Decreased Superoxide Dismutase Activity Research Articles

Serum Total Superoxide Dismutase Activity as a Predictive Factor in Patients with Hepatocellular Carcinoma

Objectives: This study aimed to determine the cutoff value for diagnosis and predict mortality in hepatocellular carcinoma (HCC) based on serum total superoxide dismutase (SOD) activity. Methods: A retrospective case-control study of the SOD Model was conducted using data from a single-center dataset at Shandong Provincial Hospital Affiliated with Shandong First Medical University, China. Serum total SOD activity was analyzed in HCC patients (n = 124) and control subjects (n = 117). Receiver operating characteristic (ROC) curves were used to determine cutoff values of serum total SOD activity for HCC diagnosis. Overall survival (OS) was assessed using the Kaplan-Meier method. Results: In the model groups, the cutoff level of total SOD activity for HCC was 169.2 U/mL (sensitivity: 87.23%, specificity: 91.95%), while for HCC [alpha fetoprotein (AFP) < 20 ng/mL], it was 173.4 U/mL (sensitivity: 86.79%, specificity: 88.51%). Additionally, in the validation groups, the true positive rate, true negative rate, and accuracy rate were all above 90%. Based on the cutoff value of SOD, HCC patients were assigned to an H-SOD and L-SOD group depending on their serum total SOD activity at admission before operation. The 5-year OS rate of the H-SOD group was 75.00%, and that of the L-SOD group was 36.59% in HCC patients (P = 0.0245). With a decrease in SOD activity, serum levels of Zn (t = 3.890, P = 0.0003) and Se (t = 7.694, P < 0.0001) were also significantly decreased and positively correlated with SOD activity (both P < 0.05) in HCC patients. Conclusions: Low serum total SOD activity may also be a risk factor for HCC. The decrease of SOD activity in HCC patients was partly related to a lack of Zn and Se.

The effects of cadmium on selected oxidative stress parameters and the content of photosynthetic pigments in cucumber Cucumis sativus L.

BackgroundEnvironmental pollution by cadmium (Cd) is currently a common problem in many countries, especially in highly industrialised areas. Cd present in the soil can be absorbed by plants through the root system. AimThe aim of the present study was to investigate the effects of cadmium on the metabolic activity of cucumber plants (Cucumis sativus L.) and the accumulation and distribution of Cd in the organs of the plants. MethodsCucumber seeds (3 g) were exposed to 0.76, 1.58 or 4.17 mg Cd/L (applied as CdCl2 solutions). The activity of selected antioxidant enzymes - glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT), lipid peroxidation and the content of photosynthetic pigments were determined in 6-week-old cucumber plants. In addition, intake of Cd has been determined by flame atomic absorption spectrometry (F-AAS). ResultsThe results show that the applied cadmium concentrations affected the activity of antioxidant enzymes. An increase in CAT activity and a decrease in SOD activity were observed in all cucumber organs analysed. GSH-Px activity increased in the roots and stems. Surprisingly, GSH-Px activity decreased in the leaves. The level of lipid peroxidation was usually unchanged (the only one statistically significant change was a decrease in the concentration of malondialdehyde in the leaves which was observed after exposure to the highest Cd concentration). The applied Cd concentrations had no effect on the content of photosynthetic pigments. The highest cadmium content was found in the roots of cucumber plants. Cd tends to accumulate in the roots and a small amount was translocated to the stems and leaves, which was confirmed with the translocation factor (TF). ConclusionsThe results indicate that the range of cadmium concentrations used, corresponding to the level of environmental pollution recorded in Europe, effectively activates the antioxidant enzyme system, without intensifying lipid peroxidation or reducing the content of photosynthetic pigments.

Protective effect of oxytocin on vincristine-induced gastrointestinal dysmotility in mice.

Aims: Vincristine (VCR), an antineoplastic drug, induces peripheral neuropathy characterized by nerve damage, limiting its use and reducing the quality of life of patients. VCR causes myenteric neuron damage, inhibits gastrointestinal motility, and results in constipation or paralytic ileus in patients. Oxytocin (OT) is an endogenous neuropeptide produced by the enteric nerve system, which regulates gastrointestinal motility and exerts neuroprotective effects. This study aimed to investigate whether OT can improve VCR-induced gastrointestinal dysmotility and evaluate the underlying mechanism. Methods: Mice were injected either with saline or VCR (0.1mg/kg/d, i. p.) for 14 days, and OT (0.1mg/kg/d, i.p.) was applied 1h before each VCR injection. Gastrointestinal transit and the contractile activity of the isolated colonic segments were assessed. The concentration of OT in plasma was measured using ELISA. Immunofluorescence staining was performed to analyze myenteric neurons and reactive oxygen species (ROS) levels. Furthermore, the indicators of oxidative stress were detected. The protein expressions of Nrf2, ERK1/2, P-ERK1/2, p38, and P-p38 in the colon were tested using Western blot. Results: VCR reduced gastrointestinal transit and the responses of isolated colonic segments to electrical field stimulation and decreased the amount of neurons. Furthermore, VCR reduced neuronal nitric oxide synthase and choline acetyltransferase immunopositive neurons in the colonic myenteric nerve plexus. VCR increased the concentration of OT in plasma. Exogenous OT pretreatment ameliorated the inhibition of gastrointestinal motility and the injury of myenteric neurons caused by VCR. OT pretreatment also prevented the decrease of superoxide dismutase activity, glutathione content, total antioxidative capacity, and Nrf2 expression, the increase of ROS levels, and the phosphorylation of ERK1/2 and p38 MAPK following VCR treatment. Conclusion: Our results suggest that OT pretreatment can protect enteric neurons from VCR-induced injury by inhibiting oxidative stress and MAPK pathways (ERK1/2, p38). This may be the underlying mechanism by which it alleviates gastrointestinal dysmotility.

Effect of light and noise pollution on oxidative stress and proximate composition in Dreissena polymorpha

In this study, it was aimed to determine the effect of sound and light pollution on Zebra mussel (Dreissena polymorpha) by biomarker and nutritional composition. For this purpose, an experimental design was carried out in laboratory conditions where the model was exposed to live sound, light, and combined sound + light parameters for 30 min every hour over 96 h. Changes in the biomarkers superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, as well as glutathione (GSH) and thiobarbituric acid (TBARS) levels, were assessed in the model organism exposed to sound, light, and sound + light pollution. The changes in protein and fat amounts were determined. When the changes in biomarkers were examined statistically compared to the control, there was no significant decrease in SOD activity (p < 0.05), a significant increase in CAT activity in sound and sound+light, but a significant decrease in light (p < 0.05), no significant difference in GPx activity (p > 0.05). It was determined that there was a significant increase in GSH and TBARS levels in all three parameters. Significant changes were also observed in the proximate composition. As a result, exposure to sound, light and sound+light pollution caused an increase in oxidative damage and decreases in protein and lipid composition were detected.

Aristolochic acid induces acute kidney injury through ferroptosis.

Aristolochic acid (AA)-induced acute kidney injury (AKI) presents with progressive decline in renal function and rapid progression to end-stage renal disease. Among the multiple mechanisms identified in AKI, ferroptosis has been shown to be involved in various forms of AKI. But few studies have elucidated the role of ferroptosis in AA-induced AKI. In this study, we investigated the role of ferroptosis in AA-induced acute renal tubular injury in vivo and in vitro. Mice with acute aristolochic acid nephropathy showed increased malondialdehyde levels, aggravated lipid peroxidation, decreased superoxide dismutase activity, and glutathione depletion. The expression of glutathione peroxidase 4 was decreased and the expression of acyl-CoA synthetase long-chain family member 4 was increased. Inhibition of ferroptosis by ferrostatin-1 significantly improved the renal function, reduced histopathological lesions, partially alleviated lipid peroxidation, and restored the antioxidant capacity. In vitro studies also revealed that AA significantly reduced cell viability, induced reactive oxygen species production, increased intracellular iron level and decreased ferroptosis-related protein expression. Inhibition of ferroptosis significantly increased cell viability and attenuated AA-induced renal tubular epithelial cell injury. It is suggested that ferroptosis plays an important role in AA-induced acute tubular injury. And inhibition of ferroptosis may exert renoprotective effects possibly by preventing lipid peroxidation, restoring the antioxidant activity or regulating iron metabolism.

Nesfatin-1 alleviates hyperoxia-induced bronchopulmonary dysplasia (BPD) via the nuclear factor-κB (NF-κB) p65 signaling pathway.

Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease in newborns, which severely influences the health of infants and lacks effective clinical treatment strategies. The pathogenesis of BPD is correlated to enhanced inflammation and activated oxidative stress (OS). The application of antioxidants and anti-inflammatory treatment could be hot spots for BPD treatment. Nesfatin-1, a peptide with a suppressive property against inflammation, was tested herein for its potential therapeutic value in BPD. Neonatal SD rats were stimulated with hyperoxia, followed by being intraperitoneally administered with 20 μg/kg/day Nesfatin-1 for 2 weeks. Decreased RAC value in lung tissues, increased wet weight/dry weight (W/D) pulmonary ratio and bronchoalveolar lavage fluid (BALF) proteins, elevated cytokine release in BALF, increased malondialdehyde (MDA) content, and declined superoxide dismutase (SOD) activity were observed in BPD rats, all of which were sharply mitigated by Nesfatin-1. Rat epithelial type II cells (AECIIs) were handled with hyperoxia, and then cultured with 1 and 10 nM Nesfatin-1. Reduced cell viability, elevated lactate dehydrogenase production, elevated cytokine secretion, elevated MDA content, and decreased SOD activity were observed in hyperoxia-handled AECIIs, all of which were markedly alleviated by Nesfatin-1. Furthermore, activated nuclear factor-κB (NF-κB) signaling observed in both BPD rats and hyperoxia-handled AECIIs were notably repressed by Nesfatin-1. Collectively, Nesfatin-1 alleviated hyperoxia-triggered BPD by repressing inflammation and OS via the NF-κB signaling pathway.

Diazoxide attenuates DOX-induced cardiotoxicity in cultured rat myocytes.

Doxorubicin (DOX)-induced cardiotoxicity is a well known clinical problem, and many investigations have been made of its possible amelioration. We have investigated whether diazoxide (DIA), an agonist at mitochondrial ATP-sensitive potassium channels (mitoKATP), could reverse DOX-induced apoptotic myocardial cell loss, in cultured rat cardiomyocytes. The role of certain proteins in this pathway was also studied. The rat cardiomyocyte cell line (H9c2) was treated with DOX, and also co-treated with DOX and DIA, for 24 h. Distribution of actin filaments, mitochondrial membrane potential, superoxide dismutase (SOD) activity, total oxidant and antioxidant status (TOS and TAS, respectively), and some protein expressions, were assessed. DOX significantly decreased SOD activity, increased ERK1/2 protein levels, and depolarised the mitochondrial membrane, while DIA co-treatment inhibited such changes. DIA co-treatment ameliorated DOX-induced cytoskeletal changes via F-actin distribution and mitoKATP structure. Co-treatment also decreased ERK1/2 and cytochrome c protein levels. Cardiomyocyte loss due to oxidative stress-mediated apoptosis is a key event in DOX-induced cytotoxicity. DIA had protective effects on DOX-induced cardiotoxicity, via mitoKATP integrity, especially with elevated SUR2A levels; but also by a cascade including SOD/AMPK/ERK1/2. Therefore, DIA may be considered a candidate agent for protecting cardiomyocytes against DOX chemotherapy.

Peculiarities of changes in a functional condition of pro-oxidant and antioxidant systems in guinea pigs’ lungs in experimental allergic alveolitis under the conditions of immobilization stress

We have analyzed the results of investigation of alterations in indices of pro-oxidant (conjugated diene and malondialdehyde) and antioxidant (superoxide dismutase, ceruloplasmin, catalase) systems in guinea pigs’ lungs in experimental allergic alveolitis in the dynamics of EAA development under the conditions of immobilization stress. The investigation was conducted on 62 female guinea pigs weighing 180-220 g, divided into 4 groups: I – intact guinea pigs (n=20), II – guinea pigs (n=14) with EAA under the conditions of IS (1st day); III – guinea pigs (n=14) with EAA under the conditions of IS (2nd day); IV – guinea pigs (n=14) with EAA under the conditions of IS (34th day). The results of experimental investigation showed that a significant increase in conjugated diene level in animals’ lungs was observed at all stages of EAA development under the conditions of immobilization stress as compared with control group, indicating activation of this marker. The same changes occurred with MDA content, indicating excessive accumulation of this lipid peroxidation product in lung tissue. Intensive synthesis of free radical compounds caused activation of some components of enzymatic system of antioxidant defense. In particular, a moderate decrease in superoxide dismutase activity in lung tissue is observed in response to increased level of LOPs at early stages of EAA and immobilization stress development as compared with the indices in intact animals. The same situation is observed with catalase and ceruloplasmin activity in the lungs of guinea pigs with modeled AA and IS.

Exposure to nanopolystyrene and phoxim at ambient concentrations causes oxidative stress and inflammation in the intestines of the Chinese mitten crab (Eriocheir sinensis)

Nanopolystyrene (NP) and phoxim (PHO) are common environmental pollutants in aquatic systems. We evaluated the toxic effects of exposure to ambient concentrations of NP and/or PHO in the intestines of the Chinese mitten crab (Eriocheir sinensis). Our study showed that histopathological changes were observed in the intestines. Specifically, NP and/or PHO exposure increased intraepithelial lymphocytes. Furthermore, NP and/or PHO exposure induced oxidative stress, as evidenced by a significant decrease in superoxide dismutase activity (SOD), peroxidase activity (POD), and total antioxidant capacity (T-AOC). Pro-inflammatory gene expression and transcriptome analysis demonstrated that NP and/or PHO exposure induced the intestinal inflammatory response. Transcriptome results showed that NP and/or PHO exposure upregulated the NF-κB signaling pathway, which is considered a key pathway in the inflammatory response. Additionally, the expression of pro-inflammatory genes significantly increased after a single exposure to NP or PHO, but it exhibited a significant decrease after the co-exposure. The downregulation of these genes in the co-exposure group likely suggested that the co-exposure mitigated intestinal inflammation response in E. sinensis. Collectively, our findings mainly showed that NP and/or PHO exposure at ambient concentrations induces oxidative stress and inflammatory response in the intestines of E. sinensis.

Neuroprotective Effect of Resveratrol against Manganese-Induced Oxidative Stress and Matrix Metalloproteinase-9 in an "In Vivo" Model of Neurotoxicity.

Chronic exposure to manganese (Mn) leads to its accumulation in the central nervous system (CNS) and neurotoxicity with not well-known mechanisms. We investigated the involvement of matrix metalloproteinase (MMP)-2 and -9 in Mn neurotoxicity in an in vivo model of rats treated through an intraperitoneal injection, for 4 weeks, with 50 mg/kg of MnCl2 in the presence or in the absence of 30 mg/kg of resveratrol (RSV). A loss of weight was observed in Mn-treated rats compared with untreated and RSV-treated rats. A progressive recovery of body weight was detected in rats co-treated with Mn and RSV. The analysis of brain homogenates indicated that RSV counteracted the Mn-induced increase in MMP-9 levels and reactive oxygen species production as well as the Mn-induced decrease in superoxide dismutase activity and glutathione content. In conclusion, Mn exposure, resulting in MMP-9 induction with mechanisms related to oxidative stress, represents a risk factor for the development of CNS diseases.

Induction of Oxidative Stress by Waterborne Copper and Arsenic in Larvae of European Seabass (Dicentrarchus labrax L.): A Comparison with Their Effects as Nanoparticles.

The aim of this work was to compare the potential induction of oxidative stress and the antioxidant enzymatic response after a short-term waterborne exposure to copper (Cu) and arsenic (As) with that of the nanoparticles (NPs) of these elements (Cu-NPs and As-NPs) in fish larvae of the species Dicentrarchus labrax. Larvae were grouped in several tanks and exposed to different concentrations of contaminants (0 to 10 mg/L) for 24 or 96 h under laboratory conditions. Copper and arsenic concentrations were analysed in larval tissues using ICP-MS. A set of oxidative stress biomarkers, including the levels of hydroperoxides (HPs), and superoxide dismutase (SOD) and catalase (CAT) activities were assessed. The trace element concentrations (mg/kg d.w.) in larvae ranged as follows: 3.28-6.67 (Cu at 24 h) and 2.76-3.42 (Cu at 96 h); 3.03-8.31 (Cu-NPs at 24 h) and 2.50-4.86 (Cu-NPs at 96 h); 1.92-3.45 (As at 24 h) and 2.22-4.71 (As at 96 h); and 2.19-8.56 (As-NPs at 24 h) and 1.75-9.90 (As-NPs at 96 h). In Cu tests, the oxidative damage (ROOH levels) was induced from 0.1 mg/L at both exposure times, while for Cu-NPs, this damage was not observed until 1 mg/L, which was paralleled by concomitant increases in SOD activity. The CAT activity was also increased but at lower metal concentrations (0.01 mg/L and 0.1 mg/L for both chemical forms). No oxidative damage was observed for As or As-NPs after 24 h, but it was observed for As after 96 h of treatment with 0.01 mg/L. A decrease in SOD activity was observed for As after 24 h, but it turned out to be increased after 96 h. However, As-NPs did not alter SOD activity. The CAT activity was stimulated only at 96 h by As and at 24 h by As-NPs. Therefore, the two chemical forms of Cu exhibited a higher bioaccumulation and toxicity potential as compared to those of As. Importantly, the association of both Cu and As in NPs reduced the respective trace metal bioaccumulation, resulting also in a reduction in the toxic effects (mortality and biochemical). Furthermore, the assessment of oxidative stress-related biomarkers in seabass larvae appears to be a useful tool for biomonitoring environmental-occurring trace elements.

Tanshinone IIA regulates CCl4 induced liver fibrosis in C57BL/6J mice via the PI3K/Akt and Nrf2/HO-1 signaling pathways.

Chronic liver diseases caused by various factors may develop into liver fibrosis (LF). Early stage of LF could be reversible. Tanshinone IIA (Tan IIA), an extract from Salvia miltiorrhiza, has been reported to be hepatoprotective. However, the potential targets and mechanism of Tan IIA in the treatment of LF are still unclear. Our study aims at the anti-LF mechanism of Tan IIA through network pharmacological analysis combined with LF-related experiments. Serum biochemical indicators and histopathological examination showed that Tan IIA could ameliorate the process of LF in the CCl4 -induced mouse model. Western blot and immunohistochemical assays showed that Tan IIA decreased the expression of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositide 3-kinases/protein kinase B (PI3K/Akt), and nuclear factor erythroid 2-related factor/heme oxygenase-1 (Nrf2/HO-1). Compared with the model group, the Tan IIA groups increased the decreased superoxide dismutase activity and glutathione content, while decreasing the increased malondialdehyde content. These results indicate that Tan IIA may play an antioxidant role by inhibiting the expression of KRAS, PI3K/Akt, and Nrf2/HO-1 to ameliorate the progression of LF, which to some extent explains the pharmacological mechanism of Tan IIA in LF. In conclusion, our study demonstrates that Tan IIA could regulate LF via PI3K/Akt and Nrf2/HO-1 signaling pathways. It may be an effective therapeutic compound for the treatment of LF.

Resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by maintaining mitochondrial homeostasis via enhancing SIRT1 expression

To investigate whether resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by enhancing the expression of silent information regulation 2 homolog 1 (SIRT1) to maintain mitochondrial homeostasis. Rat cardiomyocytes H9c2 cells with or without lentivirus-mediated mRNA interference of SIRT1 were cultured in high glucose (HG) and treated with resveratrol for 72 h. The changes in superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, reactive oxygen species (ROS) level, and relative surface of the cells were examined, and the mRNA expressions of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) and protein expressions of SIRT1, mitochondrial fusion related proteins optic atrophy protein 1 (OPA1) and mitofusin 2, mitochondrial division related proteins dynamin-related protein 1 (DRP1) and fission protein 1 (FIS1), and mitophagy-related proteins BNIP3L and LC3 were detected using RT-qPCR and Western blotting. HG exposure significantly decreased SOD activity, increased MDA content, ROS production, relative cell surface, and the mRNA expressions of ANF and BNP in the cardiomyocytes; the protein expressions of SIRT1, OPA1, mitofusin 2 and BNIP3L and LC3-Ⅱ/LC3-Ⅰ ratio were all decreased and the protein expressions of DRP1 and FIS1 increased in HG-exposed cells (P<0.01). All these changes in HG-exposed cardiomyocytes were significantly alleviated by treatment with resveratrol (P<0.05). The protective effects of resveratrol against HG exposure in the cardiomyocytes were obviously attenuated by transfection of the cells with si-SIRT1 (P<0.05). Resveratrol inhibits hyperglycemia-induced cardiomyocyte hypertrophy by reducing oxidative stress, the mechanisms of which involve enhancement of SIRT1 protein expression, regulation of mitochondrial fusion and division balance, and promoting BNIP3L-mediated mitophagy to maintain mitochondrial homeostasis in the cells.

Effects of polyethylene microplastics stress on soil physicochemical properties mediated by earthworm Eisenia fetida.

Microplastics (MPs) are widely distributed in soil environments, but their ecological risks are not fully understood. To fill this knowledge gap, incubation experiments were conducted to explore the physiological response of Eisenia foetida (E. fetida) to polyethylene MP stress and its effects on soil physicochemical properties. E. fetida was incubated in soils amended with MPs of two particle sizes (13μm and 130μm) at six concentrations (0, 1, 3, 6, 10 and 20g MPs·kg-1 soil) under laboratory conditions. The toxicity of 13μm MPs on the growth and survival of E. fetida was greater than that of 130μm MPs. Excessive reactive oxygen species accumulation induced by high MP concentrations decreased superoxide dismutase activity and increased malondialdehyde content. Soil pH increased significantly in the 130μm treatments. MPs increased the contents of soil organic carbon and available potassium. However, the presence of MPs did not significantly alter available phosphorus or nitrate nitrogen content. MP contamination in soil may have adverse impacts on the growth of earthworms, induce oxidative stress in earthworms, and change soil physicochemical properties. In addition, the effects of MPs are size-dependent and dose-dependent. This study provides new evidence for the ecological risks of MP pollution in the earthworm-soil systems.

Ivermectin ameliorates bleomycin-induced lung fibrosis in male rats by inhibiting the inflammation and oxidative stress

Background Idiopathic pulmonary fibrosis (IPF) is a pulmonary fibrotic disease characterized by a poor prognosis, which its pathogenesis involves the accumulation of abnormal fibrous tissue, inflammation, and oxidative stress. Ivermectin, a positive allosteric modulator of GABAA receptor, exerts anti-inflammatory and antioxidant properties in preclinical studies. The present study investigates the potential protective effects of ivermectin treatment in rats against bleomycin-induced IPF. Materials and Methods The present study involved 42 male Wistar rats, which were divided into five groups: control (without induction of IPF), bleomycin (IPF-induced by bleomycin 2.5 mg/kg, by intratracheal administration), and three fibrosis groups receiving ivermectin (0.5, 1, and 3 mg/kg). lung tissues were harvested for measurement of oxidative stress [via myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione (GSH)] and inflammatory markers (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], and transforming growth factor-β [TGF-β]). Histological assessments of tissue damage were performed using hematoxylin–eosin (H&E) and Masson’s trichrome staining methods. Results The induction of fibrosis via bleomycin was found to increase levels of MPO as well as TNF-α, IL-1β, and TGF-β while decrease SOD activity and GSH level. Treatment with ivermectin at a dosage of 3 mg/kg was able to reverse the effects of bleomycin-induced fibrosis on these markers. In addition, results from H&E and Masson’s trichrome staining showed that ivermectin treatment at this same dose reduced tissue damage and pulmonary fibrosis. Conclusion The data obtained from this study indicate that ivermectin may have therapeutic benefits for IPF, likely due to its ability to reduce inflammation and mitigate oxidative stress-induced toxicity.

Does Nanosilver Exposure Modulate Steroid Metabolism in the Testes?-A Possible Role of Redox Balance Disruption.

Silver nanoparticles (AgNPs) are a popular engineered nanomaterial widely used in industry. Despite the benefits they bring to society, AgNPs are not neutral to human health. The aim of this study was to evaluate the effects of a single intravenous dose (5 mg/kg body weight) of 20 nm AgNPs on steroid metabolism and redox balance in the testes of adult rats. The effects were evaluated 1 day or 28 days after intervention and compared with saline-treated animals. Decreased aromatase and estrogen receptor α levels (by 21% and 27%, respectively) were observed 1 day after AgNPs administration, while increased testosterone, increased dihydrotestosterone levels, higher androgen receptors and higher aromatase expression in Leydig cells (by 43%, 50%, 20% and 32%, respectively) as well as lower (by 35%) androgen receptor protein levels were observed 28 days after exposure to AgNPs compared to control groups. The AgNPs treatment resulted in decreased superoxide dismutase activity, decreased GSH/GSSG ratio, and increased glutathione reductase activity (by 23%, 63% and 28%, respectively) compared to control animals, irrespective of the time of measurement. Increased (by 28%) intratesticular lipid hydroperoxides level was observed 1 day after AgNPs exposure, while decreased (by 70%) GSH and increased (by 43%) 7-ketocholesterol levels were observed 28 days after treatment compared to control animals. Conclusions: AgNPs exposure caused redox imbalance in the gonads shortly after AgNPs administration, while a longer perspective AgNPs exposure was associated with impaired androgen metabolism, probably due to increased oxidative stress.

Dietary supplementation with green tea extract improves the antioxidant status and oocyte developmental competence in Italian Mediterranean buffaloes

The aim of this work was to assess the antioxidant status and the developmental competence of oocytes recovered by ovum pick-up (OPU) in Italian Mediterranean buffaloes supplemented with green tea extracts (GTE) for 90 days. Buffalo cows (n = 16) were randomly assigned to a control group receiving no supplement and a treatment group, receiving GTE starting 90 days before OPU, carried out for five consecutive sessions. Blood samples were collected before the start of supplementation with GTE (T0) and at day 45 (T1) and day 90 (T2) of supplementation, to measure ferric reducing activity (FRAP), total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT). The antioxidant status of follicles was measured as TAC on the follicular fluid collected from the dominant follicle just prior OPU, coinciding with T2, and at the end of five repeated OPU sessions (T3). Another objective was to assess in vitro the protective effects of green tea extracts on hepatic cells exposed to methanol insult. Different concentrations of GTE (0.5 μM and 1 μM) were tested on cultured hepatic cells and viability, morphology and SOD activity were assessed at 24, 48 and 72 h.Supplementation with GTE increased (P < 0.05) the number of total follicles (8.7 ± 0.5 vs 6.9 ± 0.5), the number and the percentage of Grade A + B cumulus-oocyte complexes (COCs) compared with the control (3.7 ± 0.4 vs 2.3 ± 0.3 and 57.5 ± 4.2 vs 40.4 ± 4.9 %, respectively). Oocyte developmental competence was improved in the GTE group as indicated by the higher (P < 0.05) percentages of Grade 1,2 blastocysts (44.8 vs 29.1 %). In the GTE group, plasma TAC was higher both at T1 and T2, while FRAP increased only at T2, with no differences in SOD and CAT. The TAC of follicular fluid was higher (P < 0.05) in the GTE compared to the control both at T2 and at T3 The in vitro experiment showed that co-treatment with methanol and 1 μM GTE increased (p < 0.01) cell viability at 24 h (P < 0.01), 48 h (P < 0.05) and 72 h (P < 0.01) compared with the methanol treatment co-treatment with 1 μM GTE prevented the decrease in SOD activity observed with methanol at 24 and 48 h of culture. In conclusion, the results of in vivo and in vitro experiments suggest that supplementation with GTE increases buffalo oocyte developmental competence, by improving oxidative status and liver function.

Hederagenin Upregulates PTPN1 Expression in Aβ-Stimulated Neuronal Cells, Exerting Anti-Oxidative Stress and Anti-Apoptotic Activities.

Alzheimer's disease (AD) is a prevalently neurodegenerative disease characterized by neuronal damage which is associated with amyloid-β (Aβ) accumulation. Hederagenin is a triterpenoid saponin, exerting anti-apoptotic, anti-oxidative, anti-inflammatory, anti-tumoral, and neuroprotective activities. However, its role in AD progression is still obscure. The aim of this study was to explore the influences of hederagenin on Aβ-caused neuronal injury in vitro. Neuronal cells were treated with Aβ25-35 (Aβ) to establish a cellular model of AD. Cell viability was assessed using cell counting kit-8 (CCK-8). Oxidative stress was evaluated by detecting reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity. Apoptosis was investigated using TUNEL staining and caspase-3 activity assays. Protein tyrosine phosphatase nonreceptor type 1 (PTPN1) was screened by bioinformatics analysis. Protein levels of PTPN1 and protein kinase B (Akt) were measured by western blotting. Hederagenin (2.5, 5, and 10μM) alone did not affect viability of neuronal cells, but relieved Aβ-induced viability reduction. Hederagenin mitigated Aβ-induced increase in ROS accumulation and decrease in SOD activity. Hederagenin attenuated Aβ-induced increase in apoptotic rate and caspase-3 activity. PTPN1 was screened as a target of hederagenin against AD by bioinformatics analysis. Hederagenin treatment resisted Aβ-induced decrease in PTPN1 mRNA and protein levels in neuronal cells. PTPN1 silencing attenuated the suppressive functions of hederagenin in Aβ-stimulated oxidative stress and apoptosis. Hederagenin mitigated Aβ-induced Akt signaling inactivation by upregulating PTPN1 expression. In conclusion, hederagenin attenuates oxidative stress and apoptosis in neuronal cells stimulated with Aβ by promoting PTPN1/Akt signaling activation.

A2BR facilitates the pathogenesis of H. pylori-associated GU by inducing oxidative stress through p38 MAPK phosphorylation

Gastric ulcers significantly impact the quality of life of patients, the pathogenesis of which is closely associated with Helicobacter pylori (HP) infection. Oxidative stress is involved in the pathological mechanism of gastric ulcers. Recently, adenosine A2B Receptor (A2BR) was reported to activate the p38MAPK pathway. However, the role of A2BR in gastric ulcers remains unknown. In the present study, the biological function of A2BR in HP-induced gastric ulcers was investigated to explore novel targets for gastric ulcers. GES-1 cells were infected with HP, followed by incubation with 10 μM BAY60-6583 (A2BR agonist) and 25 nM PSB1115 (A2BR antagonist). In HP-infected GES-1 cells, an increased apoptotic rate, enhanced migration ability, excessive release of reactive oxygen species (ROS), increased malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity were observed, accompanied by the activation of p38MAPK signaling, which were dramatically aggravated by BAY60-6583 and alleviated by PSB1115. In animal experiments, rats were treated with 2 mg/kg BAY60-6583 and 10 mg/kg PSB1115, followed by gastric ulcer modeling 30 min later. In HP-infected rats, increased ulcer area, elevated pepsin activity, increased hematoxylin and eosin (HE) pathological scores, increased MDA levels, and decreased SOD activity were observed, which were further aggravated by BAY60-6583 and ameliorated by PSB1115. Finally, the effects of A2BR activation on apoptosis, migration, oxidative stress, and p38MAPK signaling in HP-infected GES-1 cells were reversed by an inhibitor of the p38MAPK pathway. Collectively, A2BR facilitated the pathogenesis of HP-induced gastric ulcers by inducing oxidative stress through p38MAPK activation.

The state of lipid metabolism indicators and the system of peroxidation — antioxidant protection in aluminum production workers with occupational bronchopulmonary pathology

Introduction. In aluminum production workers, the most common occupational pathology is bronchopulmonary diseases, which are characterized by the formation of comorbid pathologies. Oxidative stress plays a key role in the pathogenesis of bronchopulmonary and cardiovascular pathologies.&#x0D; The study aims to research the indicators of oxidative metabolism and antioxidant protection in aluminum production workers with occupational bronchopulmonary pathology (OBPP) during work and post-contact period.&#x0D; Materials and methods. During the study, on the basis of the therapeutic department of the clinic at East-Siberian Institute of Medical and Ecological Research, scientists examined 130 patients — workers of aluminum production, with an established professional diagnosis of the bronchopulmonary system both during work and in the post-contact period. The authors have analyzed the indicators of oxidative stress, lipid metabolism and the concentration of antibodies to oxidized low-density lipoproteins.&#x0D; Results. In patients with OBPP, decreased superoxide dismutase activity was more common during work than in the post-exposure period. About 60% of the examined patients had elevated cholesterol levels, almost 40% had higher reference values of the atherogenicity index and the content of antibodies to oxidized low-density lipoproteins. Cholesterol levels in high-density lipoproteins in individuals with OBPP in the long-term period were lower than in individuals with the same pathology during the work period.&#x0D; Conclusion. The depletion of antioxidant protection in workers in the post-contact period of the OBPP, the researchers noted in the form of a decrease in the activity of superoxide dismutase in every third person examined, which can lead to the formation of endothelial dysfunction. An increase in the fractions of atherogenic cholesterol is accompanied by a significant increase in the occurrence of a reduced level of high-density lipoprotein cholesterol, which has anti-atherogenic properties.&#x0D; Ethics. The examination of patients met ethical standards in accordance with the Helsinki Declaration of the World Association "Ethical Principles of Conducting Scientific Medical Research with Human Participation", as amended in 2000 and the "Rules of Clinical Practice in the Russian Federation", approved by Order of the Ministry of Health of the Russian Federation No. 266 of 06/19/2003. All the surveyed signed an informed consent to participate in the study. The protocol of the study was approved by the Ethics Committee of the East Siberian Institute of Medical and Environmental Research (Protocol No. 6 of 10.03.2020).