), arylesterase (ARE), catalase (CAT), myeloperoxidase (MPO) and glutathione peroxidase (GPx) activity and total glutathione (GSH) levels were analyzed. Interleukin-33 (IL-33), the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) levels were determined by immunohistochemically. Although IND-induced histopathological changes occurred, BRM pretreatment prevented these effects. As a result of the study, it was determined that BRM had an anti-ulcerative effect at a dose of 50 mg/kg. BRM given at this dose significantly decreased gastric tissue MPO activity, and increased CAT, PON, ARE, GPx activity and GSH level. The increased IL-33 and decreased Nrf-2 and HO-1 levels were obtained in IND group and these changes were reversed by BRM. As a result, it was concluded that BRM may have protective effects in IND-induced gastric model by reducing inflammation and regulating oxidant/antioxidant balance.

Comparative Analysis of the Pre- and Post-Medication Effects of Antipsychotic Agents on the Blood-Based Oxidative Stress Biomarkers in Patients with Schizophrenia: A Meta-Analysis.

Studies have shown that oxidative stress (OS) is related to the pathophysiology of schizophrenia (SCZ), but whether antipsychotics can induce OS has not been investigated well. Moreover, antipsychotics have differential effects on the OS level modulation, i.e., different types of antipsychotics have different effects on the cellular antioxidants or pro-oxidants. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and investigated the OS indicators including both enzymatic and nonenzymatic markers, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), glutathione (GSH), vitamin C, etc., of SCZ patients at baseline and follow-up of mono-medication. Twenty studies met the inclusion criteria, with a total of 1162 patients enrolled at baseline, and 1105 patients completed the follow-up. OS markers were changed after a period of antipsychotic treatment in SCZ patients. The GPx activity and MDA level decreased in the whole blood (P<0.05), also the serum MDA level decreased (P<0.05). For the first-episode SCZ patients, the activity of GPx and the level of MDA decreased, while the level of vitamin C increased (all P<0.05). The levels of MDA in patients receiving atypical antipsychotics decreased (P<0.05), while the level of GSH in patients with typical antipsychotics decreased (P=0.05). Antipsychotic medication may cause changes in the levels of OS markers in different blood samples of SCZ patients. However, the available studies might not be sufficient to reveal the underlying facts accurately due to the poor quality of experimental designs in the published literature.

Uticaj vitamina B6 na markere oksidativnog stresa, kardiometaboličke i histološke markere u uslovima monokrotalinom indukovane srčane slabosti kod Wistar albino pacova

Introduction/Aim: Heart failure (HF) induced by monocrotaline (MCT) is common in the pulmonary arterial vessels remodeling mechanisms with increased pulmonary resistance and oxidative stress markers. The purpose of this study was to validate the hypothesis that the treatment with vitamin B6 could affect HF by modulating cardiometabolic and oxidative stress biomarkers, and the structure of the rat heart. Material and Methods: Male Wistar albino rats were divided into 3 groups: blank solution-exposed control (C physiological saline 1ml/kg 28 days ip., n=8), B6 (vitamin B6 7mg/kg/day 28 days ip., n=8), and MCT+B6 (MCT 50mg/ kg once ip. plus vitamin B6 7mg/kg/day 28 days ip., n=8). Results: The four-week vitamin B6 treatment significantly affected certain biochemical parameters. The activity of key antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPX) did not change, whereas the total glutathione (GSH) was significantly decreased in the MCT+B6 group. This was followed by a slightly decreased level of the total glutathionylation observed in the MCT+B6 group. The parameters of protein oxidative damage (reactive carbonyl derivates, thiol groups and nitrotyrosine) did not significantly change in the MCT+B6 group. An increasing trend in RV and LV wall thickness was observed in the MCT+B6 compared to the C group, as well as in Ki67 and PCNA positivity. Conclusion: The four-week treatment with vitamin B6 significantly affected certain biomarkers. The activity of SOD and nitrotyrosine content did not change, while GPX activity, total glutathione and total glutathionylation level were decreased in the MCT+B6 group. We observed an increase in RV and LV wall thickness in the MCT+B6 group compared to the C group, as well as in Ki67 and PCNA positivity.

Melatonin and MitoEbselen-2 Are Radioprotective Agents to Mitochondria.

Mitochondria are responsible for controlling cell death during the early stages of radiation exposure, but their perturbations are associated with late effects of radiation-related carcinogenesis. Therefore, it is important to protect mitochondria to mitigate the harmful effects of radiation throughout life. The glutathione peroxidase (GPx) enzyme is essential for the maintenance of mitochondrial-derived reactive oxygen species (ROS) levels. However, radiation inactivates the GPx, resulting in metabolic oxidative stress and prolonged cell injury in irradiated normal human fibroblasts. Here, we used the GPx activator N-acetyl-5-methoxy-tryptamine (melatonin) and a mitochondria-targeted mimic of GPx MitoEbselen-2 to stimulate the GPx. A commercial GPx activity assay kit was used to measure the GPx activity. ROS levels were determined by using some ROS indicators. Protein expression associated with the response of mitochondria to radiation was assessed using immunostaining. Concurrent pre-administration or post-administration of melatonin or MitoEbselen-2 with radiation maintained GPx activity and ROS levels and suppressed mitochondrial radiation responses associated with cellular damage and radiation-related carcinogenesis. In conclusion, melatonin and MitoEbselen-2 prevented radiation-induced mitochondrial injury and metabolic oxidative stress by targeting mitochondria. These drugs have the potential to protect against acute radiation injury and late effects of carcinogenesis in a variety of radiation scenarios assuming pre-administration or post-administration.

Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development.

Decreased selenium (Se) levels during childhood and infancy are associated with worse respiratory health. Se is biologically active after incorporation into Se-containing antioxidant enzymes (AOE) and proteins. It is unknown how decreased maternal Se during pregnancy and lactation impacts neonatal pulmonary selenoproteins, growth, and lung development. Using a model of neonatal Se deficiency that limits Se intake to the dam during pregnancy and lactation, we evaluated which neonatal pulmonary selenoproteins are decreased in both the saccular (postnatal day 0, P0) and early alveolar (postnatal day 7, P7) stages of lung development. We found that Se deficient (SeD) pups weigh less and exhibit impaired alveolar development compared to Se sufficient (SeS) pups at P7. The activity levels of glutathione peroxidase (GPx) and thioredoxin reductase (Txnrd) were decreased at P0 and P7 in SeD lungs compared to SeS lungs. Protein content of GPx1, GPx3 and Txnrd1 were decreased in SeD lungs at P0 and P7, whereas Txnrd2 content was unaltered compared to SeS controls. The expression of NRF-2 dependent genes and several non-Se containing AOE were similar between SeS and SeD lungs. SeD lungs exhibited a decrease in selenoprotein N, an endoplasmic reticulum protein implicated in alveolar development, at both time points. We conclude that exposure to Se deficiency during pregnancy and lactation impairs weight gain and lung growth in offspring. Our data identify multiple selenoproteins in the neonatal lung that are vulnerable to decreased Se intake, which may impact oxidative stress and cell signaling under physiologic conditions as well as after oxidative stressors.

Selenium: a potent regulator of ferroptosis and biomass production

Emerging evidence supports the notion that selenium (Se) plays a beneficial role in plant development for modern crop production and is considered an essential micronutrient and the predominant source of plants. However, the essential role of selenium in plant metabolism remains unclear. When used in moderate concentrations, selenium promotes plant physiological processes such as enhancing plant growth, increasing antioxidant capacity, reducing reactive oxygen species and lipid peroxidation and offering stress resistance by preventing ferroptosis cell death. Ferroptosis, a recently discovered mechanism of regulated cell death (RCD) with unique features such as iron-dependant accumulation of lipid peroxides, is distinctly different from other known forms of cell death. Glutathione peroxidase (GPX) activity plays a significant role in scavenging the toxic by-products of lipid peroxidation in plants. A low level of GPX activity in plants causes high oxidative stress, which leads to ferroptosis. An integrated view of ferroptosis and selenium in plants and the selenium-mediated nanofertilizers (SeNPs) have been discussed in more recent studies. For instance, selenium supplementation enhanced GPX4 expression and increased TFH cell (Follicular helper T) numbers and the gene transcriptional program, which prevent lipid peroxidase and protect cells from ferroptosis. However, though ferroptosis in plants is similar to that in animals, only few studies have focused on plant-specific ferroptosis; the research on ferroptosis in plants is still in its infancy. Understanding the implication of selenium with relevance to ferroptosis is indispensable for plant bioresource technology. In this review, we hypothesize that blocking ferroptosis cell death improves plant immunity and protects plants from abiotic and biotic stresses. We also examine how SeNPs can be the basis for emerging unconventional and advanced technologies for algae/bamboo biomass production. For instance, algae treated with SeNPs accumulate high lipid profile in algal cells that could thence be used for biodiesel production. We also suggest that further studies in the field of SeNPs are essential for the successful application of this technology for the large-scale production of plant biomass.

Effect of vitamin B3 supplementation on glutathione redox cycle

In this study, the effect of vitamin B3 supplement given to rats was investigated on glutathione redox cycle by looking at glutathione peroxidase and glutathione s transferase activities. 20 Wistar albino male rats were used. Vitamin B3 supplement was given to one of the two groups that were formed. The other group was determined as the control group. 360 mg/kg/day vitamin B3 supplement was given by oral gavage method for 10 days. At the end of 10 days, intracardiac blood samples were taken. Glutathione peroxidase activity level was determined as 1033.44±198.05 U/L in the vitamin B3 supplement group and 526.00±99.54 U/L in the control group. The glutathione peroxidase activity level of the vitamin B3 supplemented group was found to be statistically significantly higher than the glutathione peroxidase activity level of the control group (p

Cardioprotective effect of Justicia gendarussa on doxorubicin induced toxicity in mice.

Justicia gendarussa Burm.f, belonging to the family Acanthaceae, is widely used for various ailments traditionally. Antioxidant, anti-arthritic, anti-inflammatory, analgesic, anticancerous, properties of the plant have been widely reported. The present study analyzed the cardioprotective effect of J.gendarussa on doxorubicin (DOX) induced toxicity in mice. Ethanolic extract of J.gendarussa was administered orally for 7 consecutive days. The alterations in oxido-reduction status, biochemical and histopathological parameters were analyzed in heart tissue. DOX increased superoxide dismutase (SOD) and catalase activities to 3.4±0.5 and 3.68±1 from their normal values 2.43±0.8 and 2.72±0.88, respectively. The increased activities of both the enzymes were found reduced to 3.12±0.24 and 3.41±0.65 by the treatment of the extract. Similarly, DOX elevated glutathione peroxidase (GPx) activity to 44.6±3.71 from the normal level 32.33±3.41. DOX decreased the glutathione (GSH) level to 15.66±2.51 from the normal values 31.66±4.05. Upon treatment, GPx activity and GHS level found restored. The increased lipid peroxidation 2.53±0.25 of DOX was also decreased to 2.0±0.34 by the extract. Histopathology observations substantiate the protective effect of J.gendarussa extract. In conclusion, DOX-induced disturbance of oxido-reduction status and histopathology of heart attenuated closer to the normal indicating the protective effect of J.gendarussa against DOX-induced toxicity in cardiomyocytes.

Metabolomic profiling and alleviation of oxidative stress of Huangjing Zanyu capsule treating oligoasthenospermia.

BackgroundThe traditional Chinese medicine (TCM) patent medicine Huangjing Zanyu capsule (HJZY capsule) has achieved satisfactory clinical effects in the treatment of oligoasthenospermia (OAS). This study aimed to elucidate the impact of HJZY capsule on the reproductive system, focusing on oxidative stress and metabolism profiling during the intervention, to clarify the therapeutic mechanism of HJZY capsule in treating OAS.MethodsCyclophosphamide was used to establish OAS model rats. Time-sequence specimen collection was applied to monitor the dynamic development of the pharmacological effect of HJZY capsule. Superoxide dismutase (SOD), glutathione peroxidase (GPX), and malonaldehyde (MDA) were evaluated by biochemistry kits to examine the impact of HJZY capsule on oxidative stress. Non-targeted metabolomics was conducted for urine and testis samples, respectively, to investigate metabolic pathways through which the HJZY capsule takes effect.ResultsThe HJZY capsule elevated sperm density from 62.1±8.28, passing 68.4±7.52, to 75.9±8.48×106/mL, and sperm motility from 62.0%±3.94%, passing 70.8%±9.72%, to 68.8%±4.37%. Meanwhile, SOD (P<0.05 in week 2) and GPX activity levels of HJZY groups were elevated to a certain degree, respectively, and lipid oxidation was attenuated, as shown by decreased MDA content (P<0.05 in week 2). Metabolomics results showed that the HJZY capsule could modulate pathways including taurine metabolism, purine and pyrimidine metabolism, glycerolipid and glycerophospholipid metabolism, and multiple amino acid metabolisms, among others. The cluster analysis results showed that urinary and testicular metabolomics differed in the strength of discrimination between rats in the OAS model and the HJZY groups.ConclusionsThe HJZY capsule exerts a comprehensive effect on OAS through influencing various metabolic pathways. Non-targeted metabolomics provides an effective way for profiling complex TCM prescriptions.