Decreased Superoxide Dismutase Activity Research Articles

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.

Polyethylene microplastics affect behavioural, oxidative stress, and molecular responses in the Drosophila model.

The escalating presence of microplastic pollution poses a significant environmental threat, with far-reaching implications for both ecosystems and human health. This study investigated the toxicological impact of polyethylene microplastics (PE MPs) using Drosophila melanogaster, fruit flies, as a model organism. Drosophila were exposed to PE MPs orally at concentrations of 1 mg ml-1 and 10 mg ml-1 agar food. The study assessed behavioural parameters and biochemical markers including reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione-S-transferase (GST) activity. The expression levels of key genes (Hsp70Bc, rpr, and p53) were also analysed using the RT-qPCR technique. Results indicated a significant decline in climbing activity among adult flies and crawling behaviour in larvae, indicating potential disruption of motor function. Biochemical analysis revealed elevated ROS levels, indicative of oxidative stress, in both larval and fly stages. Moreover, the antioxidant defence system exhibited decreased SOD activity and a concentration-dependent increase in GST activity indicating the functioning of a quick xenobiotic clearance mechanism. Gene expression analysis demonstrated upregulation of rpr, p53, and Hsp70Bc genes, suggesting activation of cell death pathways and stress response mechanisms. Overall, these findings underline the adverse effects of PE MPs on Drosophila, including behavioural impairment, oxidative stress, and activation of stress response pathways.

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).

Gossypin mitigates oxidative damage by downregulating the molecular signaling pathway in oleic acid-induced acute lung injury.

One of the leading causes of acute lung injury, which is linked to a high death rate, is pulmonary fat embolism. Increases in proinflammatory cytokines and the production of free radicals are related to the pathophysiology of acute lung injury. Antioxidants that scavenge free radicals play a protective role against acute lung injury. Gossypin has been proven to have antioxidant, antimicrobial, and anti-inflammatory properties. In this study, we compared the role of Gossypin with the therapeutically used drug Dexamethasone in the acute lung injury model caused by oleic acid in rats. Thirty rats were divided into five groups; Sham, Oleic acid model, Oleic acid+Dexamethasone (0.1 mg/kg), Oleic acid+Gossypin (10 and 20 mg/kg). Two hours after pretreatment with Dexamethasone or Gossypin, the acute lung injury model was created by injecting 1 g/kg oleic acid into the femoral vein. Three hours following the oleic acid injection, rats were decapitated. Lung tissues were extracted for histological, immunohistochemical, biochemical, PCR, and SEM imaging assessment. The oleic acid injection caused an increase in lipid peroxidation and catalase activity, pathological changes in lung tissue, decreased superoxide dismutase activity, and glutathione level, and increased TNF-α, IL-1β, IL-6, and IL-8 expression. However, these changes were attenuated after treatment with Gossypin and Dexamethasone. By reducing the expression of proinflammatory cytokines and attenuating oxidative stress, Gossypin pretreatment provides a new target that is equally effective as dexamethasone in the treatment of oleic acid-induced acute lung injury.

Polysaccharides from Polygonatum cyrtonema Hua prevent post-traumatic stress disorder behaviors in mice: Mechanisms from the perspective of synaptic injury, oxidative stress, and neuroinflammation

Ethnopharmacological relevanceAccording to traditional Chinese medicine (TCM) theory, post-traumatic stress disorder (PTSD) is a kind of depression syndrome, and its occurrence is related to deficiencies of the heart and kidney. Polygonatum cyrtonema Hua replenishes Qi and blood and tonifies the five zang organs, so it is widely used in TCM as a prescription for the treatment of depression syndrome. The polysaccharides in P. cyrtonema Hua (PSP) are the main active components of the herb, but the effects of PSP on PTSD and the mechanisms remain unclear. Aim of the studyTo investigate the preventive effect of PSP on PTSD-like behaviors and to determine the mechanisms. MethodsWe used behavioral tests to evaluate PTSD-like behaviors in mice. Synaptic changes were assessed by transmission electron microscopy. Hematoxylin-eosin staining was used to assess pathological changes to the hippocampus, and immunofluorescence staining was used to observe changes in astrocytes. Serum corticosterone (CORT), cytokine, and hippocampal oxidation-related indicator levels were evaluated by ELISA. We detected the expression levels of synaptic, oxidative, and inflammation-related proteins in the hippocampus by western blotting. ResultsSingle prolonged stress (SPS)-modeled mice exhibited significant PTSD-like phenotypes, including increased fear memory acquisition and anxiety-like behaviors. These behavioral changes were prevented by PSP administration. Compared to controls, SPS modeling increased serum CORT, cytokine, and hippocampal malondialdehyde levels; decreased superoxide dismutase activity; and caused losses in pyramidal neurons, astrocytes, and synapses in the CA1 region. At the molecular level, the expression of brain-derived neurotrophic factor, postsynaptic density protein 95, nuclear factor erythroid 2-related factor 2 (Nrf2), phospho-tyrosine kinase receptor B, activity-regulated cytoskeleton-associated protein, heme oxygenase-1 (HO-1), and GluA1 decreased in SPS mice compared with the control group, while the expression of NOD-like receptor protein 3 (NLRP3), GluN2B, and apoptosis-associated speck-like protein increased in SPS mice. Treatment with PSP counteracted these abnormal changes. Importantly, ML385, an Nrf2 inhibitor, blocked PSP's ability to ameliorate PTSD behaviors and abnormal protein expression. The NLRP3 inhibitor MCC950 reduced the PTSD-like behaviors and normalized protein expression in SPS mice. ConclusionPSP prevents SPS-induced PTSD-like behaviors and synaptic damage by regulating oxidative stress and NLRP3-mediated inflammation, probably in an Nrf2/HO-1 signaling pathway-dependent manner.

Integration of systematic review, lipidomics with experiment verification reveals abnormal sphingolipids facilitate diabetic retinopathy by inducing oxidative stress on RMECs

ObjectiveThis study aims to explore the potential biomarkers in the development of diabetes mellitus (DM) into diabetic retinopathy (DR). MethodsSystematic review of diabetic metabolomics was used to screen the differential metabolites and related pathways during the development of DM. Non-targeted lipidomics of rat plasma was performed to explore the differential metabolites in the development of DM into DR in vivo. To verify the effects of differential metabolites in inducing retinal microvascular endothelial cells (RMECs) injury by increasing oxidative stress, high glucose medium containing differential metabolites was used to induce rat RMECs injury and cell viability, malondialdehyde (MDA) contents, superoxide dismutase (SOD) activities, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated in vitro. Network pharmacology was performed to explore the potential mechanism of differential metabolites in inducing DR. ResultsThrough the systematic review, 148 differential metabolites were obtained and the sphingolipid metabolic pathway attracted our attention. Plasma non-targeted lipidomics found that sphingolipids were accompanied by the development of DM into DR. In vitro experiments showed sphinganine and sphingosine-1-phosphate aggravated rat RMECs injury induced by high glucose, further increased MDA and ROS levels, and further decreased SOD activities and MMP. Network pharmacology revealed sphinganine and sphingosine-1-phosphate may induce DR by regulating the AGE-RAGE and HIF-1 signaling pathways. ConclusionsIntegrated systematic review, lipidomics and experiment verification reveal that abnormal sphingolipid metabolism facilitates DR by inducing oxidative stress on RMECs. Our study could provide the experimental basis for finding potential biomarkers for the diagnosis and treatment of DR.

Nrf2 protects against methamphetamine-induced nephrotoxicity by mitigating oxidative stress and autophagy in mice

Methamphetamine (MA) is a widely abused drug that can cause kidney damage. However, the molecular mechanism remains unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates resistance to oxidative and proteotoxic stress. In this study, we investigated the role of Nrf2 in MA-induced renal injury in mice. Nrf2 was pharmacologically activated and genetically knocked-out in mice. The animal model of MA-induced nephrotoxicity was established by injecting MA (2 mg/kg) intraperitoneally twice a day for 5 days. Histopathological alterations were shown in the MA-exposed kidneys. MA significantly increased renal function biomarkers and kidney injury molecule-1 (KIM-1) levels. MA decreased superoxide dismutase activity and increased malondialdehyde levels. Autophagy-related factors (LC3 and Beclin 1) were elevated in MA-treated mice. Furthermore, Nrf2 increased in the MA-exposed kidneys. Activation of Nrf2 may attenuate histopathological changes in the kidneys of MA-treated mice. Pre-administration of Nrf2 agonist significantly decreased KIM-1 expression, oxidative stress, and autophagy in the kidneys after MA toxicity. In contrast, Nrf2 knockout mice treated with MA lost renal tubular morphology. Nrf2 deficiency increased KIM-1 expression, oxidative stress, and autophagy in the MA-exposed kidneys. Our results demonstrate that Nrf2 may protect against MA-induced nephrotoxicity by mitigating oxidative stress and autophagy.

Beyond the surface: Consequences of methyl tert-butyl ether (MTBE) exposure on oxidative stress, haematology, genotoxicity, and histopathology in rainbow trout

Concerns have been raised about the possible environmental effects of methyl tert-butyl ether (MTBE), which is widely used as a gasoline additive. This research aimed to look at the consequences of MTBE contamination on rainbow trout (Oncorhynchus mykiss), emphasizing oxidative stress, genotoxicity, and histopathological damage. After determining the LC50-96 h value, the effects of sub-lethal doses of MTBE (0 (control), 90, 180, and 450 ppm) on rainbow trout were investigated. In fish tissues, the levels of oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) were measured. The comet assay, which measures DNA damage in erythrocytes, was used to determine genotoxicity. Histopathological examinations were done on liver and gill tissues to examine potential structural anomalies. The results of this study show that MTBE exposure caused considerable alterations in rainbow trout. Increased oxidative stress was demonstrated by elevated MDA levels and decreased SOD activity, while the comet assay revealed dose-dependent DNA damage, implying genotoxic effects. Histopathological study revealed liver and gill tissue abnormalities, including cell degeneration, necrosis, and inflammation. Overall, this research highlights the possible sub-lethal effects of MTBE contamination on rainbow trout, stressing the need of resolving this issue. Future research should look at the impacts of chronic MTBE exposure and the possibility of bioaccumulation in fish populations.

Protective Effect of Chrysin against Chlorpyrifos-Induced Metabolic Impairment and Pancreatitis in Male Rats.

This study was performed to evaluate the protective effects of chrysin (CH) on metabolic impairment and pancreatic injury caused by sub-chronic chlorpyrifos (CPF) intoxication in male rats. Forty male Wistar rats were randomly allocated into five groups (n=8). Intraperitoneal injections of chrysin (12.5, 25 and 50 mg/kg for 45 days) and CPF (10 mg/kg for 45 days) gavage were performed. Present findings indicated that the serum levels of glucose, total cholesterol, and lowdensity lipoprotein-cholesterol, as well as body weight, were increased in the CPF-exposed group. It was also found that CPF decreased superoxide dismutase activity as well as increased malondialdehyde and nitric oxide levels in the pancreatic tissue of exposed animals. Histopathological examination also confirmed the toxic effects of CPF on pancreatic tissue as mostly evidenced by infiltration of inflammatory cells and necrosis. CH (50 mg/kg) decreased blood glucose concentration (p < 0.05), TG (p < 0.05), and LDL-C in CPF-exposed animals. CH decreased the pancreas levels of MDA in all treated CPF-exposed groups versus the non-treated CPF-exposed group (p < 0.05, p < 0.001, p < 0.001, respectively). A significant difference was not seen in the NO and MDA levels and SOD activity between CH-treated (50 mg/kg) animals exposed to CPF and controls. A significant difference was not seen in the NO and MDA levels and SOD activity between CHtreated (50 mg/kg) animals exposed to CPF and controls. A significant difference was not seen in the NO and MDA levels and SOD activity between CH-treated (50 mg/kg) animals exposed to CPF and controls. In conclusion, CH could prevent initiate and progress of CPF-induced metabolic impairment by modulating oxidative stress in pancreatic tissue as a target organ of organophosphorus pesticides.

Intrahippocampal dose-dependent effects of aluminum injection on affective and cognitive response in male Wistar rat: potential role of oxidative stress

ABSTRACT Aluminum (Al) is one of the more widespread metals in the environment and the most abundant known for its neurotoxicity in both humans and animals and could be a potential factor inducing behavioral changes, oxidative stress (OS) and loss of synapses and neurons in the hippocampal areas. The main objective of this study is to determine the impact of a single intracerebral injection of AlCl3 at different doses on the right hippocampus on affective and cognitive behaviors, on levels of OS and morphological changes in male Wistar rats. Rats were treated with a single intrahippocampal injection of 2 μL of NaCl (0.9%) (Control) or successively with 2 μL of AlCl3 at 0.5 (Al-0.5), 1 (Al-1) and 2 mg/kg (Al-2). Five days following surgical procedures, neurobehavioral tests were performed for all groups and the brain were taken to evaluate OS markers and morphological changes in the hippocampus. The results clearly demonstrate that Al induced anxiety and depressive-like behaviors, cognitive deficit, increased lipid peroxidation, nitric oxide levels, decreased superoxide dismutase activity and mediates progressive alterations characterized by disorganization in the pyramidal cellular arrangement and a decrease in neuronal density in the CA3 hippocampal area. In conclusion, a single intrahippocampal injection of Al induced anxiety-like, depression-like, memory impairment, OS and morphological alterations in the hippocampus