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Abstract: In this study, children with vitamin B12 deficiency anemia (V-B12DA) and control subjects were evaluated for erythrocyte glutathione peroxidase, catalase and superoxide dismutase enzyme activities, glutathione, malondialdehyde, serum total sialic acid, total antioxidant status, cobalt, chromium, copper, selenium, vanadium, zinc, iron, lead, magnesium, calcium, sodium, potassium, chloride, phosphorus levels, and the associations of these variables were assessed. The study included 50 children with V-B12DA and 50 control subjects. It was found that the V-B12DA group was significantly lower than the control group, with regard to the mean±the standard error of the mean levels of cobalt (0.089±0.009; 0.058±0.0063 μmol/L, p12 (427.20±21.45; 157.08±3.96 pg/mL, p12DA, significantly linear correlations were observed between cobalt – vitamin B12 (r=0.334; p=0.025), vanadium – MCV (r=0.315; p=0.017), vitamin B12 – MCV (r=−0.297; p=0.026). The findings of the study indicated that the levels of cobalt, vanadium significantly associated with traditional vitamin B12-deficiency parameters. Vitamin B12 and MCV should be measured together with cobalt, vanadium for monitoring the vitamin B12 deficiency anemia.

Palm-based oils (palm oil and kernel oil) and soybean oil have unique fatty acid and antioxidant profiles based on the compounds present in them. Hence, this study elucidated the antioxidant properties of crude palm oil (CPO), red palm oil (RPO), refined palm oil (RBD), palm kernel oil (PKO) and soybean oil (SBO) and the influence of dietary oils on blood lipid profiles, tissue fatty acid deposition and the expression of hepatic lipid and lipoprotein metabolism genes in laying hens. The oils were analyzed for color, beta-carotene, free fatty acid and acid value, phenolic content and lipid peroxidation. In an in vivo trial, 150 laying hens were allotted into five groups and supplemented with either CPO, RPO, RBD, PKO or SBO for 16 weeks. High antioxidant compounds present in palm oils help reduce the oxidation of oils. Dietary supplementation with palm oils, particularly CPO and RPO, contributed to the lower liver, serum and jejunal mucosal antioxidant enzyme activities. The antioxidant enzyme genes in the jejunal mucosa were downregulated in palm oils and PKO, but there was no difference between oils in antioxidant enzyme genes in the liver. In conclusion, dietary supplementation with oils with high antioxidant content contributed to protection against oxidation and was associated with a lower requirement for producing antioxidant enzymes.

Genistein is a natural isoflavonoid and has several pharmacological effects, such as antioxidant, antitumor activity, and improvement of glucose metabolism. The safety of intestinal anastomosis after ischemia-reperfusion (I/R) injury is a critical issue for surgeons. This experimental study aimed to investigate the effects of genistein on anastomotic healing after intestinal I/R injury.A total of 36 male Wistar Albino rats were divided into four groups: control, I/R, genistein, and genistein + I/R. The control group received segmental ileal resection and ileoileal anastomosis. The I/R group received resection + anastomosis after intestinal I/R. The genistein group was administered subcutaneous injection of 1 mg/kg genistein 12 h and 1 h before the procedure and received ileal resection + anastomosis. The genistein + I/R group received I/R + ileal resection + anastomosis after genistein injection. Anastomotic bursting pressure, hydroxyproline, superoxide dismutase, and glutathione peroxidase levels and histopathological wound healing scores of all rats were measured on postoperative day 5.The anastomotic bursting pressure was significantly higher in the genistein and genistein + I/R groups (P 0.001). Genistein increased the hydroxyproline concentration and the superoxide dismutase and glutathione peroxidase levels in the intestinal anastomosis (P 0.001). In histopathological assessment, the mean wound healing score was significantly higher in the genistein group than in the other groups (P 0.001).Genistein, with its anti-inflammatory and antioxidant properties, shows protective effects against increased oxidative stress after intestinal I/R injury and contributes positively to intestinal anastomotic healing.

Exposure to pesticides has been linked to an elevated risk of leukemia. The present research aimed to evaluate the relationship between organochlorine (OC) pesticides and biomarkers of oxidative stress in patients with leukemia. This work was conducted on 109 patients with leukemia and 109 healthy controls. The serum concentrations of seven derivatives of OCs including alpha-hexachlorocyclohexane (HCH), beta-HCH, gamma-HCH, 2,4-dichlorodiphenyltrichloroethane (DDT), 4,4-DDT, 2,4-dichlorodiphenyldichloroethylene (DDE), and 4,4-DDE along with acetylcholinesterase (AChE), glutathione peroxidase (GPx), superoxide dismutase (SOD), paraoxonase-1 (PON1), and catalase (CAT) activities as well as total antioxidant capacity (TAC), nitric oxide (NO), protein carbonyl (PC), and malondialdehyde (MDA) levels were measured in all the subjects. Levels of OCs were remarkably higher in patients with leukemia compared with the controls (p

Microplastic particles (MPs) are environmental pollutants that can cause varying levels of aquatic toxicity. Probiotics have been shown to reduce the negative effects of toxic substances. However, the protective effect of probiotics against the adverse effects of MPs has yet to be reported. The current study sought to determine the effects of the commercial probiotic AquaStar® Growout on polystyrene (PS)-MPs-mediated hepatic oxidative stress in Nile tilapia (Oreochromis niloticus). Fishes were assigned into four groups: the first group was the control, the second group was exposed to 1 mg/L of 0.5 μm PS-MPs, and the third and fourth groups were exposed to 1 mg/L of 0.5 μm PS-MPs and pre-fed with probiotics at levels of 3 g/kg and 6 g/kg diet, respectively. At the end of the experiment, probiotics administration reversed liver damage caused by the PS-MPs, reducing serum levels of malondialdehyde, aspartate aminotransferase, and alanine aminotransferase, and increasing the total antioxidant capacity. Furthermore, probiotics alleviated PS-MPs-induced oxidative stress by restoring antioxidant enzyme activities (superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase) and reducing oxidized glutathione and enhancing the redox state. Besides, probiotics supplementation decreased the transcriptional level of C-reactive protein and tumor necrosis factor-α following PS-MPs exposure. Furthermore, probiotics counteracted PS-MPs-associated reactive oxygen species production and mitogen-activated protein kinases (MAPKs) phosphorylation status. These findings suggested that probiotics could decrease liver damage caused by PS-MPs through their antioxidant properties and modulation of MAPK signaling pathways.

In diabetic nephropathy, hyperglycemia elevates albumin glycation and also results in increased plasma aldosterone. Both glycation and aldosterone are reported to cause oxidative stress by downregulating the NRF-2 pathway and thereby resulting in reduced levels of antioxidants and glycation detoxifying enzymes. We hypothesize that an interaction between aldosterone and glycated albumin may be responsible for amplified oxidative stress and concomitant renal cell damage. Hence, human serum albumin was glycated by methylglyoxal (MGO) in presence of aldosterone. Different structural modifications of albumin, functional modifications and aldosterone binding were analyzed. HEK-293 T cells were treated with aldosterone+glycated albumin along with inhibitors of receptors for mineralocorticoid (MR) and advanced glycation endproducts (RAGE). Cellular MGO content, antioxidant markers (nitric oxide, glutathione, catalase, superoxide dismutase, glutathione peroxidase), detoxification enzymes (aldose reductase, Glyoxalase I, II), their expression along with NRF-2 and Keap-1 were measured. Aldosterone binds to albumin with high affinity which is static and spontaneous. Cell treatment by aldosterone+glycated albumin increased intracellular MGO, MR and RAGE expression; hampered antioxidant, detoxification enzyme activities and reduced NRF-2, Keap-1 expression. Thus, the glycated albumin-aldosterone interaction and its adverse effect on renal cells were confirmed. The results will help in developing better pharmacotherapeutic strategies for diabetic nephropathy.

Dairy cattle are subjected to oxidative stress, inflammation, and altered immune function during the transition to lactation. The objective of this study was to evaluate the effects of a dietary Saccharomyces cerevisiae fermentation product (SCFP; NutriTek, Diamond V) on oxidative status, inflammation, and innate and adaptive immune responses during the transition period. Holstein cows were blocked by parity, expected calving date, and previous milk yield and then randomly assigned to treatment within block. Treatment was a control total mixed ration (n = 30) or SCFP total mixed ration (n = 34) fed from -29 ± 5 to 42 d relative to calving (RTC). Blood was sampled during wk -4, -2, 1, 2, and 5 and liver tissue at wk -3 and 2 RTC. Oxidative status was evaluated in plasma by retinol, α-tocopherol, and malondialdehyde concentrations, glutathione peroxidase activity, and Trolox equivalent antioxidant capacity, and in liver by mRNA abundance of nuclear factor E2-related factor 2 (NFE2L2), metallothionein 1E (MT1E), and glutathione peroxidase 3 (GPX3). Inflammation was evaluated in plasma by haptoglobin (HP) and serum amyloid A (SAA) concentrations and in liver by mRNA abundance of HP, serum amyloid A3 (SAA3), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB1). Innate immune response was measured by stimulated oxidative burst of polymorphonuclear cells (neutrophils) isolated from blood. Ovalbumin (OVA) was administered with adjuvant on d 7 and 21 RTC, and adaptive immune response was evaluated by serum anti-OVA IgG content on d 28 and 35. Mixed models were used to assess effects of treatment, time, parity, and all interactions. We previously reported that SCFP had limited effects on productivity in this cohort, although milk fat yield was transiently increased and subclinical ketosis incidence was increased. Supplementation with SCFP did not affect overall oxidative, inflammatory, or immune parameters. The only treatment × week interaction detected was for plasma α-tocopherol concentration, which tended to be greater in control cows during wk 2 RTC. A tendency for a treatment × parity interaction was detected for serum anti-OVA IgG titer, which tended to be greater for SCFP than for controls among primiparous cows. Plasma inflammatory biomarkers were not affected by SCFP but, unexpectedly, plasma HP was elevated at both prepartum time points and plasma SAA was elevated during wk -2 RTC compared with the expected increases in both biomarkers postpartum. In this cohort of transition cows with low disease incidence, SCFP generally did not affect oxidative, inflammatory, or immune parameters.

Arsenite (As) and fluoride (F), both of which are linked to a variety of human ailments, are regularly found in underground drinking water. Numerous studies have shown that As and/or F have negative impacts on testicular function and fertility. For this purpose, mouse Leydig cells, the main cells responsible for the generation and regulation of steroid hormones such as testosterone, were used to reveal the effects of individual and combined exposure of As and F on the steroidogenic pathway in the male reproductive system. Leydig cells were treated with 0.39 μM (50 ppb) As and 0.0476 mM (2 ppm) F alone and in combination for 24 h. The findings revealed that As and/or F exposure induced oxidative stress and apoptosis in Leydig cells and altered antioxidant equilibrium of the cells by reducing superoxide dismutase, catalase, glutathione peroxidase. Additionally, individual and combined administration of As and/or F significantly supressed the expression of both steroidogenic enzymes and the genes encoding these enzymes. In conclusion, this study showed that exposure to As and F at environmentally relevant concentrations dispersed by water decreased testosterone production in Leydig cells, an important cell of the male reproductive system. The deleterious effects of even the lowest concentrations of As and F elements that can reach humans from the environment on the Leydig cell, and therefore on male infertility, emphasize necessity new safe limits for these elements.

To study differences in oxidative stress markers and antioxidants among patients with bipolar depression (BPD) and unipolar depression (UPD).Data sources. Electronic MEDLINE/PubMed/Cochrane Library/Scopus/TripDatabase database search until 30/06/2021.Included were articles comparing antioxidant or oxidative stress markers between adults with BPD or UPD and healthy controls (HCs).Two authors extracted data independently. Random effects meta-analysis, calculating standardized mean differences for results from ≥3 studies.Oxidative stress markers reported in 40 studies -1 published repeatedly- (UPD, studies = 30 n = 3072; their HCs, n = 2856; BPD, studies = 11 n = 393; their HCs, n = 540; with 1 study reporting on both UPD and BPD) included thiobarbituric acid reactive substances (TBARS), antioxidant uric acid and antioxidant-enhancing enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPX). Compared with HCs, UPD and BPD were associated with significantly higher levels of TBARS, without differences between UPD and BPD (P = 0.11). Compared with HCs, UPD and BPD did not differ regarding the activity of the CAT (P = 0.28), SOD (P = 0.87) and GPX (P = 0.25) enzymes. However, uric acid levels were significantly higher vs HCs in BPD than in UPD among adult patients (P = 0.004). Results were heterogenous, which, for some parameters, decreased after stratification by the blood source (serum, plasma red blood cells, whole blood).The main limitations are the small number of studies/participants in the BPD subgroup, and heterogeneity of the results.Both BPD and UPD may be associated with an impaired oxidative stress balance, with significantly higher uric acid levels vs. HCs in UPD than in BPD.

In this study, oxidative stress was investigated as the possible mechanism of action of organochlorine pesticides (OCPs) and organophosphorus pesticides (OPPs) in primary brain tumors (PBT). The levels of seven OCP residues and enzymatic antioxidant biomarkers including erythrocyte acetylcholinesterase (AChE), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and paraoxonase-1 (PON-1) along with non-enzymatic oxidative biomarkers including malondialdehyde (MDA), protein carbonyl (PC), total antioxidant capacity (TAC), and nitric oxide (NO) were measured in blood samples of 73 patients with PBT and 104 healthy controls. A significant association was found between farming activities and PBT (55% of patients were engaged in farming activities while 45% had no farming experience). The mean levels of β-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 4,4 DDT, MDA, PC, NO, SOD, CAT, and GPx were significantly higher in PBT patients, whereas the levels of TAC, PON-1, and AChE were significantly lower in these patients. Regression analysis showed that PBT was correlated with β-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, and 4,4 DDT. Based on these results, it can be concluded that OCPs and OPPs may play a role in PBT development through the formation of reactive oxygen species (ROS) and promoting oxidative stress.

Iron [Fe(II)] and copper [Cu(II)] overloads in rat brain are associated with oxidative stress and damage. The purpose of this research is to study whether brain antioxidant enzymes are involved in the control of intracellular redox homeostasis in the brain of rats male Sprague-Dawley rats (80-90 g) that received drinking water supplemented with either 1.0 g/L of ferrous chloride (n = 24) or 0.5 g/L cupric sulfate (n = 24) for 42 days. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione transferase (GT) activities in brain were determined by spectrophotometric methods and NO production by the content of nitrite concentration in the organ. Chronic treatment with Fe(II) and Cu(II) led to a significant decrease of nitrite content and SOD activity in brain. Activity of NADPH oxidase increased with Cu(II) treatment. Concerning Fe(II), catalase and GT activities increased in brain after 28 and 4 days of treatment, respectively. In the case of Cu(II), catalase activity decreased whereas GT activity increased after 2 and 14 days, respectively. The regulation of redox homeostasis in brain involves changes of the activity of these enzymes to control the steady state of oxidant species related to redox signaling pathways upon Cu and Fe overload. NO may serve to detoxify cells from superoxide anion and hydrogen peroxide with the concomitant formation of peroxynitrite. However, the latest is a powerful oxidant which leads to oxidative modifications of biomolecules. These results suggest a common pathway to oxidative stress and damage in brain for Cu(II) and Fe(II).

Multiple sclerosis (MS) and its animal models are characterized by cellular inflammation within the central nervous system (CNS). The sources and consequences of this inflammation are currently not completely understood. Critical signs and mediators of CNS inflammation are reactive oxygen species (ROS) that promote inflammation. ROS originate from a variety of redox-reactive enzymes, one class of which catalyses oxidative protein folding within the endoplasmic reticulum (ER). Here, the unfolded protein response and other signalling mechanisms maintain a balance between ROS producers such as ER oxidoreductin 1α (Ero1α) and antioxidants such as glutathione peroxidase 8 (GPx8). The role of ROS production within the ER has so far not been examined in the context of MS. In this manuscript, we examined how components of the ER redox network change upon MS and experimental autoimmune encephalomyelitis (EAE). We found that unlike GPx8, Ero1α increases within both MS and EAE astrocytes, in parallel with an imbalance of other oxidases such of GPx7, and that no change was observed within neurons. This imbalance of ER redox enzymes can reduce the lifespan of astrocytes, while neurons are not affected. Therefore, Ero1α induction makes astrocytes vulnerable to oxidative stress in the MS and EAE pathologies.

Acute myocardial infarction (AMI) leads to anoxia and ischemia of cardiomyocytes, followed by apoptosis. This study investigated the protective effect of ginsenoside Rg1 (Rg1) on myocardial ischemia injury in rats with AMI. Rats were randomly divided into five groups: group A (blank control group), group B (hypoxia/reoxygenation group), group C (hypoxia/reoxygenation + 10 mg/L Rg1), group D (hypoxia/reoxygenation + 20 mg/L Rg1) and group E (hypoxia/reoxygenation + 40 mg/L Rg1). The survival rate, apoptosis rate, expression of cyclin-dependent kinase 4 (CDK4), fibroblast growth factor 9 (FGF9), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), microvessel density and myocardial infarction area of rats in each group were compared. The expressions of CDK4 and FGF9, the contents of SOD and GSH-Px in groups C, D and E injected with Rg1 were significantly promoted compared to group B without Rg1 injection (P lt; 0.05). The survival rate of myocardial cells was significantly increased while the apoptosis rate was significantly decreased in group C, D, E compared to group B (P lt; 0.05). On the 3rd, 7th and 10th day following Rg1 treatment, the infarct area of E group was significantly decreased in three groups C, D, E, and the microvessel density of infarct area was significantly increased compared with group B (P lt; 0.05). So, Rg1 can improve the survival rate of myocardial cells, reduce the apoptosis rate and the area of myocardial infarction, and increase the microvessel density of infarct area, thus playing a protective role in ischemic myocardial cells of AMI rats.

Background. Silver nanoparticles (AgNPs) utilization is becoming increasingly popular. The existing investigation evaluates the ameliorative impact of eugenol (Eug) against the toxic influences of AgNPs on rats’ liver. Methods. Sixty adult male rats were enrolled equally into control, Eug (100 mg kg-1 orally), AgNPs-low dose (1 mg kg-1 i.p), AgNPs-high dose (2 mg kg-1 i.p), Eug + AgNPs-low dose ( 100 mg k g − 1 orally + 1 mg k g − 1 i . p ), and Eug + AgNPs high dose ( 100 mg k g − 1 orally + 2 mg k g − 1 i . p ). All the groups were treated daily for 30 days, subsequently serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total protein, total albumin, lactate dehydrogenase (LDH), total oxidative capacity (TOC), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), total antioxidant capacity (TAC), and interleukin 6 (IL-6) levels were measured; hepatic tissues superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and glutathione peroxidase (GPx) levels were evaluated; histopathology and histomorphometry were documented in the liver of all groups; and Bcl-2, P53, Caspase-3, and TNF-α reactive proteins were also immunohistochemically detected. Results. AgNPs significantly triggered oxidative stress in hepatic tissues, characterized by elevated levels of AST, ALT, ALP, LDH, TOC, MDA, TNF-α, and IL-6 correlating with considerable decline in total protein, total albumin, TAC, SOD, CAT, GSH, and GPx. These changes were paralleled with histopathological alterations remarkable by devastation of the ordinary hepatic structure, with decrease in the numbers of normal hepatocytes, elevation in the numbers of necrotic hepatocytes, periportal and centrilobular inflammatory cells, deteriorated Kupffer cells, and dilated/congested central and portal veins. Alongside, a marked diminution in Bcl-2 immunoreactivity and a significant elevation in P53, Caspase-3, and TNF-α immunoreactivities were recorded. Supplementation of AgNPs-treated animals with Eug reversed most of the biochemical, histopathological, and immunohistochemical changes. Conclusion. This study proposed that Eug has an ameliorative effect against AgNPs-induced hepatotoxicity.

Anthocyanins are known for their therapeutic efficacy for many human diseases, including cancer. After ingestion, anthocyanins degrade due to oxidation and enzymatic breakdown, resulting in reduced therapeutic efficacy. Direct delivery to target tissues and entrapment of anthocyanins increases their stability, bioavailability, and therapeutic efficacy. The objective of the present study was to develop a direct delivery system of anthocyanins into pulmonary tissues via encapsulated nanocarriers. A cyanidin-3-O-glucoside (C3G)-rich anthocyanin extract was prepared from well-ripened haskap (Lonicera caerulea L.) berries (HB) and encapsulated in three different polymeric nanocarrier systems: polyethylene glycol-poly(lactide-co-glycolide), maltodextrin, and carboxymethyl chitosan (CMC). The anthocyanin encapsulation efficiency was significantly higher in CMC (10%) than in the other two polymers. The cytotoxicity and cytoprotective effect of HB anthocyanin-encapsulated CMC (HB-CMC, 4 μg of C3G equivalent anthocyanin in 2 mg/mL nanoparticle) and anthocyanin-free CMC (E-CMC, 2 mg/mL) were tested for cytotoxicity using human normal lung epithelial BEAS-2B cells. The CMC nanoparticles were not cytotoxic for BEAS-2B cells. The HB-CMC nanoparticles reduced carcinogen-induced oxidative stress in BEAS-2B cells and restored the expression of superoxide dismutase and glutathione peroxidase enzymes. The HB-CMC nanoparticles also reduced carcinogen-induced DNA single-strand breaks and alkaline-labile sites but not the double-strand breaks. The E-CMC, HB-CMC (28 μg C3G equivalent/mouse/day for six days), or the same dose of free HB anthocyanin was administered to A/JCr mice through a nose-only passive inhalation device. C3G and its metabolites, cyanidin, peonidin-3-O-glucoside, and cyanidin-3-O-glucuronide, were detected by UPLC/ESI/Q-TOF-MS in the lungs of mice after one hour of exposure. Therefore, the CMC could be a promising noncytotoxic candidate to encapsulate HB anthocyanin. Direct delivery of anthocyanin to lung tissues enhances tissue retention, slows phase 2 metabolism, and improves therapeutic efficacy.

Incomplete combustion of wood releases toxic chemicals. Exposure to these chemicals during charcoal production can modulate redox status of cellular system which may further lead to genomic instability and of antioxidant enzymes. Genetic polymorphism may alter the functioning properties of these enzymes and modulate the response to oxidative stress.In this study, we analyzed the link between genetic polymorphism and enzyme activity for antioxidant enzymes: MnSOD and GPx-1 in charcoal workers and control population. This study included 77 charcoal workers and 79 demographically matched healthy control subjects. This association was studied using multiple linear regression, adjusted for confounding factors viz. age, consumption habits and exposure duration.SOD activity was lower for TT genotype (3.47 ± 0.66; 5.92 ± 1.08) versus CC genotype (3.47 ± 0.66; 6.67 ± 1.60) in control and charcoal workers respectively. Significant lower GPx-1 activity was found in leu/leu genotype (7.25 ± 0.38; 3.59 ± 0.57) when compared to pro/pro genotype (7.78 ± 0.59; 4.28 ± 0.71) and pro/leu genotype (8.48 ± 0.34; 4.30 ± 0.76) in control population and charcoal workers respectively. A significant difference in the levels of 1-Hydroxypyrene (biomarker of exposure) and SOD and GPx-1 activity (biomarkers of oxidative stress) was evident in exposed group in comparison to the control one.Collectively, our findings suggested that PAH influenced the mode of action of SOD and GPx-1 which were impacted by polymorphism in SOD and GPx-1 gene. Hence, polymorphism of MnSOD and GPx-1 genes were found to play a modulatory role in human susceptibility to oxidative damage induced by wood smoke in charcoal workers.

Acute ammonia toxicity suppresses the immune function and enhances the inflammatory pathways in Nile tilapia. The aim of this study was to compare the effect of Bacillus strains probiotic mixture (BS) or Yucca shidigera liquid extract (YSE) alone or their combination in water treatment and in reliving toxicity of an acute ammonia exposure in Nile tilapia through the assessment of fish immune response, inflammatory pathway, oxidative stress response with respect to the histopathological changes, gene expression, enzymes levels and phagocytosis. Five groups were used; the 1st and 2nd groups fed the basal diet; the 3rd group fed basal diet with BS in water, 4th group fed basal diet and supplemented with YSE in water and 5th group received a combination of BS and YSE. After two weeks of treatments, the 2nd, 3rd, 4th, and the 5th groups were exposed to acute ammonia challenge for 72 h. Fish exposed to ammonia displayed significant decreases in RBCs, Hb, PCV, WBCs, phagocytic activity (PA) and index (PI), lysozyme activities and serum antioxidant enzymes (glutathione peroxidase (GPX) and catalase (CAT)). Also, a significant increase in Malondialdehyde (MDA), degenerative changes in the gills, hepatopancrease and spleen associated with an elevated un-ionized ammonia level. A significant restoration of the hematological parameters was observed with the use of BS, YSE or their combination. Additionally, they improved the innate immunity, antioxidant responses, and histopathological changes. At transcriptomic level, ammonia toxicity significantly lowered the mRNA transcription levels of Nuclear erythroid 2-related factor 2 (Nrf2), quinone oxidoreductase 1 (NQO-1), Heme oxygenase 1 (HO-1) and Heat shock proteins (HSP70). While nuclear factor kappa β (NFкβ), Tumor necrosis factor α (TNF-α), Interleukin 1β (IL-1β), and Interleukin 8 (IL8), transcription levels were increased. Interestingly, BS and YSE and their combination significantly increased the expression of these genes with the highest levels reported with BS and YSE combination. We observed that, the most pronounced restoration of some important inflammatory and immune related genes close to the control level was observed when BS-YSE mix was used. Furthermore, a restored water pH, and a maintained ammonia level to the control level were observed in this group. Otherwise, equal effects for the three treatments were observed on the assessed parameters. We recommend the used of BS-YSE mix for water ammonia treatment and relieving ammonia toxicity in fish.

Background: Shortage of oxygen is a common condition for residents of high-altitude (HA) areas. In mammals, hemoglobin (Hb) has four derivatives: oxyhemoglobin (Hb-O2), carboxyhemoglo-bin (Hb-CO), sulfhemoglobin (Hb-S), and methemoglobin (Met-Hb). In HA areas, aberrant physio-logical performance of blood hemoglobin is well-established. Objective: The study aimed to investigate the influence of 30 days of HA residence on rabbits' total Hb, Hb derivatives, Hb autooxidation rate, and antioxidant enzymes in comparison to low-altitude control rabbits. Further, the study aimed to investigate the effect of antioxidant-rich Angelica archan-gelica and/or Ginkgo biloba extracts on the same parameters in HA-resident rabbits. Methods: Rabbits subjected to 30 days of HA residence were compared to low-altitude control rabbits. HA-residence rabbits were then orally administered 0.11 g/kg b.wt. of Angelica archangelica and/or Ginkgo biloba extract for 14 days. Hb derivatives and Hb autooxidation rate were measured spectro-photometrically. Antioxidant enzymes were estimated using specialized kits. Results: Compared to low-altitude rabbits, 30-day HA-residence rabbits showed a noticeable increase (p Conclusion: The findings suggest that functional Hb levels may be recovered by oral administration of A. archangelica, G. biloba, or combined treatments. In conclusion, oxidative stress due to living in HA areas may be avoided by supplementation with natural antioxidants.

Individual and combined efficacy of chitooligosaccharides (COS) and alginic acid (AA) at 1 g, 2 g, and 3 g per kg diet was assessed on growth and disease resistance in silver carp (Hypophthalmichthys molitrix) against Edwardsiella ictaluri. Growth parameters including specific growth rate (SGR), weight gain (WG), and feed conversion rate (FCR) were significant in fish fed 2 g and 3 g kg

Vascular dementia (VaD) is the second most common form of dementia globally, yet there are no efficient treatments. Naringenin, a natural flavonoid, exerts antioxidative, anti-inflammatory, and neuroprotective properties; however, its potential effect on VaD remain unclear. Herein, the purpose of present study was to elucidate whether naringenin attenuates cognitive dysfunction in VaD via inhibiting hippocampal oxidative stress and inflammatory response, and promoting N-methyl-D-aspartate receptors (NMDARs) signaling pathway. A rat model of VaD was established by permanent bilateral common carotid artery occlusion [2-vessel occlusion (2VO)]. Behavioral performance analyses results revealed that administration of naringenin improves cognitive impairment in rats with VaD according to the new object recognition test and the Morris water maze test. In addition, naringenin attenuated hippocampal oxidative stress by reducing reactive oxygen species generation, decreasing malondialdehyde content and recombinant reactive oxygen species modulator 1 (Romo-1) expression, and increasing superoxide dismutase and glutathione peroxidase activities in the hippocampus of VaD rats. Moreover, naringenin decreased the proinflammatory cytokines (IL-1β, IL-6, and TNF-α) levels and increased the anti-inflammatory cytokines (IL-10 and IL-4) levels in the hippocampus of 2VO surgery-treated rats, attenuating hippocampal inflammatory response during VaD. Furthermore, naringenin promoted synaptophysin (SYP), postsynaptic density protein 95 (PSD95), N-methyl-Daspartic acid receptor 1 (NR1) and N-methyl-D-aspartate receptor subunit 2B (NR2B) expressions levels in hippocampus of VaD rats. Collectively, these findings indicated that naringenin mitigates cognitive impairment in VaD rats partly via inhibiting hippocampal oxidative stress and inflammatory response and restoring NMDARs signaling pathway.

Objective Breast cancer causes death in women. Thymus Caramanicus Jalas (TCJ) as a polyphenolic plant has an antiproliferative effect. Accordingly, this investigation studied the TCJ extract anti-tumor effects in a breast cancer model. Methods Twenty-four female BALB/c mice were used in 4 groups including (1) breast cancer (control); (2), (3) and (4) breast cancer + 100, 300 and 500 mg/kg of TCJ extract (once daily for 20-days after breast tumor induction). The breast tumour was induced by 4T1 cell carcinoma injection. Then tumor size and weight were measured. Tumor necrosis factor-α (TNF-α), nuclear factor κ-B (NF-κB), interleukin-6 (IL-6) as inflammatory markers and also Bcl-2, Bax, cytosolic cytochrome-c, apoptosis-inducing factor, and cleaved caspase-3 as biochemical apoptosis markers were evaluated in tumor tissue with western blotting analysis. Also, malondialdehyde (MDA) concentration, hydrogen peroxidase (H2O2), catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were exanimated. Key findings Treatment with TCJ extract (500 mg/kg) decreased the tumor volume, tumor weight, GPx, SOD, and catalase enzyme activity versus the control group (P < 0.05). Also, TCJ (500 mg/kg) extract increased MDA, H2O2, inflammatory and apoptosis markers versus control (P < 0.05). Conclusions Current study showed that TCJ can induce anti-tumour effects via promoting inflammation, apoptosis, and oxidative stress in breast tumour tissue.

Liupao tea (fermented dark tea) may improve the active function of hyperlipidemia. Utilizing a hyperlipidemia Sprague-Dawley model and UPLC-MS/MS metabolomics, we examined how the effect of Liupao and green tea extracts on hyperlipidemia and antoxidant enzyme levels and compared their constituents. The results showed that the two types of tea could reduce the levels of total cholesterol (TC), total triglyceride, and low-density lipoprotein cholesterol (LDL-C); increase the contents of bile acids and cholesterol in feces; and improve catalase and glutathione peroxidase (GSH-Px) activities. Compared with the model control group, Liupao tea effectively reduced TC and LDL-C levels by 39.53% and 58.55% and increased GSH-Px activity in the liver by 67.07%, which was better than the effect of green tea. A total of 93 compounds were identified from two samples; the amounts of alkaloids and fatty acids increased compared with green tea, and ellagic acid, hypoxanthine, and theophylline with relatively high contents in Liupao tea had a significantly positive correlation with antihyperlipidemic and antioxidant effects. Therefore, Liupao tea had better antihyperlipidemic and antioxidant activities in vivo than green tea, which might be related to the relatively high content of some active substances.

Salvianolic acid B (SalB) can attenuate myocardial ischemia/reperfusion (I/R) injury, but the mechanisms are not entirely known. Our study investigates if SalB protects cardiomyocytes against I/R injury by regulating Tripartite motif (TRIM) protein. AC16 cardiomyocytes were treated with I/R, and then with SalB (10, 25 and 50 μM) for 24 h, while control cells were cultured under normal conditions. Female Sprague-Dawley rats were subjected to I/R injury, and then intravenously injected with 20, 40, or 60 mg/kg SalB or saline, as a control, rats received sham operation and saline injection. Upon treatment, apoptotic rate, reactive oxygen species (ROS), and malondialdehyde (MDA) were increased 10-, 3.8-, and 1.3-fold, respectively, while superoxide dismutase (SOD) activity was reduced by 62.1% compared to control cells. I/R treatment elevated the mRNA and protein expression of TRIM8. SalB treatment remarkably abolished the above-mentioned effects of I/R treatment. TRIM8 knock-down could partially alleviate I/R-induced myocardial injury. TRIM8 overexpression promoted cardiomyocyte injury, which was alleviated by SalB. Moreover, TRIM8 negatively regulated protein expression of antioxidant enzyme glutathione peroxidase 1 (GPX1). TRIM8 protein interacted with GPX1 and TRIM8 overexpression promoted GPX1 ubiquitnation. GPX1 knock-down abolished the protective effects of SalB on I/R-injured cardiomyocytes. Our in vivo experiments confirmed the effects of SalB on I/R-induced myocardial injury. SalB protected cardiomyocytes from I/R-induced apoptosis and oxidative stress in vitro and in vivo, which was partly mediated by the TRIM8/GPX1 axis. This suggests that down-regulation of TRIM8 expression may ameliorate I/R-induced myocardial injury.

Probiotics have the potential to be used in the prevention of Clostridioides difficile infection (CDI). In this study, selenium (Se)-enriched Bifidobacterium breve YH68-Se was obtained under optimal culture conditions with single-factor and response surface optimization. The overall environmental resistance of YH68-Se was superior to that of the parental strain YH68, mainly reflected in the substantial improvement of antioxidant activity and gastrointestinal tolerance. YH68-Se dramatically inhibited C. difficile growth, spore, biofilm, toxin production, and virulence gene expression, rapidly disrupted C. difficile cell membrane permeability and integrity, and altered the membrane proton motive force (PMF), induced a large outflow of intracellular substances and eventually caused bacterial death. The main factor inducing this process originated from the lactic acid (LD) in YH68-Se. In addition, the LD production of YH68 increased with increasing selenite concentration and was accompanied by enhanced activities of thioredoxin reductase (TrxR), glutathione peroxidase (GSH-Px), and increased concentration of autoinducer-2 (AI-2), which may be the crucial factors contributing to the outstanding probiotic properties of YH68-Se and their potent antagonism of C. difficile. KEY POINTS: • Compared with the parental strain B. breve YH68, the environmental resistance of YH68-Se was improved. • YH68-Se was able to produce more lactic acid, which suppressed the important physiological activities of C. difficile and rapidly disrupted their cell membrane structures. • Sodium selenite in the suitable concentration range gradually increases the yield of lactic acid and phenylacetic acid, increased the concentration of autoinducer-2, and enhanced the activities of antioxidant enzymes TrxR and GSH-Px in YH68.

Tiger pufferfish (Takifugu rubripes) is one of Asia's most economically valuable aquaculture species. However, winter production of this species in North China is limited by low water temperature and unavailability of high-quality feed, resulting in high mortality and low profitability. Therefore, the aim of this study was to evaluate the effect of feeding frequency (F1: one daily meal; F2: two daily meals; F3: four daily meals; F4: continuous diurnal feeding using a belt feeder) on the growth performance, plasma biochemistry, digestive and antioxidant enzyme activities, and expression of appetite-related genes in T. rubripes (initial weight: 266.80 ± 12.32 g) cultured during winter (18.0 ± 1.0 °C) for 60 days. The results showed that fish in the F3 group had the highest final weight, weight gain rate, specific growth rate, survival rate, and best feed conversion ratio. Additionally, daily feed intake increased significantly with increasing feeding frequency. The protein efficiency and lipid efficiency ratios of fish in the F3 group were significantly higher than those of fish in the other groups. Furthermore, total cholesterol, triglycerides, and glucose levels increased with increasing feeding frequency, peaking in the F2 group and decreasing under higher feeding frequencies. The antioxidant (superoxide dismutase, catalase, glutathione, and glutathione peroxidase) and digestive (trypsin, amylase, and lipase) enzyme activities of fish in the F1 group were significantly higher than those of fish in the F3 and F4 groups. Additionally, there was a decrease in orexin expression with increasing feeding frequency. In contrast, the expression levels of tachykinin, cholecystokinin, and leptin increased with increasing feeding frequency, peaking in the F4 group. Overall, the findings of this study indicated that a feeding frequency of four meals per day was optimal for improved growth performance of pufferfish juveniles cultured during winter.

The herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) is widely used to control broadleaved weeds and has been associated with male infertility. We studied the molecular mechanisms of 2,4-D induced male reproductive system damage and the protective effects of Lycium barbarum polysaccharides (LBP) using Sprague Dawley rats and TM4 cells. Treatment with 2,4-D caused architectural and functional changes in the testis, including collapsed and atrophied seminiferous tubules with reduced number of spermatozoa, scarce sperm in the epididymal duct, low levels of serum testosterone, decreased superoxide dismutase and glutathione peroxidase activity, high malondialdehyde content, and increased apoptosis in the testis and epididymis. The expression of Fas, FasL, FADD, Pro-caspase-8, Cleaved-Caspase-8, Pro-Caspase-3, and Cleaved-Caspase-3 were significantly increased in the testicular tissue of 2,4-D-treated rats. The proliferative activity of TM4 cells decreased with an increase in dose and time of 2,4-D exposure, along with enhanced Fas/Fas ligand expression and a decreased concentration of inhibin B in TM4 cell culture medium. Depletion of Fas by specific shRNA transfection reversed the effects of 2,4-D in TM4 cells, further confirming the involvement of death receptor pathway in 2,4-D-mediated apoptosis of sertoli cells. Treatment with LBP also reversed the effects of 2,4-D in testicular cells, resulting in improved cell architecture along with enhanced proliferative capacity. Moreover, in response to LBP treatment of Sertoli cells, the content of inhibin B increased, the level of reactive oxygen species and malondialdehyde decreased, the activities of superoxide dismutase and glutathione peroxidase increased, and the rate of apoptosis as well as the expression of Fas/Fas ligand signaling pathway proteins decreased.

High-dose ascorbate (vitamin C) has shown promising anticancer activity. Two redox mechanisms have been proposed: hydrogen peroxide generation by ascorbate itself or glutathione depletion by dehydroascorbate (formed by ascorbate oxidation). Here we show that the metabolic effects and cytotoxicity of high-dose ascorbate in vitro result from hydrogen peroxide independently of dehydroascorbate. These effects were suppressed by selenium through antioxidant selenoenzymes including glutathione peroxidase 1 (GPX1) but not the classic ferroptosis-inhibiting selenoenzyme GPX4. Selenium-mediated protection from ascorbate was powered by NADPH from the pentose phosphate pathway. In vivo, dietary selenium deficiency resulted in significant enhancement of ascorbate activity against glioblastoma xenografts. These data establish selenoproteins as key mediators of cancer redox homeostasis. Cancer sensitivity to free radical-inducing therapies, including ascorbate, may depend on selenium, providing a dietary approach for improving their anticancer efficacy. Significance: Selenium restriction augments ascorbate efficacy and extends lifespan in a mouse xenograft model of glioblastoma, suggesting that targeting selenium-mediated antioxidant defenses merits clinical evaluation in combination with ascorbate and other pro-oxidant therapies.

Ginseng is known to possess anti-aging potential. Klotho mutant mice exhibit phenotypes that resemble the phenotype of the human aging process. Similar to Klotho deficient mice, patients with chronic kidney disease (CKD) suffer vascular damage and cognitive impairment, which might upregulate the angiotensin II AT1 receptor. Since AT1 receptor expression was more pronounced than endothelin ET-1 expression in the hippocampus of aged Klotho deficient (±) mice, we focused on the AT1 receptor in this study. Ginsenoside Re (GRe), but not ginsenoside Rb1 (GRb1), significantly attenuated the increase in AT1 receptor expression in aged Klotho deficient mice. Both GRe and the AT1 receptor antagonist losartan failed to attenuate the decrease in phosphorylation of JAK2/STAT3 in aged Klotho deficient (±) mice but significantly activated nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling. Both GRe and losartan attenuated the increased NADPH oxidase (NOX) activity and reactive oxygen species (ROS) in aged Klotho deficient mice. Furthermore, of all the antioxidant enzymes, GRe significantly increased glutathione peroxidase (GPx) activity. GRe significantly attenuated the reduced phosphorylation of ERK and CREB in GPx-1 knockout mice; however, genetic overexpression of GPx-1 did not significantly affect them in aged mice. Klotho-, Nrf2-, and GPx-1-immunoreactivities were co-localized in the same cells of the hippocampus in aged Klotho wild-type mice. Both the GPx inhibitor mercaptosuccinate and Nrf2 inhibitor brusatol counteracted the effects of GRe on all neurobehavioral impairments in aged Klotho deficient (±) mice. Our results suggest that GRe attenuates all alterations, such as AT1 receptor expression, NOX-, ROS-, and GPx-levels, and cognitive dysfunction in aged Klotho deficient (±) mice via upregulation of Nrf2/GPx-1/ERK/CREB signaling.

Hypoxia (2 mg O

Glutathione peroxidase 1 (GPx1) is an important cellular antioxidant enzyme that is found in the cytoplasm and mitochondria of mammalian cells. Like most selenoenzymes, it has a single redox-sensitive selenocysteine amino acid that is important for the enzymatic reduction of hydrogen peroxide and soluble lipid hydroperoxides. Glutathione provides the source of reducing equivalents for its function. As an antioxidant enzyme, GPx1 modulates the balance between necessary and harmful levels of reactive oxygen species. In this review, we discuss how selenium availability and modifiers of selenocysteine incorporation alter GPx1 expression to promote disease states. We review the role of GPx1 in cardiovascular and metabolic health, provide examples of how GPx1 modulates stroke and provides neuroprotection, and consider how GPx1 may contribute to cancer risk. Overall, GPx1 is protective against the development and progression of many chronic diseases; however, there are some situations in which increased expression of GPx1 may promote cellular dysfunction and disease owing to its removal of essential reactive oxygen species.

Hydrogen peroxide plays a crucial role in the melanogenesis process by regulating the activity of the key melanin-forming enzyme tyrosinase, responsible for the browning of fruits, vegetables, and seafood. Therefore, a molecule with dual activities, both efficient tyrosinase inhibition and strong hydrogen peroxide degrading ability, may act as a promising antibrowning agent. Herein, we report highly efficient selone-based mushroom tyrosinase inhibitors

Pelvic venous disorder (PVD) in women is a polyetiological multifactorial disease characterized by a high prevalence (up to 80%), a high risk of infertility, and a progressive recurrent course. Morphological changes of the venous bed occur in PVD, contributing to retrograde blood flow and pelvic phlebohypertension. It is occur due to dynamic hypervolemia and hypertension long-term exposure on the venous wall. However, PVD pathogenesis analysis only from venous hemodynamic disorders position does not explain all mechanisms of the disease development and does not contribute to the treatment measures effectiveness. Currently oxidative stress reactions are considered as the most important markers of the pathological process. The aim of our work was a comparative analysis of lipid peroxidation-antioxidant defense component changes in the peripheral and regional blood flow in women with primary pelvic venous disorder depending on the disease stage. The study involved 137 women of reproductive age (mean age 37.4±9.1 years old) with diagnosed primary PVD divided into 3 groups according to the pathological process stages (stages I, II, III). Data from 30 practically healthy women (mean age 33.5±6.3 years old) were used as controls. Spectrophotometric, fluorometric, immunoassay and statistical methods were used. In patients with PVD stage I in peripheral bloodstream were higher values of SOD and GPO activity; in the regional bloodstream were higher levels of TBARs, SOD, catalase, GPO and lower GSH. In PVD stage II the peripheral bloodstream showed elevated levels of DC, GSH and SOD reduced levels; the regional bloodstream showed higher levels of DC, TBARs, GPO and GSH reduced levels relative to controls. PVD stage III was characterized by: higher levels of DC and TBARs and lower levels of SOD and GSH in the peripheral bloodstream; higher levels of DC, TBARs and lower levels of GSH and catalase in the regional bloodstream compared with control. Thus, the results of our study showed no significant differences in the LPO-AOD system between peripheral and regional bloodstreams in patients with PVD depending on the disease stage. However, negative changes in the redox balance in the regional bloodstream were earlier and were already registered at the first stage of the disease. It is likely that control of antioxidant insufficiency in patients with PVD should be an important component of preventive measures in the early stages and pathogenetic treatment in the pathological process progression, particularly in stage III of the disease.

In this study, the neuroprotective action potential by ulexite (UX) (18.75 mg/L) against acetylferrocene (AFC) (3.82 mg/L) induced neurotoxicity was aimed to investigate in brain tissues of Oncorhynchus mykiss. For this purpose, the effects on neurotoxicity markers, proinflammatory cytokines, antioxidant immune system, DNA, and apoptosis mechanisms were assessed on brain tissues in the 48-96 h of the 96- trial period. In this research, it was determined that brain-derived nerve cell growth factor (BDNF) level and acetylcholinesterase (AChE) activity were inhibited in the brain tissue compared to the control group by AFC. In addition, inhibition in glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) values (which are antioxidant system biomarkers), and inductions in malondialdehyde (MDA) and myeloperoxidase (MPO) amounts (which are indicators of lipid peroxidation) were determined (p 0.05) after exposure to AFC. And, while tumor necrosis factor-α (TNF-α) and IL-6 levels were increased in the AFC-exposed group, Nrf-2 levels were found to be remarkably decreased. Upregulation was also detected in 8-hydroxydeoxyguanosine (8-OHdG) and caspase-3 levels, which are related to DNA damage and apoptosis mechanism. On the contrary, UX (single/with AFC) suppressed the AChE and BDNF inhibition by AFC. Moreover, UX mitigated AFC-induced oxidative, inflammatory, and DNA damage and attenuated AFC-mediated neurotoxicity via activating Nrf2 signaling in fish. Collectively, our findings revealed that UX supplementation might exert beneficial effects and may be considered as a natural and promising neuroprotective agent against AFC-induced toxicity.

Metabolic syndrome, including obesity has been documented as a critical factor in male reproductive dysfunction with subsequent reduction in male fertility. The therapeutic potential of melatonin has been demonstrated against oxidative stress-induced pathologies. Therefore, the present study investigated the effects of melatonin on testicular dysfunction associated with high fat diet (FD)-induced obese rat model, and the possible involvement of peroxisome proliferator-activated receptor-γ (PPAR-γ). Adult male Wistar rats (n = 6/group) were used: control group received vehicle (normal saline), obese group received 40% FD, melatonin-treated group received melatonin (4 mg/kg), and obese plus melatonin group received melatonin and 40% FD and the treatment lasted for 12 weeks. High fat diet caused increased body weight and testicular triglyceride, total cholesterol, malondialdehyde, γ-glutamyl transferase, lactate production and lactate/pyruvate ratio as well as decreased glutathione/glutathione peroxidase, nitric oxide and PPAR-γ and circulating testosterone. Nevertheless, all these alterations were attenuated when supplemented with melatonin. Taken together, these results demonstrates that FD-induced obesity causes testicular dysfunction. In addition, the results suggest that melatonin supplementation protects against obesity-associated testicular dysfunction and this effect is accompanied by upregulation of PPAR-γ.

When ketosis occurs, supraphysiological levels of free fatty acids (FFA) can cause oxidative injury to the mammary gland and autophagy can regulate the cellular oxidative status. The aim of this study was to investigate the autophagy status of mammary tissue and its associations with oxidative stress in healthy and clinically ketotic dairy cows. Mammary tissue and blood samples were collected from healthy cows [n = 15, β-hydroxybutyrate (BHB)0.6 mM] and clinically ketotic cows (n = 15, BHB3.0 mM) at 3 to 15 (average = 7) days in milk. For in vitro study, bovine mammary epithelial cells (BMEC) isolated from healthy cows were treated with 0, 0.3, 0.6, or 1.2 mM FFA for 24 h. Furthermore, BMEC were pretreated with 100 nM rapamycin, an autophagy activator, for 4 h or 50 mM 3-methyladenine (3-MA), an autophagy inhibitor, for 1 h, followed by treatment with or without FFA (1.2 mM) for another 24 h. Oxidation indicators and autophagy-related protein abundance were measured. Compared with healthy cows, serum concentrations of FFA, BHB, and malondialdehyde were greater in clinically ketotic cows, but milk production (kg/d), milk protein (kg/d), activities of superoxide dismutase, catalase, and glutathione peroxidase were lower. Abundances of mRNA and protein of autophagy-related gene 5 (ATG5) and 7 (ATG7) were lower, but sequestosome-1 (SQSTM1, also called p62) greater in mammary tissue of clinically ketotic cows. The mRNA abundance of microtubule-associated protein 1 light chain 3 (MAP1LC3, also called LC3) and protein abundance of LC3-II were lower in mammary tissue of clinically ketotic cows. In vitro, exogenous FFA increased the content of malondialdehyde and reactive oxygen species, but decreased the activities of superoxide dismutase, catalase, and plasma glutathione peroxidase. Compared with the 0 mM FFA group, abundance of ATG5, ATG7, LC3-II was greater, but p62 was lower in the 0.6 mM FFA-treated cells. Similarly, abundance of ATG5, ATG7, and LC3-II was lower, but p62 greater in the 1.2 mM FFA-treated cells relative to 0 mM FFA group. Culture with rapamycin alleviated oxidative stress induced by 1.2 mM FFA, whereas 3-MA aggravated it. Overall, results indicated that a low concentration (0.6 mM) of FFA can induce oxidative stress and activate autophagy in BMEC. At higher concentrations of FFA (1.2 mM), autophagy is impaired and oxidative stress is aggravated. Autophagy is a mechanism for BMEC to counteract FFA-induced stress. As such, it could serve as a potential target for further development of novel strategies against oxidative stress.

The mammalian epididymis provides an optimal and antioxidative fluid microenvironment for post-testicular sperm maturation by secretion of antioxidant scavengers and removal of excessive ROS. MicroRNAs (miRNAs) are expressed in the epididymis and involved in the regulation of epididymis physiology and functions. However, whether miRNAs are involved in regulating the antioxidant capacity and oxidative damage in the epididymis is not well understood. This study was designed to investigate the role of miR-542-3p in the regulation of antioxidant capacity and oxidative damage in the epididymis of goats. Firstly, we determined the expression of miR-542-3p and glutathione peroxidase 5 (GPx5) in the epididymis of young and adult goats using RT-qPCR assay, and found that miR-542-3p and GPx5 exhibited inverse expression levels. Our results showed that the expression level of miR-542-3p in epididymis was upregulated (P 0.05) in young goats compared to adult goats, whereas the expression level of GPx5 in epididymis was downregulated (P 0.01) in young goats compared to adult goats. Next, we further investigated the roles and potential mechanisms of miR-542-3p in epididymis using goat caput epididymal epithelial cells (GCEECs) isolated from Tai-hang goats (9-month-old). Our results showed that the overexpression of miR-542-3p in GCEECs transfected with miR-542-3p mimics resulted in decreased (P 0.05) antioxidant enzyme activities of superoxide dismutase (SOD) and catalase (CAT). Similarly, the overexpression of miR-542-3p in GCEECs resulted in decreased (P 0.05) glutathione (GSH) content and total antioxidant capacity (TAOC). In addition, the overexpression of miR-542-3p in GCEECs resulted in increased (P 0.05) malonaldehyde (MDA) content. The inverse results of SOD, CAT, GSH, TAOC and MDA were observed in the down-expression of miR-542-3p in GCEECs transfected with miR-542-3p inhibitors (P 0.05). Furthermore, GPx5 was confirmed to be a validated target of miR-542-3p in GCEECs using a dual-luciferase reporter assay, and transfection of miR-542-3p mimics decreased (P 0.05) the mRNA expression and protein level of GPx5. In conclusion, our results indicated that miR-542-3p reduced antioxidant capacity and increased oxidative damage in GCEECs by targeting GPx5. The present study further understands the regulation of antioxidant capacity and epididymal-specific GPx5 secretion in caput epididymidis.

Myocardial infarction (MI) continues to be an important issue in healthcare systems worldwide, leading to high rates of morbidity and mortality. Despite ongoing efforts towards the development of preventive measures and treatments, addressing the challenges posed by MI remains difficult both in developed and developing countries. However, researchers recently investigated the potential cardioprotective effects of taraxerol utilizing an isoproterenol (ISO)-induced cardiotoxicity model among Sprague Dawley rats. Specifically, subcutaneous tissue injections consisting of 5.25 mg/kg or 8.5 mg/kg ISO were administered over two consecutive days as stimuli to induce cardiac injury. To investigate the possibility of preventing damage caused by ISO-induced cardiotoxicity by taraxerol treatment, five groups were formed: a normal control group (1% Tween 80), an ISO control group, an amlodipine group administered 5 mg/kg/day, and various doses of taraxerol. The study results showed that treatment significantly reduced cardiac marker enzymes. Additionally, pretreatment with taraxerol increased myocardial activity in SOD and GPx, leading to significant reductions in serum CK-MB levels along with MDA, TNF-α, and IL-6. Further histopathological analysis supported these observations, as treated animals had less cellular infiltration compared to untreated ones. These multifaceted findings suggest that oral administration of taraxerol could potentially protect hearts from ISO-caused damage by increasing endogenous antioxidant concentrations while decreasing pro-inflammatory cytokines.

The antioxidant potential of foods plays a vital role in counteracting oxidative stress and its consequences in the body. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) are the primary line of defence against cellular damage caused by reactive oxygen species (ROS). Glutathione is considered to be the most vital antioxidant for the body because its changes during oxidative stress increase the risk of CVD. The dietary antioxidant capacity supporting the glutathione defence system is not known. Therefore, we analysed the glutathione defence-related markers changes in the serum of CVD patients under the dietary supplementation of increased antioxidant capacity snacks. Patients were split into groups according to inclusion criteria and dietary intervention (DI) design. The serum concentration of GPx and GST (glutathione-S-transferase) was measured before and after the 6-week DI. During the DI, CVD and control (CON) subjects increased the total diet antioxidant capacity by 48% and 21%, respectively. It resulted in a significantly decreased GST (from 3.71 to 2.54 U/g Hb, p < 0.05) and an increased GPx (from 33.90 to 38.3 U/L). The results in the CON group did not reveal significant changes in GST and GPx. This study demonstrated that an increased antioxidant capacity might be associated with improving glutathione-related defence. However, the conclusion is not substantial due to the small sample used in this study.

Oxidative stress is a pathological condition that can have adverse effects on animal health, although little research has been conducted on wildlife species. In this study, blood was collected from captive Asian elephants for the assessment of five serum oxidative status markers (reactive oxygen species (ROS) concentrations; malondialdehyde, MDA; albumin; glutathione peroxidase, GPx; and catalase) in healthy (n = 137) and sick (n = 20) animals. Health problems consisted of weakness, puncture wounds, gastrointestinal distress, eye and musculoskeletal problems, and elephant endotheliotropic herpesvirus hemorrhagic disease (EEHV-HD). Fecal samples were also collected to assess glucocorticoid metabolites (fGCMs) as a measure of stress. All data were analyzed in relation to age, sex, sampling season, and their interactions using generalized linear models, and a correlation matrix was constructed. ROS and serum albumin concentrations exhibited the highest concentrations in aged elephants (>45 years). No sex differences were found for any biomarker. Interactions were observed for age groups and seasons for ROS and catalase, while GPx displayed a significant interaction between sex and season. In pairwise comparisons, significant increases in ROS and catalase were observed in summer, with higher ROS concentrations observed only in the adult female group. Lower catalase activity was exhibited in juvenile males, subadult males, adult females, and aged females compared to subadult and adult elephants (males and females) in winter and the rainy season. There was a positive association between catalase activity and fGCMs (r = 0.23, p < 0.05), and a number of red blood cell parameters were positively associated with several of these biomarkers, suggesting high oxidative and antioxidative activity covary in red cells (p < 0.05). According to health status, elephants with EEHV-HD showed the most significant changes in oxidative stress markers, with MDA, GPx, and catalase being higher and albumin being lower than in healthy elephants. This study provides an analysis of understudied health biomarkers in Asian elephants, which can be used as additional tools for assessing the health condition of this species and suggests age and season may be important factors in data interpretation.

Purpose This study aimed to evaluate the effect of the addition of dexmedetomidine to ropivacaine on oxidative stress during transversus abdominis plane (TAP) and rectus sheath (RS) blockades for patients with end-stage renal disease (ESRD) undergoing peritoneal dialysis (PD) catheter insertion. Methods Sixty patients with ESRD undergoing PD catheter insertion to receive left ultrasound-guided TAP and RS blockades were randomly divided into two groups: the dexmedetomidine plus ropivacaine group (25 mL of 0.3% ropivacaine + 1 μg/kg dexmedetomidine) and the ropivacaine group (25 mL of 0.3% ropivacaine). Primary outcomes were oxidative stress marker levels during the procedure. Results A total of 60 patients (30 patients in each group) were evaluated. Compared with the ropivacaine group, the dexmedetomidine plus ropivacaine group had significantly lower serum malondialdehyde levels (P P P Conclusion The addition of 1 μg/kg of dexmedetomidine to ropivacaine for ultrasound-guided TAP and RS blockades could inhibit oxidative stress in patients with ESRD undergoing PD catheter insertion. Trial registration This study was registered at www.chictr.org.cn on June 7, 2021 (ChiCTR2100047050).

The study aimed to investigate the influence of heme oxygenase-1 (HO-1) on rats with diabetic retinopathy (DR) through the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. 40 rats were selected and divided into Control group (n=10), diabetes mellitus (DM) group (n=10), cobalt protoporphyrin (CoPP) group (n=10) and zinc protoporphyrin (ZnPP) group (n=10) according to weight. Streptozotocin (STZ) was intraperitoneally injected to establish the DM model in DM, CoPP and ZnPP groups, and CoPP and ZnPP solution was intraperitoneally injected in CoPP and ZnPP groups, respectively. Blood was drawn to determine fasting blood glucose. The changes in the protein and messenger ribonucleic acid (mRNA) levels were evaluated via Western blotting and polymerase chain reaction (qRT-PCR), respectively. Enzyme-linked immunosorbent assay (ELISA) was performed to measure antioxidant capacity and the levels of total reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GPx). The weight of rats was notably higher in the CoPP group and lower inZnPP group than in the DM group (p0.05). After induction of DM, compared with those in the DM group, the protein expression levels of Nrf2 and pERK were considerably elevated in the CoPP group (p0.05) but declined remarkably in the ZnPP group (p0.05). The levels of total ROS and MDA were notably elevated (p0.05) in DM and ZnPP groups, with a lowered level of GPx and distinctly elevated levels of MDA and total ROS (p0.05). Moreover, the mRNA expression level of HO-1 in the retinas of rats was remarkably raised in the DM group and CoPP group (p0.05), but it declined markedly in the ZnPP group (p0.05). The red fluorescent aggregation of Nrf2 and pERK proteins was overtly less in the ZnPP group than that in the DM group (p0.05). HO-1 can affect the level of oxidative stress and intervene in retinopathy in DM rats through the Nrf2/ERK pathway.

Objectives Favism is a metabolic disease and this study aimed to compare between olive oil and almond oil to ameliorate blood parameters, liver function, blood and liver antioxidants and DNA, and liver histology in favism rats. Methods Animals were 36 male albino rats. They classified to 2 equal (normal and favism) groups. Normal group classified to 3 equal subgroups; Control, Olive oil, and Almond oil subgroups: normal rats orally administrated with 1 mL/100 g of saline, olive oil, and almond oil, respectively. Favism group was subdivided into 3 equal subgroup; favism, favism + olive oil, and favism + almond oil subgroups: favism rats orally administrated with no treatment, 1 mL/100 g olive oil, and 1 mL/100 g almond oil, respectively. All treatments were administrated orally by oral gavage once a day for 1 month. Results The hemoglobin, hematocrite, the blood cells, glucose and glucose-6-phosphate dehydrogenase, aspartate and alanine aminotransferase, total proteins, albumin, and globulin in serum were decreased in favism. The glutathione, superoxide dismutase, and glutathione peroxidase in blood and liver were decreased in favism while alkaline phosphatase and total bilirubin in serum were increased in favism. The blood and liver malondialdehyde was increased in favism. Furthermore, oral administration with both oils in favism rats restored all these parameters to be approached the control levels. Also, both oils preserved blood and liver DNA and liver histology. Conclusions Almond oil restored blood parameters, liver function, blood and liver antioxidants and DNA, and liver histology more efficiently than olive oil in favism.

Engineered iron nanoparticles are widely used in environmental remediation, yet their potential toxic effects on marine biota remain poorly elucidated. This study aimed to gain insight into the nanoscale zero-valent iron (NZVI) toxicity mechanisms for marine invertebrates. Aside from the effect on oxidative status and histopathology, the effect of NZVI on lipid metabolism in bivalves was studied for the first time. To this end, specimens of Flexopecten glaber were exposed to ascending concentrations (0.5, 1, and 1.5 mg/L) of NZVI for 96 h. Results illustrate differential patterns of iron accumulation in the gills and the digestive gland. By increasing NZVI concentrations, the total iron level tended to markedly increase in the gills and decrease in the digestive gland, reaching 132 and 37.6 μg/g DW, respectively, in the specimens exposed to 1.5 mg/L. Biochemical and cellular biomarkers highlighted that NZVI caused oxidative stress (measured as hydrogen peroxide, malondialdehyde, and advanced oxidation protein product levels) and alterations of antioxidant defense systems, including reduced glutathione, non-protein thiol, glutathione peroxidase, superoxide dismutase, and catalase. Modulation of lipid metabolism with changed fatty acid compositions (mainly an increase in the saturation and a decrease in unsaturation levels) was also observed in both gills and digestive gland. Moreover, several histological damages, including lipofuscin accumulation, infiltrative inflammations, and digestive tubule alterations, were observed in the two studied organs, providing supplementary evidence regarding the toxic effect of NZVI. This study adds to the growing body of evidence pointing to the hazardous impacts of iron NPs on aquatic ecosystems.

Hypertension is associated with vascular injury, which contributes to end-organ damage. MicroRNAs regulating mRNAs have been shown to play a role in vascular injury in hypertensive mice. We aimed to identify differentially expressed microRNAs and their mRNA targets in small arteries of hypertensive patients with/without chronic kidney disease (CKD) to shed light on the pathophysiological molecular mechanisms of vascular remodeling.Normotensive individuals and hypertensive patients with/without CKD were recruited ( n = 15-16 per group). Differentially expressed microRNAs and mRNAs were identified uniquely associated with hypertension (microRNAs: 10, mRNAs: 68) or CKD (microRNAs: 68, mRNAs: 395), and in both groups (microRNAs: 2, mRNAs: 32) with a P less than 0.05 and a fold change less than or greater than 1.3 in subcutaneous small arteries ( n = 14-15). One of the top three differentially expressed microRNAs, miR-338-3p that was down-regulated in CKD, presented the best correlation between RNA sequencing and reverse transcription-quantitative PCR (RT-qPCR, R2 = 0.328, P 0.001). Profiling of human aortic vascular cells showed that miR-338-3p was mostly expressed in endothelial cells. Two of the selected top nine up-regulated miR-338-3p predicted targets, glutathione peroxidase 3 ( GPX3 ) and protein tyrosine phosphatase receptor type S ( PTPRS ), were validated with mimics by RT-qPCR in human aortic endothelial cells ( P 0.05) and by a luciferase assay in HEK293T cells ( P 0.05).A distinct transcriptomic profile was observed in gluteal subcutaneous small arteries of hypertensive patients with CKD. Down-regulated miR-338-3p could contribute to GPX3 and PTPRS up-regulation via the canonical microRNA targeting machinery in hypertensive patients with CKD.http://links.lww.com/HJH/C27.

Contrast-induced nephropathy (CIN) is a common complication with adverse outcome after iodinated-contrast injection, yet still lacking effective medication. Heme oxygenase-1 (HO-1) has been reported to play an important role against renal injuries. Hemin, a HO-1 inducer and anti-porphyria medicine, may have a promising effect against CIN. In this study, we aim to investigate the effect of hemin on CIN model and the underlying molecular mechanisms in human proximal tubule epithelial cells (HK-2). To mimic a common condition in percutaneous coronary intervention (PCI) patients, CIN was induced by intravenous iopromide in high-fat fed diabetic rats. We found hemin, given right before iopromide, mitigated CIN with enhanced antioxidative capacity and reduced oxidative stress. HK-2 cells insulted by iopromide demonstrated decreased cell vitality and rising reactive oxygen species (ROS), which could also be inhibited by hemin. The effects of hemin involved a key molecule in ferroptosis, glutathione peroxidase (GPX4), whose down-expression by small interfering RNA (siRNA) reversed the effect of hemin on HK-2 cells. Furthermore, hemin's induction of GPX4 involved HO-1 and nuclear factor erythroid 2-related factor 2 (Nrf2). Either HO-1 or Nrf2 inhibitor prevented hemin's effect on GPX4 to a comparable extent, and over-expression of Nrf2 increased GPX4 expression. Moreover, intervention of ferroptosis inhibitor liproxstatin-1 also alleviated CIN in vivo. Therefore, we showed hemin mitigated CIN, inhibiting oxidative stress and ferroptosis, by upregulation of GPX4 via activation of HO-1/Nrf2. Hemin, as a clinical medicine, has a translational significance in treating CIN, and anti-ferroptosis is a potential therapeutic strategy for CIN.

Allergic asthma which is induced by ovalbumin (OVA) is a chronic airway inflammation disease. Isoorientin (Iso) is a natural C-glucosyl flavone with many biological properties. We aimed to evaluate the effectiveness of Iso on OVA-induced allergic asthma. A total of 30 C57BL/6 mice were randomly divided into five groups: control group, OVA group, Dex (dexamethasone, 10 mg/kg) group, low-dose Iso group (Iso-L, 25 mg/kg), and high-dose Iso group (Iso-H, 50 mg/kg). The serum and bronchoalveolar lavage fluid (BALF) were collected for biochemical parameters, the lung tissue was collected for hematoxylin-eosin (H&E) staining, immunohistochemistry (IHC), and western blot. The levels of IL-4, IL-5, IL-13, malondialdehyde (MDA), NO, and reactive oxygen species (ROS) in Iso-L and Iso-H groups were significantly lower than that in model group ( p

Melatonin is an indole hormone secreted primarily by the pineal gland that showing anti-oxidant, anti-inflammatory and anti-apoptotic capacity. It can play an important role in the pathophysiological mechanisms of various diseases. In this regard, different studies have shown that there is a relationship between Melatonin and Multiple Sclerosis (MS). MS is a chronic immune-mediated disease of the Central Nervous System. The objective of this review was to evaluate the mechanisms of action of melatonin on oxidative stress, inflammation and intestinal dysbiosis caused by MS, as well as its interaction with different hormones and factors that can influence the pathophysiology of the disease. Melatonin causes a significant increase in the levels of catalase, superoxide dismutase, glutathione peroxidase, glutathione and can counteract and inhibit the effects of the NLRP3 inflammasome, which would also be beneficial during SARS-CoV-2 infection. In addition, melatonin increases antimicrobial peptides, especially Reg3β, which could be useful in controlling the microbiota. Melatonin could exert a beneficial effect in people suffering from MS, running as a promising candidate for the treatment of this disease. However, more research in human is needed to help understand the possible interaction between melatonin and certain sex hormones, such as estrogens, to know the potential therapeutic efficacy in both men and women.

The ability of cisplatin (cis-diamminedichloroplatinum II) toxicity to induce acute kidney injury (AKI) has attracted attention and concern for a long time, but the molecular mechanism of action for cisplatin is not clear. MicroRNA-483 is involved in several diseases, such as tumorigenesis and osteoarthritis, but its renal target and potential role in AKI are unknown. In this study, we explored the pathogenic role and underlying mechanism of miR-483-5p in cisplatin-induced AKI, using transgenic mice, clinical specimen, and in vitro cell line. We found that miR-483-5p was significantly upregulated by cisplatin in a cisplatin-induced mouse model, in serum samples of patients who received cisplatin therapy, and in NRK-52E cells. Overexpression of miR-483-5p in mouse kidneys by stereotactic renal injection of lentiviruses mediated miR-483-5p or generation of conditional miR-483-overexpressing transgenic mice accentuated cisplatin-induced AKI by increasing oxidative stress, promoting apoptosis, and inhibiting autophagy of tubular cells. Furthermore, our results revealed miR-483-5p directly targeted to GPX3, overexpression of which rescued cisplatin-induced AKI by inhibiting oxidative stress and apoptosis of tubular cells, but not by regulating autophagy. Collectively, miR-483-5p is upregulated by cisplatin and exacerbates cisplatin-induced AKI via negative regulation of GPX3 and contributing oxidative stress and tubular cell apoptosis. These findings reveal a pathogenic role for miR-483-5p in cisplatin-induced AKI and suggest a novel target for the diagnosis and treatment of AKI.

The impacts of the Batts drain on two chronically exposed fish (O. niloticus and C. gariepinus) were assessed using multiple biomarkers. Concentrations of metals in water and sediments (Cu, Zn, Fe, Cd, Pb, and Al) showed significant elevations near the Batts discharges (site 2) compared to the reference site (site 1). The liver and gills of fish collected from site 2 showed marked elevations in the catalase, superoxide dismutase, glutathione peroxidase, and thiobarbituric acid reactive substance levels. In addition, significant reductions in glutathione-reduced contents were also recorded. Tissue and species-specific antioxidant responses were associated with excessive generations of reactive oxygen species, which were visualized fluorescently. Various histological alterations were observed in the gills and livers of both species. These alterations varied between compensatory responses (ex: epithelial thickening and lifting) and irreversible damage (ex: necrotic degeneration). Based on the level of lipid peroxidation and the frequency of histopathological modifications, O. niloticus demonstrated greater resistance to the same level of pollution than C. gariepinus. Using integrated biomarkers to evaluate the real impacts of untreated discharges of the Batts drain is applied for the first time on the selected fish species at the studied sites.