Glutathione Peroxidase Activity Research Articles

The Protective Effects and Mechanism of Mulberry Leaf Flavonoids on Type 2 Diabetic Nephropathy Mice

Purpose: This study investigated the protective effects and mechanism of mulberry leaf flavonoids on type 2 diabetic nephropathy (DN) in mice. Methods: The DPPH free radical scavenging activity of mulberry leaf flavonoids was measured in vitro. To establish a type 2 DN model, male ICR mice were induced with streptozotocin (STZ) after a high-fat diet regimen. The mice were then divided into groups: a normal control group, a DN model group (DM), a positive control group receiving 200 mg/kg metformin (Met group), and a treatment group receiving 1 g/kg mulberry leaf flavonoids (FM group). Both Met and FM groups received daily intragastric administration for 4 weeks, while the DM and control groups were given equivalent volumes of normal saline. Fasting blood glucose levels were recorded regularly during the intervention. After the treatment period, serum creatinine (CRE), blood urea nitrogen (BUN), superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, and renal glutathione peroxidase (GPx) activity were measured. Additionally, kidney histopathological changes and glycogen deposition were evaluated by HE and PAS staining, while Nrf2 and HO-1 expression in kidney tissue was assessed through immunohistochemistry. Results: Mulberry leaf flavonoids effectively scavenged free radicals, significantly reduced blood glucose levels, CRE, BUN, and MDA in serum and kidney tissues, and increased SOD and GPx activities. Histopathological improvements in kidney and pancreatic tissues were observed, alongside increased Nrf2 and HO-1 expression. Conclusions: Mulberry leaf flavonoids ameliorate renal damage in DN mice, potentially through oxidative stress reduction and activation of the Nrf2/HO-1 signaling pathway.

DEHP impairs the oxidative stress response and disrupts trace element and mineral metabolism within the mitochondria of detoxification organs.

Di(2-ethylhexyl) phthalate (DEHP), a widely utilized plasticizer in various consumer products, is classified as an endocrine disruptor and has been implicated in numerous adverse health effects, including oxidative stress, inflammation, and metabolic disturbances. Despite the growing body of literature addressing the systemic effects of DEHP, the specific influence of DEHP-induced oxidative stress on mitochondrial function within detoxification organs, particularly the liver and kidneys, remains largely unexplored. This study evaluated the effects of DEHP exposure (0, 100, 200, and 400mg/kg/day) on mitochondrial oxidative stress, trace elements, and mineral metabolism associated with signaling pathways in the liver and kidneys of rats. Altered mitochondrial oxidative stress status was indicated by impaired glucose 6-phosphate dehydrogenase (G6PD), 6-phosphoglucerate dehydrogenase (6-PGD), glutathione reductase (GR), glutathione s-transferase (GST), and glutathione peroxidase (GPx) activities, along with significant disruptions in essential minerals and trace elements, including Na, Mg, Cu, Zn, and Fe. Key oxidative stress signaling pathways, such as NF-κB, Akt, STAT3, and CREB, glucose, and tissue homeostasis, displayed dose-dependent responses to DEHP, indicating complex regulatory mechanisms. This study represents the first comprehensive investigation into DEHP-induced mitochondrial dysfunction, highlighting its effects on oxidative stress metabolism, trace element homeostasis, and cellular signaling pathways in detoxification organs. These findings provide novel insights into the mitochondrial mechanisms underlying DEHP toxicity and underscores the need for further research into the implications of plasticizer exposure on human health.

Oxidative stress and apoptosis of the spinal cord in a rat model of retinoic acid-induced neural tube defects.

Neural tube defects (NTDs) are severe congenital anomalies that significantly impact the central nervous system, arising from the neural tube's failure to close during early embryogenesis. In this study, we investigated NTDs and associated pathophysiological mechanisms in foetal rats following exposure to all-trans retinoic acid (atRA). Out of 168 embryos from 15 pregnant rats in the experimental group, 78% displayed NTDs with notable spinal deformities, primarily in the lumbar-sacral region, similar to human cases. Body weight and crown-rump length (CRL) measurements indicated significant growth impairment in the NTD group compared to controls, while the atRA-treated group without NTDs showed no notable differences in growth. Immunohistochemistry (IHC) results demonstrated decreased NeuN and PCNA expression in the NTD group's spinal cord. Oxidative stress markers showed markedly reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity, alongside increased malondialdehyde (MDA) levels in the NTD group, indicating heightened oxidative stress. Analysis of apoptosis-related proteins revealed elevated Bax and caspase-3 levels, reduced Bcl-2 and lower poly (ADP-ribose) polymerase (PARP) in the NTD group, suggesting a pronounced shift towards proapoptotic pathways, potentially contributing to NTD progression. Our findings indicate that oxidative stress and apoptosis play significant roles in the development of NTDs. Future investigations should aim to pinpoint critical regulatory genes or proteins that might be targeted for therapeutic interventions to alleviate oxidative stress and apoptosis in NTD development.

Combined extracts of Syzygium aromaticum (Clove) and Xylopia aethiopica (Negro pepper) seeds inhibit testosterone propionate-induced benign prostatic hyperplasia in Wistar rats

Objective: Study aimed to determine the inhibition of benign prostate hyperplasia (BPH) in rats using combined extracts of Syzygium aromaticum and Xylopia aethiopica. Methods: Twenty male Wistar rats were divided into four groups:(i) normal control (NC) received normal saline (0.5 mL); (ii) testosterone propionate (TP); (iii) and (iv)testosterone propionate + 200 and 400 mg/kg b.wt of the extract. Injection was performed subcutaneously, followed by daily oral administration of the extract for 30 days. Results: Prostate weight, testosterone, prostate specific antigen (PSA), and total protein levels increased significantly (p < 0.05) in the TP only compared with those in the NC and decreased in the treatment groups. Cholesterol, TAG, and LDL-chol increased in TP relative to TP-200 and TP-400. HDL increased non-significantly (p > 0.05) across the test groups compared to TP. MDA levels increased significantly (p < 0.05) in the TP compared with those in the test groups. Catalase and glutathione peroxidase (GPx) activities decreased significantly (p < 0.05) in the TP group compared to those in the NC, TP-200, and TP-400 groups. Similarly, superoxide dismutase (SOD) increased inTP-400 compared to that in the TP and NC groups. Decreased PCV %, Hb, RBC and platelets, except WBC, were recorded in TP compared to TP-200 and TP-400. TP-200 and TP-400 presented relatively normal prostatic histomorphology compared with TP. Conclusion: The mechanisms of BPH inhibition involve the regulation of sex hormone levels and the amelioration of conditions caused by oxidative damage. Abbreviations: BPH: benign prostatic hyperplasia; CAT: catalase; DTH: dihydrotestosterone; GPx: glutathione peroxidase; HDL-Chol: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; MDA: malondialdehyde; NC: normal control; PI: prostatic interstitium; PVC: packed cell volume; PSA: prostate specific antigen; SOD: superoxide dismutase; TP: testosterone propionate; TAG: triacylglycerol

Dietary antioxidant capacity is inversely associated with F2- isoprostane and body fat percentage in elite soccer referees

Background Dietary antioxidant Capacity (DaC) has been used as a tool for predicting plasma and dietary antioxidant concentrations. However, the DaC association with oxidative stress (OS) and body composition parameters is an unexplored area, mainly in physically active individuals. Given the potential for increased OS in physically active individuals, it becomes crucial to investigate this association. The aim of this study was to analyze the association between DaC, OS biomarkers, and body composition in healthy and physically active individuals. Methods This Cross-sectional study included 20 male soccer referees. Body composition measurements (body mass, fat mass, lean mass, and waist circumference), OS biomarkers (F2-isoprostane, total antioxidant state, total oxidative status, reduced glutathione, oxidized glutathione, superoxide dismutase, glutathione peroxidase (GPx) and catalase), and DaC were evaluated. Linear regression models were used to determine the association between DaC and the dependent variables. The study was approved by the Human Research Ethics Committee of the Federal University of Santa Catarina (UFSC), CAAE 82584318.0.0000.0121, and file no. 2.572.301. Results DaC was inversely associated with F2-isoprostane (p = 0.044), GPx activity (p = 0.048), and body fat percentage (p = 0.025). Conclusions Increased DaC in physically active individuals may bring benefits related to biomarkers of OS, such as decreasing F2-isoprostane and increasing GPx activity. The increase in DaC also showed an improvement in body composition, demonstrated by the lower percentage of body fat in the study subjects.

EVALUATION OF GLUTATHIONE PEROXIDASE ACTIVITY, MALONYLALDEHYDE AND SELENIUM LEVELS IN SICKLE CELL ANAEMIA INDIVIDUALS ATTENDING NAUTH, NNEWI IN SOUTH-EASTERN NIGERIA.

Background: Oxidative stress is an imbalance between the production and clearance of toxic free radicals known as reactive oxygen species (ROS). It is associated with hemolysis, a hallmark of SCD. SCD has long been recognized as an inflammatory condition and oxidative stress play important role in pathophysiology of SCA. Imbalance between production and elimination of reactive oxygen species (ROS) damages cell structures, including lipids, membranes, proteins and nucleic acids resulting in cell death or altered cell function. Aim: The aim of this study was to measure the serum level of Glutathione peroxidase, Malonaldehyde and Selenium in SCA (HbSS) in their steady state, AA (Healthy adult) and AS (sickle cell carriers) Methods: This is a cross- sectional study. A total of one hundred and fifty aged matched participants were recruited for this study.50 SCA subjects with sickle cell anemia (SS). Glutathione peroxidase and Malonyaldehyde were measured using turbidometry and colorimetric methods respectively while Selenium was analysed using Atomic Absorption Spectrophotometry (AAS) Results: The result of analysis of variance (ANOVA) showed that the mean serum level of MDA concentration (2.97±0.29) was higher in the SS group and was statistically significant (p&lt; 0.05). MDA concentration was lower in the AS group. In the post hoc analysis MDA was statistically significant between SS vs AS and AA vs AA. The glutathione peroxidase activity was significantly lower in the SS group (0.85±0.12) compare with the mean values obtained in the AA and AS group. The GPx activity among the three groups was statistically significant while the post hoc analysis among the three groups showed statistical difference and was significant (p &lt; 0.005) The Selenium levels in the SS group is lower compared with the values observed between the AA and AS group. The Se levels in the SS group was statistically lower (5.73±1.34) (p &lt; 0.05) and showed significant difference. The comparison study between AS vs SS and AA vs AA were statistically significant. Conclusion: The decrease in selenium level potentiates low and weakened antioxidant activity and capacity which also is a reflection of low level of glutathione peroxidase observed which is supposed to attack free radicals to prevent oxidative stress. The findings from this study are in tandem with other researches suggesting that the pathophysiology of sickle cell disease is associated with oxidative stress

Integrated analysis of physiology, antioxidant activity and transcriptomic of Lactobacillus plantarum 120 in response to acid stress

This research examined the effects of acid stress on the physiological and antioxidant activity of Lactobacillus plantarum 120 (Lp-120) and explored its underlying mechanisms. The results revealed that the survival rates of the strain significantly decreased as the pH decreased from 5.5 to 4.5. Meanwhile, the ATP concentrations of the strain decreased from 0.51 to 0.12, and the reactive oxygen species levels rose 1.26-fold with a decrease in pH. However, as the pH decreased, the free radical (DPPH, O2−, and OH−) scavenging activity, reducing power, superoxide dismutase, glutathione peroxidase activities, and the total antioxidant capacities of Lp-120 all increased (P<0.05). Among them, the DPPH scavenging power and superoxide radical scavenging power reached the highest value of 35.5% and 30.74% respectively at pH 4.5, and the hydroxyl radical scavenging power reached the highest value of 53.2% at pH 5.0, which indicated that appropriate acid stress could improve the antioxidant activities of the strain. Transcriptomics data showed that the expression levels of genes (ndh, trxA, etc.) were upregulated (0.39-10.54-fold) under acid stress, which related to the “NADH oxidase/ NADH peroxidase” system, glutaredoxin system and thioredoxin system. Taken altogether, this study brought valuable insights for enhancing the antioxidant activities of Lp-120 and provided valuable information on the application of Lactobacillus plantarum as antioxidant starter cultures in fermented foods.

α -lipoic acid supplementation reduces oxidative stress and inflammation in red skeletal muscle of insulin-resistant rats

α -lipoic acid (ALA) is an eight-carbon saturated fatty acid with strong antioxidant activity. Despite previous reports of ALA's protective properties in treating cardiovascular and metabolic diseases (including insulin resistance and diabetes), little is known about the compound's effects on skeletal muscle metabolism. In particular, the effect of ALA on glycooxidative and nitrosative damage in red muscles during insulin resistance is unknown. This study investigated the therapeutic potential of ALA on the antioxidant barrier as well as oxidative, nitrosative and carbonyl stress in the red skeletal muscle of rats with high-fat diet-induced insulin resistance. Male Wistar cmdb/outbred rats were divided into four equal groups: control diet (CTRL), high fat diet (HFD), CTRL+ALA (30 mg/kg body weight for 4 weeks; intragastrically) and HFD+ALA. Enzymatic and nonenzymatic antioxidant systems, protein and lipid glycoxidation, nitrosative stress, and selected inflammatory/apoptosis parameters were assessed using colorimetric, fluorimetric, and immune-enzymatic methods. ALA lowered body weight and glucose metabolism parameters in insulin-resistant rats. ALA not only strengthened enzymatic antioxidant defense (by increasing superoxide dismutase, catalase and glutathione peroxidase activity) but also stimulated the synthesis of non-enzymatic GSH. ALA supplementation inhibited lipid peroxidation (decreased lipid hydroperoxides and malondialdehyde content) and prevented protein oxidation (by lowering advanced oxidation protein products concentration) in red muscle. ALA's multifactorial actions on muscle tissue also included inhibition of inflammation and apoptosis, requiring further research to elucidate its effects in metabolic diseases.

Effect of different dietary oil sources on the performance, egg quality and antioxidant capacity during the late laying period

This study investigated the effects of different dietary ratios of linseed and soybean oils on the performance, egg quality, and antioxidant capacity of late-phase laying hens. A total of 360 70-week-old Jinghong laying hens were randomly assigned to four groups of six replicates each, with 15 chickens per replicate. Diets with linseed oil to soybean oil ratios of 3:0 (T1), 2:1 (T2), 1:2 (T3), and 0:3 (T4) were fed for 4 weeks. No significant differences in egg weight, feed intake of laying hens, egg production, or feed-to-egg ratio (P > 0.05) were observed among the groups. Compared with the T4 group, the T2 group had a significantly higher number of 8–10 mm follicles. Moreover, albumen height and Haugh units were significantly higher in the T3 group than in the T4 group (P < 0.05), although significant differences were not observed among the T1, T2, and T3 groups. With an increase in linseed oil addition to the feed, the content of n-3 polyunsaturated fatty acids in chicken eggs significantly increased (P < 0.05). Compared to the T4 group, the addition of linseed oil to the diet significantly reduced the blood malondialdehyde content and increased the blood glutathione peroxidase (GSH-PX) and superoxide dismutase enzyme activity. The GSH-PX activity and total antioxidant capacity in the oviducts of the T3 group were significantly higher than those of the T4 group (P < 0.05). The protein expression levels of Nrf2, HO-1, and NQO-1 in the oviduct tissues were significantly higher in the T3 group than in the T4 group (P < 0.05). This study showed that a linseed oil to soybean oil ratio of 1:2 in the T3 group enhanced egg quality by reducing oxidative stress and improving the oviduct microenvironment.

Species-specific responses to di (2-ethylhexyl) phthalate reveal activation of defense signaling pathways in California sea lion but not in human skeletal muscle cells in primary culture.

Higher antioxidant defenses in marine than terrestrial mammals allow them to cope with oxidative stress associated with diving-induced ischemia/reperfusion. Does this adaptation translate to inherent resistance to other stressors? We analyzed oxidative stress indicators in cells derived from human and California sea lion (Zalophus californianus) skeletal muscle upon exposure to di (2-ethylhexyl) phthalate (DEHP). Human abdominal muscle biopsies were collected from healthy women undergoing planned cesarean surgery. California sea lion samples were collected postmortem from stranded animals. Skeletal muscle cells derived from each species were exposed to 1 mM DEHP for 13 days (n = 25) or maintained under control (untreated) conditions (n = 25). Superoxide radical (O2-) production, oxidative damage and antioxidant enzyme activities were measured using spectrophotometric methods. Gene expression was analyzed by RT-qPCR. DEHP exposure increased O2- production and superoxide dismutase (SOD) activity in both species. Glutathione S-transferase (GST) activity and protein carbonyls levels increased in human but not in California sea lion cells. In contrast, glutathione peroxidase (GPx) and catalase (CAT) activities increased in California sea lion but not in human cells exposed to DEHP. In human cells, DEHP increased microsomal GST1 and GST (κ, μ, θ, ω, and ᴢ), while suppressing 8-oxoguanine DNA glycosylase (OGG1), CAT, glutathione reductase (GR), and nuclear factor erythroid 2-related factor 2 (NRF2) expression, suggesting increased oxidative stress and phase two detoxification processes. In California sea lion cells, DEHP increased OGG1, NRF2, GPx2 and SOD3 expression, suggesting activation of antioxidant defenses, which potentially contribute to maintaining redox homeostasis, avoiding oxidative damage.

Growth, fat metabolism and hepatic health in largemouth bass fed varying fat-level diets

This 60-day experiment investigated the influences of growth, fat metabolism and hepatic health of largemouth bass (Micropterus salmoides) fed varying fat diets. 225 fish (34 ± 0.04 g) were divided into three groups and fed diets with fat levels of 10 % (Low-fat diet, LFD), 14 % (Medium-fat diet, MFD) and 18 % (High-fat diet, HFD), respectively. The results revealed that fish fed HFD exhibited significantly better protein efficiency ratio (PER) and lower feed conversion ratio (FCR) than LFD group (P<0.05), but survival rate (SR) and weight gain rate (WGR) were unaffected (P>0.05). Dietary fat levels significantly decreased hepatosomatic index (HSI) of fish (P<0.05), but visceral somatic index (VSI) and condition factor (CF) were unaffected (P>0.05). The contents of fat and ash in whole-body, and hepatic fat contents were increased with dietary fat levels (P<0.05), the contents of moisture and crude protein in whole-body and liver exhibited no substantial variations (P>0.05). Serum biochemical indexes and serum alanine aminotransferase (ALT) activity, liver glutathione peroxidase (GSH-Px) and catalase (CAT) activities were increased significantly with rising dietary fat levels (P<0.05), serum aspartate transaminase (AST) and liver superoxide dismutase (SOD) activities had no statistical differences (P>0.05). The expression of srebp-1 and acc in liver were down-regulated, but atgl, aco and bax were up-regulated with rising dietary fat contents (P<0.05). Caspase-3 exhibited a remarkable tendency of initially rising and then declining (P<0.05), the expression of fas, cpt-I, bcl-2 and the ratio of bcl-2/bax were unaffected (P>0.05). The histology of liver indicated the size and quantity of fat droplets increased with increment of dietary fat intake. Conclusion: the dietary fat levels of 14 %-18 % could be conducive to better growth of largemouth bass in this study.

Ameliorative effects of Edaravone against Valproic Acid-Induced kidney damage.

Valproic acid (VPA) is a well-known and increasingly documented antiepileptic drug that has been widely used in the treatment of epilepsy and/or epilepsy-related disorders. Prolonged clinical use of VPA has been reported to cause side effects such as nephrotoxicity. Edaravone (EDA) is a powerful free radical scavenger. The aim of the study was to investigate the protective effects of EDA against VPA-induced oxidative renal injury. Four experimental groups were formed by randomly assigning thirty-eight male Sprague Dawley rats. The first group, (Control Group, n = 8), consisted of healthy rats. The second group, (Group II, n = 10), comprised control rats given intraperitoneally EDA (30mg/kg/day) for seven days. The third group (Group III, n = 10) was administered intraperitoneally only VPA (500mg/kg/day) for seven days. The last group (Group IV, n = 10) was treated with VPA + EDA for seven days. On the 8th day, kidney tissues were immediately removed from rats. In kidney homogenates, reduced glutathione levels and Na/K+-ATPase, paraoxonase1 and prolidase activities were remarkably decreased while catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, myeloperoxidase, and xanthine oxidase activities and lipid peroxidation, protein carbonyl, advanced oxidized protein products, and hydroxyproline contents were notably elevated in VPA given group. Consistently, administration of EDA decreased renal degenerative changes seen in the kidney tissue of VPA given rats. Treatment with EDA in the VPA group significantly resulted in the recovery of both biochemical and histopathological alterations. As a result, EDA is potentially beneficial to revert oxidative renal damage induced by VPA.

Effect and mechanism of Donepezil hydrochloride on Alzheimer’s disease

Objective: To explore the effect and mechanism of donepezil hydrochloride on Alzheimer’s disease (AD).Methods: Thirty-six 3-month-old SD rats were selected as the research subjects and randomly divided into a normal control (NC) group and a model group. The model group was given continuous intraperitoneal injection of D-galactose solution (120 mg/kg/d) combined with aluminum trichloride (10 mg/kg/d) by gavage for 60 days. Morris water maze test was conducted to test the learning and memory abilities of the rats, and AD rats were selected. After modeling, AD rats were divided into a normal saline (NS) group and a drug treatment (DT) group. The DT group was given donepezil hydrochloride (1.0 mg/kg) by gavage intervention, and the NC group and the NS group were given equal volumes of physiological saline by gavage. After 4 weeks of intervention, Morris water maze test was conducted to detect the escape latency, the number of platform crossings and residence time in the target quadrant, the rats were euthanized, with serum and hippocampal tissues collected, and hippocampal tissue homogenate (10%) was prepared by using NS. Enzyme linked immunosorbent assay (ELISA) was used to detect the inflammatory and oxidative stress indicators in rat hippocampal tissues and serum, and hematoxylin eosin (HE) staining was used to observe pathological damage in rat hippocampal tissues.Results: Compared with the NC group, the NS group showed a significant increase in escape latency (p &lt; .05), a significant decrease in the number of platform crossings and residence time in the target quadrant (p &lt; .05), and a significant decrease in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum and hippocampal tissues (p &lt; .05). The content of malondialdehyde (MDA) was significantly increased (p &lt; .05), and the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly increased (p &lt; .05). Compared with the NS group, the DT group can significantly reduce the escape latency (p &lt; .05), increase the number of platform crossings and residence time in the target quadrant (p &lt; .05), significantly increase the activities of SOD and GSH-Px in serum and hippocampal tissues and reduce the content of MDA (p &lt; .05) and the levels of IL-6 and TNF-α (p &lt; .05). After intervention with donepezil hydrochloride, the number of neurons in the hippocampus were significantly increased.Conclusions: Donepezil hydrochloride can improve the learning and memory abilities of rats, reduce the levels of oxidative stress and inflammation in the brain and serum, and improve pathological damage in the hippocampus.

Lactobacillus reuteri TISTR 2736 alleviates type 2 diabetes in rats via the hepatic IRS1/PI3K/AKT signaling pathway by mitigating oxidative stress and inflammatory mediators.

This study investigated the beneficial effects of Lactobacillus reuteri TISTR 2736 on glucose homeostasis, carbohydrate metabolism, and the underlying mechanisms of its actions in type 2 diabetic (T2D) rats. A rat model of T2D was established by a combination of a high-fat diet and streptozotocin. The diabetic rats were treated daily with L. reuteri TISTR 2736 (2 × 108 CFU/day) for 30 days. Biochemical, histopathological, and molecular analyses were carried out to determine insulin signaling, carbohydrate metabolism, oxidative stress, and inflammation. The results demonstrated that treatment with L. reuteri TISTR 2736 significantly ameliorated fasting blood glucose and glucose intolerance, and improved insulin sensitivity indices in the diabetic rats. The hepatic histopathology was improved with L. reuteri TISTR 2736 treatment, which was correlated with a reduction of hepatic lipid profiles. L. reuteri TISTR 2736 significantly reduced glycogen content, fructose 1,6-bisphosphatase activity, and phosphoenolpyruvate carboxykinase 1 protein expression, and enhanced hexokinase activity in the diabetic liver. The downregulation of IRS1 and phosphorylated IRS1Ser307 and upregulation of PI3K and phosphorylated AKTSer473 proteins in the liver were found in the L. reuteri TISTR 2736-treated diabetic group. Furthermore, it was able to suppress oxidative stress and inflammation in the diabetic rats, as demonstrated by decreased malondialdehyde and protein levels of NF-κB, IL-6 and TNF-α, but increased antioxidant enzyme activities of superoxide dismutase, catalase, and glutathione peroxidase. By inhibiting oxidative and inflammatory stress, L. reuteri TISTR 2736 alleviated hyperglycemia and improved carbohydrate metabolism through activating IRS1/PI3K/AKT pathway in the T2D rats.

Cordyceps cicadae Extracts Exert Antiaging Effects by Activating the AMPK/SIRT1 Pathway in d-Galactose-Induced Aging Rats.

Cordyceps cicadae, a valuable traditional edible and medicinal resource, is recognized for its potential in slowing aging but has not been effectively exploited. This study aimed to explore antiaging activity and mechanisms of C. cicadae extracts (CCe). We used liquid chromatography-mass spectrometry to identify 23 CCe compounds and focused on quantifying six nucleoside components as quality markers. We also assessed the antiaging influences in d-galactose (d-gal)-induced aging rats. CCe improved learning memory deficits, enhanced organ indices, and mitigated oxidative brain damage caused by d-gal. CCe elevated superoxide dismutase and glutathione peroxidase activities, while downregulating malondialdehyde. Molecular analyses indicated the involvement of adenosine 5'-monophosphate-activated protein kinase/sirtuin 1 (AMPK/SIRT1) pathway in the antiaging mechanism of CCe. This study demonstrates the potential of CCe in mitigating d-gal-induced damage in aging rats, with the AMPK/SIRT1 pathway emerging as a regulatory axis. These findings contribute to the theoretical foundation for developing antiaging pharmaceuticals and functional foods using CCe, offering promising applications in aging-related contexts in succinct manner.

Ferroptosis exacerbates the clonal deletion of virus-specific exhausted CD8+ T cells.

During chronic infection or tumorigenesis, persistent antigen stimulation contributes to the exhaustion of CD8+ T cells. Nevertheless, exhausted CD8+ T (TEX) cells still preserve certain effector function, and maintaining a reservoir of exhausted cells is of vital importance for virus elimination and tumor eradiation. Despite considerable work interrogating the rejuvenation of TEX cells, mechanisms underpinning the clonal deletion of TEX cells remain largely unexplored over the past decade. In this study, we employed mouse models of LCMV infection to demonstrate that excessive accumulation of lipid peroxidation rendered virus-specific TEX cells to ferroptosis, which may correlate with enhanced mitochondria-derived oxidative stress and compromised activity of glutathione peroxidase 4 (GPX4). In addition, either incomplete or complete ablation of GPX4 resulted in exacerbated ferroptosis and aggravated shrunken population of virus-specific TEX cells. On the other hand, inhibiting ferroptosis via administration of a ferroptosis inhibitor or overexpression of GPX4 greatly rectified the cell loss of virus-specific TEX cells. Collectively, we disclosed ferroptosis as a crucial player in the clonal deletion of virus-specific TEX cells and stressed the intervention of ferroptosis as a promising approach to optimize the longevity of virus-specific TEX cells.

Pharmacotherapeutic potential of pratensein to avert metribuzin instigated hepatotoxicity via regulating TGF-β1, PI3K/Akt, Nrf-2/Keap-1 and NF-κB pathway

Metribuzin (MBN) is a selective herbicide that adversely damages the vital organs of the body including the liver. Pratensein (PTN) is a novel flavonoid that exhibits marvelous medicinal properties. This experimental trial commenced to elucidate the pharmacotherapeutic strength of PTN to counteract MBN provoked liver toxicity in rats. Thirty-six male albino rats (Rattus norvegicus) were categorized into four groups i.e., the control, MBN (133.33 mg/kg), MBN (133.33 mg/kg) + PTN (20 mg/kg) and PTN (20 mg/kg) alone treated group. Our findings revealed that MBN exposure promoted the expressions of Keap-1 as well as concentrations of ROS and MDA while reducing the gene expressions of Nrf-2 as well as activities of catalase (CAT), glutathione Peroxidase (GPx), glutathione reductase (GSR), heme oxygenase-1 (HO-1), superoxide dismutase (SOD) and glutathione (GSH) contents. The levels of albumin and total proteins were reduced whereas the levels of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were enhanced following the MBN administration. Moreover, the gene expression of transforming growth Factor–β1 (TGF-β1), matrix metallopeptidase-2 (MMP-2), matrix metallopeptidase-9 (MMP-9), collagen, type I, alpha 1 and type-3 alpha were escalated in response to MBN intoxication. Furthermore, MBN administration cause a sudden upregulation in the levels of NF-κB, IL-1β, TNF-α, IL-6 & COX-2. Besides, MBN exposure enhanced the gene expression of Bax and Caspase-3 while reducing the gene expression of PI3K, Akt and Bcl-2. Additionally, MBN exposure dysregulated the normal histology of liver. However, PTN treatment notably protected the hepatic tissues via regulating abovementioned dysregulations due to its marvelous ROS scavenging potential.

Optimizing selenium-enriched yeast supplementation in laying hens: Enhancing egg quality, selenium concentration in eggs, antioxidant defense, and liver health

This study evaluated the effects of selenium-enriched yeast (SY) supplementation at various levels on health and production parameters in laying hens, including egg production, egg quality, selenium (Se) concentrations in eggs, liver health, serum biochemical markers, antioxidant function, and immune responses. A total of 360 Hy-Line Brown hens (28 weeks old) were randomly assigned to four dietary groups with six replicates of 15 birds each, monitored over a 12-week feeding trial after a two-week acclimatization period. The dietary groups included a control (basal diet without selenium) and three SY-supplemented groups with Se levels of 0.3 mg/kg (SY03), 1.5 mg/kg (SY15), and 6.0 mg/kg (SY60). The results showed no significant effects of dietary SY on laying performance or feed efficiency (P > 0.05). However, the SY15 group showed significant improvements in egg quality, particularly in albumen height, Haugh Unit and yolk color (P < 0.05). Selenium concentrations in eggs, albumen, and yolk increased dose-dependently, with significant differences in the SY-supplemented groups (P < 0.001). Increased activities of liver enzymes including alanine transaminase, alkaline phosphatase, and aspartate transaminase, alongside elevated levels of uric acid were notable in the SY60 group (P < 0.05). In addition, histological analysis revealed significant hepatocyte degeneration and a higher liver organ index (P < 0.05), in the SY60 group. All of which suggests potential liver toxicity at higher selenium levels. Antioxidant capacity of the birds were significantly enhanced due to dietary supplementation of SY as indicated by increased serum levels of total antioxidant capacity, and activities of catalase, glutathione peroxidase, and superoxide dismutase (P < 0.05). Analysis of hepatic genes expression revealed that SY15 supplementation significantly upregulated key antioxidant-related genes (Nrf2, HO-1, CAT, and NQO1) and downregulated Keap1 expression (P < 0.05), suggesting strong activation of the antioxidant defense system. In conclusion, SY supplementation at 1.5 mg/kg improved egg quality, increased Se concentrations in eggs, and enhanced antioxidant capacity without affecting laying performance or liver health. This makes it a balanced approach to improving egg quality and poultry health. However, higher supplementation levels (6.0 mg/kg) resulted in liver damage, underscoring the importance of careful dosage consideration.

Resistance training improves functional capacities in women with multiple sclerosis: a randomized control trial

PurposeThis study aimed to investigate the effects of 12 weeks of resistance exercise training (RT) on oxidative status, muscle strength, functional capacity, quality of life (QoL), and fatigue in women with Multiple Sclerosis (MS).MethodsIn this randomized control trial (ethical code: SSRI.REC-1402-101; IRCT registration code: IRCT20120912010824N3, 07.09.2023), Iran) twenty-five women with relapsing- remitting MS (aged 18–45 years and expanded disability status scale (EDSS) ≤ 4) were randomly divided in two groups MS without resistance exercise (MS + non-RT; n = 13) and with RT (12 weeks/3 times per week/ 60–80% of 1RM) (MS + RT; n = 12). “Informed” consent was obtained from all participants. Then, fifteen healthy aged-matched women participated as a control group (HCON; n = 15). Blood serum levels of oxidative stress [malondialdehyde (MDA)] and antioxidant capacity [superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity] were obtained pre and post intervention. In addition, muscle strength by 5-RM test, functional capacity (for lower limb T25FWT, 2MWT, and 5STS tests and for Upper limb Manual dexterity of both hands with the (9-HPT) test and MSWS-12 questionnaire were also assessed over the same period. Also, Quality of life and fatigue were assessed pre- and post- intervention with by 31-MusiQoL questionnaire and FSMC questionnaire.ResultsRT led to improvements in muscle strength for leg extension, lying leg curl, bench press movements (P < 0.001, P < 0.001, P < 0.001, respectively). Moreover, compared with the MS + non-RT group, RT demonstrated increased functional capacity (Timed 25 ft Walk Test, Two-Minute Walk Test, 5-Time Sit-To-Stand Test, Twelve Item MS Walking Scale (P < 0.001, P < 0.001, P < 0.001, P < 0.001, respectively). Dexterity of the left hand but not the right hand also improved (P < 0.01, P = 0.057, respectively). Improvements were also found for fatigue and QoL (P < 0.01, P < 0.05). However, the mean changes of MDA, SOD and GPx noted in RT group were not statistically significant (P˃0.05, P˃0.05, P˃0.05, respectively).ConclusionsRT has positive effects on muscle strength, functional capacity, and quality of life while reducing fatigue in this population. However, markers of oxidative stress were not affected. When we consider the clear role in MS pathogenesis and progression, antioxidant increases in relation to a reduction in pro-oxidant capacity would have provided a positive and important clinical development for people with MS.

Polystyrene microplastics exposition on human placental explants induces time-dependent cytotoxicity, oxidative stress and metabolic alterations.

Microplastics (MPs) are environmental pollutants that pose potential risks to living organisms. MPs have been shown to accumulate in human organs, including the placenta. In this study, we investigated the biochemical impact of 5 μm polystyrene microplastics (PS-MPs) on term placental chorionic villi explants, focusing on cytotoxicity, oxidative stress, metabolic changes, and the potential for MPs to cross the placental barrier. Term placental chorionic explants were cultured for 24 hours with varying concentrations of PS-MPs, with MTT assays used to determine the appropriate concentration for further analysis. Cytotoxicity was assessed using the lactate dehydrogenase (LDH) release assay over a period of up to 72 hours. Reactive oxygen species formation and antioxidant activity were evaluated using biochemical assays. Metabolomic profiling was performed using proton nuclear magnetic resonance (1H NMR). Placental explants exposed to 100 μg/mL of PS-MPs showed a significant increase in cytotoxicity over time (p < 0.01). Levels of mitochondrial and total superoxide anion (p < 0.01 and p < 0.05, respectively) and hydrogen peroxide (p < 0.001) were significantly elevated. PS-MP exposure resulted in a reduction in total sulfhydryl content (p < 0.05) and the activities of antioxidant enzymes superoxide dismutase (p < 0.01) and catalase (p < 0.05), while glutathione peroxidase activity increased (p < 0.05), and the oxidized/reduced glutathione ratio decreased (p < 0.05). Markers of oxidative damage, such as malondialdehyde and carbonylated proteins, also increased significantly (p < 0.001 and p < 0.01, respectively), confirming oxidative stress. Metabolomic analysis revealed significant differences between control and PS-MP-exposed groups, with reduced levels of alanine, formate, glutaric acid, and maltotriose after PS-MP exposure. This study demonstrates that high concentrations of PS-MPs induce time-dependent cytotoxicity, oxidative stress, and alterations in the TCA cycle, as well as in folate, amino acid, and energy metabolism. These findings highlight the need for further research to clarify the full impact of MP contamination on pregnancy and its implications for future generations.