Decrease In Superoxide Dismutase Levels Research Articles

Interplay of miRNAs and molecular pathways in spaceflight-induced depression: Insights from a rat model using simulated complex space environment.

Depression is a significant concern among astronauts, yet the molecular mechanisms underlying spaceflight-induced depression remain poorly understood. MicroRNAs (miRNAs) have emerged as potential regulators of neuropsychiatric disorders, including depression, but their specific role in space-induced depression remains unexplored. This study aimed to elucidate the involvement of candidate miRNAs (miR-455-3p, miR-206-3p, miR-132-3p, miR-16-5p, miR-124-3p, and miR-145-3p) and their interaction with differentially expressed genes (DEGs) in the neurobiology of spaceflight-induced depressive behavior. Using a simulated space environmental model (SCSE) for 21 days, depressive behavior was induced in rats, and candidate miRNA expressions and DEGs in the cortex region were analyzed through qRT-PCR and HPLC, respectively. Results showed that SCSE-exposed rats exhibited depressive behaviors, including anhedonia, increased immobility, and anxiousness compared to controls. Further analysis revealed increased hydrogen peroxide levels and decreased superoxide dismutase levels in the SCSE group, indicating abnormal oxidative stress in the cerebral cortex. Moreover, miRNA analysis demonstrated significant upregulation of miR-455-3p, miR-206-3p, miR-132-3p, and miR-16-5p expression. Among the DEGs identified, the in silico analysis highlighted their involvement in crucial pathways such as glutamatergic signaling, GABA synaptic pathway, and calcium signaling, implicating their role in spaceflight-induced depression. Protein-protein interaction analysis identified hub genes, including DLG4, DLG3, GRIN1, GRIN2B, GRIN2A, SYNGAP1, DLGAP1, GRIK2, and GRIN3A, impacting neuronal dysfunction functions in the cortex region of SCSE depressive rats. DLG4 emerged as a core gene regulated by miR-455-3p and miR-206-3p. Overall, this study underscores the potential of miRNAs as biomarkers for mood disorders and neurological abnormalities associated with spaceflight, advancing health sciences, and space health care.

Removal of intracellular antibiotic resistance genes by activating peroxymonosulfate with Co3O4@CNT catalytic membrane

The removal of antibiotic resistance genes (ARGs) is crucial to prevent the proliferation of antibiotic resistance. In this study, we successfully removed intracellular ARGs using the PMS/Co@CM system, which involved activating peroxymonosulfate (PMS) with a catalytic membrane composed of Co3O4 and carbon nanotubes. In the PMS/Co@CM system, 1O2 was the primary reactive oxygen species (ROS) responsible for intracellular ARGs removal. However, the presence of sulfamethoxazole (SMX) in the water samples significantly reduced the efficiency of removing intracellular ARGs in the PMS/Co@CM system although SMX was degraded by •SO4−. This can be attributed to the selective pressure of SMX, which elevated intracellular Superoxide Dismutase (SOD) levels while decreasing Propidium Iodide (PI) levels in cells. Consequently, this led to heightened antioxidant defense and reduced membrane permeability, thereby enhancing cell resistance to 1O2 generated by the PMS/Co@CM system. Encouragingly, a typical UV disinfection process facilitated the removal of residual intracellular ARGs in the effluent of the PMS/Co@CM system, attributed to decreased SOD levels and increased intracellular 1O2 by UV irradiation. These findings contribute to the theoretical understanding of effective ARGs removal and aid in the development of more efficient removal technologies.

Assessment of Antioxidant Enzyme Superoxide Dismutase (SOD) in Oral Cancer: Systematic Review and Meta-Analysis.

The present article aims to comprehensively review the existing literature on superoxide dismutase (SOD) levels, an antioxidant enzyme, in oral cancer. An extensive literature search was conducted across various databases, including PubMed, Wiley Online Library, Science Direct, and Cross Reference, spanning 1998-2023. At the outset, 1,177 articles were initially identified, and 907 studies were excluded due to irrelevance or duplication of the research question. Subsequently, 270 articles underwent screening evaluation, resulting in the selection of 85 articles meeting the inclusion criteria. Following this, 68 articles underwent a full-text comprehensive assessment, and ultimately, 39 were chosen for data extraction. The risk of bias in the designated articles was assessed using the Newcastle-Ottawa Scale. Finally, 13 studies were meticulously selected, offering consistent data for the ensuing meta-analysis. Meta-analysis was executed using comprehensive meta-analysis (CMA) version 3 software (Bio Stat Inc., Englewood, NJ, USA). The meta-analysis findings revealed a statistically significant decrease in SOD levels in both erythrocyte samples (P < 0.001) and tissue samples (P < 0.05) among individuals with oral cancer (OSCC) compared to the normal control group. Conversely, the analysis of three studies on salivary samples demonstrated a significant increase (P < 0.05) in SOD levels in the oral cancer group compared to the healthy controls. This systematic review underscores a statistically significant decline in SOD levels observed across diverse bio-samples in individuals with oral cancer, indicating an excess of oxidative stress (OS). Additional research is needed to delve into the relationship between SOD levels and clinic-pathological prognostic markers within the oral cancer cohort. Such investigations have the potential to significantly contribute to the development of prognostic tools grounded in OS, thereby guiding strategies for treatment planning.

Relationship between phthalates exposure, risk of decreased ovarian reserve, and oxidative stress levels.

Phthalates (PAEs), a group of environmental endocrine disruptors, are associated with oxidative stress and have adverse effects on female ovarian reserves. However, this association has been poorly investigated, particularly with respect to clinical evidence. In this study, we provided clinical evidence of a relationship between exposure levels of PAEs, oxidative stress and decreased ovarian reserve (DOR). Firstly, the urinary concentrations of metabolites of PAEs were measured by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), and the biomarkers of oxidative stress, malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), were determined. Finally, statistical analyses were conducted to describe the relationship between the PAEs exposure, oxidative stress and DOR. We found that the levels of monomethyl phthalate (MMP), monoisobutyl phthalate (MiBP), mono-(2-ethylhexyl) phthalate (MEHP), and mono-(2-ethyl-5-hydroxypentyl) phthalate (MECPP) in the DOR group were significantly higher than those in the control group. There was a significant negative association between AMH and MMP, MiBP levels. and a significant positive association between FSH and MMP levels. PAEs exposure was also associated with a significant increase in MDA levels and decrease in SOD levels. In conclusion, the exposure of PAEs was closely associated with DOR, potentially mediated by oxidative stress pathways; however, small sample size was a limitation in this study.

Oxidative stress a potent risk factor for thyroid diseases in young pregnant females.

Objective: To evaluate the potent role of oxidative stress in thyroid disease development and progression in young pregnant females during 1st and second trimesters compared with matched healthy pregnant females of the same gestational age. Study Design: Cross-sectional Comparative study. Setting: Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Pakistan. Samples were collected at the Punjab Institute of Nuclear Medicine (PINUM), Faisalabad, and the Department of Obstetrics at DHQ Hospital, Chiniot. Period: July 2019 to July 2021. Material &amp; Methods: Thyroid disease- comorbid pregnant women and euthyroid pregnant women were compared for serum levels of oxidative stress markers and antioxidants. The markers were evaluated between 68 healthy subjects in Group A and 43 subjects in Group B known for having thyroid diseases. Blood samples were taken under highly sterile conditions after gaining written consent from all subjects and stored at –8°c to –30°c. A spectrophotometer at 532nm was used to measure serum concentrations of oxidative stress markers. ELISA kits were used to determine serum levels of triiodothyronine, thyroxin, and thyroid-stimulating hormone. Data was analyzed using independent student t-test, multiple logistic regression, and receiver operating characteristic curve (ROC) analysis using SPSS version 25. Results: Group A and Group B had a mean age of 26.07±4.88 and 29.19±4.17 years, respectively. Pregnant women having thyroid dysfunction had decreased superoxide dismutase levels (0.05±0.01 nmol/ml) than group A (0.06±0.01). Other indicators of lipid peroxidation showed a non-significant mean difference compared between both groups (p&gt;0.05). Multiple linear regression studies revealed healthy pregnant women with a positive thyroid medication history had higher SOD levels among group B than those without antithyroid medicine, with a Beta coefficient of +0.26 and p=0.04. According to ROC curve analysis, the Superoxide Dismutase biomarker area under ROC was 67.25% at p=0.002. Thus, it may be used as a diagnostic and predictive biomarker. A cutoff value of 51.5pg/ml was proposed, at which sensitivity is 79% and specificity is 69%. It can be a diagnostic and predictive biomarker. Conclusion: The results of the current study concluded that oxidative stress can be considered a potent risk factor for the development and progression of thyroid disease in young pregnant females.

Treatment strategies with vitamin E and C in autologous intraperitoneal ovarian transplantation and its impact on ovarian surface epithelium and follicle reserve

The objective of this study was to assess the impact of Vitamin E (Vit E) and Vitamin C (Vit C) on markers of the oxidant-antioxidant system, ovarian follicle reserves, and the surface epithelium in autologous intraperitoneal ovarian transplantation conducted in rats. The study aimed to investigate how these antioxidants influence various aspects related to transplantation outcomes, including oxidative stress markers, the preservation of follicle reserves, and the condition of the surface epithelium. A total of 20 adult female Wistar Albino rats were included in the study and randomly assigned to four different groups. Group 1, consisting of 5 rats, served as the control group and underwent a surgical procedure where their abdomens were opened and closed without any further intervention. Group 2, also consisting of 5 rats, underwent ovarian transplantation. In Group 3, comprising 5 rats, an intraperitoneal (IP) administration of 20 mg/kg body weight (b.w.) of Vitamin E (Vit E) was given 15 min prior to ovarian transplantation. Lastly, in Group 4, which included 5 rats, an IP administration of 50 mg/kg body weight (b.w.) of Vitamin C (Vit C) was given 15 min before ovarian transplantation. Vaginal cytology was performed in order to monitor the estrus phase in the rats. Biochemically, tissue and serum malondialdehyde (MDA) levels and erythrocyte superoxide dismutase (SOD) levels were measured. Histopathologically, the number of dysplastic changes in the ovarian surface epithelium and primordial, primary, secondary, Graaffian, and atretic follicles were examined. Dysplastic changes in the surface epithelium of Group 2 were found to be significantly higher than in Group 1 and 4 (p < 0.02). In Group 2, the ovarian follicle reserves (primordial, primary, secondary, and Graaffian follicles) were significantly lower than in other groups (p < 0.02). In addition, a significant decrease in SOD levels was found in Group 2 compared to other groups (p < 0.02). The study showed that Vit E and Vit C in autologous intraperitoneal ovarian transplantation preserved the ovarian follicle reserve. Vit C was found to be more effective than Vit E.

Evaluation of Superoxide Dismutase, an Antioxidant Enzyme, in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

Objective: The objective is to qualitatively and quantitatively review the published literature on superoxide dismutase (SOD) levels in oral squamous cell carcinoma (OSCC). Materials and Methods: MEDLINE (via PubMed), SCOPUS, Science Direct, Cochrane Library, ProQuest, Google Scholar, and gray literature were comprehensively searched. Human clinical studies published between 2000 and 2021 were included. The Newcastle–Ottawa Scale was used to evaluate the risk of bias in the studies. Results: Of the 873 articles screened, six studies were included, evaluating 640 patients (554 OSCC cases and 113 controls). SOD levels in OSCC subjects were significantly lesser (P &lt; 0.01) compared to healthy controls in spectrophotometry analysis, whereas its immuno-expression was significantly higher in the OSCC tissue samples in immunohistochemistry. In the meta-analyses related to SOD analysis by spectrophotometry, the overall effect size of tissue SOD in OSCC and control group were 8.51 and 11.62 U/mg protein, respectively. In the meta-analyses related to SOD analysis by immunohistochemistry, the overall effect size of tissue SOD in OSCC was 55.55% and 3.61% for cell staining, respectively. Conclusion: Decreased SOD levels in OSCC tissue samples in spectrophotometry and high immunoexpression in immunohistochemistry accurately reflect increased oxidative stress (OS) levels. Further studies are required to understand the increase in SOD levels in OSCC tissue. Correlation analysis between SOD levels and established clinicopathological prognostic markers could aid in formulation of OS-based prognostication and treatment planning.

A study to demonstrate the potential of Anabolic Androgen Steroid to activate oxidative tissue damage, nephrotoxicity and decline endogenous antioxidant system in renal tissue of Adult Wistar Rats.

Anabolic Androgenic steroids (AAS) are abused and reports have been made on their deleterious effects on various organs. It is imperative to report the mechanism of inducing oxidative tissue damage even in the presence of an intracellular antioxidant system by the interaction between lipid peroxidation and the antioxidant system in the kidney. Twenty (20) adult male Wistar rats used were grouped into: A- Control, BOlive oil vehicle, C- 120mg/kg of AAS orally for three weeks, and D- 7 days withdrawal group following 120mg/kg/ 21days of AAS intake. Serum was assayed for lipid peroxidation marker Malondialdehyde (MDA) and antioxidant enzyme -superoxide Dismutase (SOD). Sectioned of kidneys were stained to see the renal tissue, mucin granules, and basement membrane. AAS-induced oxidative tissue damage, in the presence of an endogenous antioxidant, is characterized by increased lipid peroxidation and decreased SOD level which resulted in the loss of renal tissue cells membrane integrity which is a characteristic of the pathophysiology of nephron toxicity induced by a toxic compound. However, this was progressively reversed by a period of discontinuation of AAS drug exposure.

Antioxidant, anti-inflammatory, and anti-fibrotic properties of olive leaf extract protect against L-arginine induced chronic pancreatitis in the adult male albino rat.

Chronic pancreatitis (CP) is an inflammatory disease affects the pancreas with upcoming fibrosis and notable parenchymal destruction. CP poses a high risk for pancreatic carcinoma. The present study aimed to investigate, for the first time up to our knowledge, the effect of olive leaf extract on L-arginine induced CP with referral to some of its underlying mechanisms. Forty adult male albino rats were divided equally into four groups; control, olive leaf extract treated (200 mg/kg orally once daily), CP group (300 mg L-arginine/100 g body weight intraperitoneally, once daily for 3 weeks then every 3 days for the subsequent 3 weeks), and CP treated with olive leaf extract group. At the end of the experiment, body weight, serum glucose, serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), serum amylase and lipase as well as tissue superoxide dismutase (SOD), and malondialdehyde (MDA) levels were assessed. Pancreatic tissues were subjected to histological and immuno-histochemical studies. The CP group revealed significant decrease in body weight and increase in serum glucose, serum insulin, HOMA-IR score, serum amylase, and serum lipase levels. Significant increase in MDA level and decrease in SOD level were detected. Marked degenerative changes and fibrosis were detected. Upregulation of alpha smooth muscle actin (α-SMA), transforming growth factor beta (TGF-β), caspase-3, and interleukin-6 (IL-6) immunoreactions were implicated in CP pathogenesis. Olive leaf extract alleviated all the examined parameters via its-antioxidant, anti-inflammatory, and anti-fibrotic properties. Olive leaf extract can protect against CP and restore pancreatic functions.

Antioxidant Status in Serum of Long-term Areca Nut chewers and Oral Squamous Cell Carcinomas Patients

Aim: This study was carried out to investigate implications of serum antioxidant status in people with long-term areca nut chewers and oral squamous cell carcinoma (OSCC) patients. Materials and Methods: Serum samples were collected from areca nut chewers, OSCC patients, and control of both genders between the ages of 15 and 60 years. Superoxide dismutase (SOD), total antioxidant capacity (TAC), uric Acid, and protein were estimated using ELISA reader, semi-automatic biochemical analyzer, and spectrophotometer. Results: SOD level in OSCC patients was decrease when compared to control and areca nut chewers indicate a low antioxidant profile. Yet, a decrease in SOD level in areca nut chewers when compared to control suggests that areca nut chewers are also prone to oxidative stress. TAC a known cancer biomarkers are known to increase in tobacco and areca quid’s consumers. Increase serum TAC level in OSCC and areca nut chewers when compared to healthy control could further justify that areca nut chewers population are prone to OSCC. Our studies also showed that decrease uric acid level in areca nut chewers corresponds to decrease in free radical scavenging activity which relates to our SOD level in our earlier finding. Increase protein level was also observed in OSCC patients when compared to areca nut chewers and controls. Although, there was no significant change between areca nut chewers and controls, increase protein level in areca nut chewers indicates violation to the integrity of capillary bed or mucosal lining as occurs in oral neoplasia which can cause increase protein synthesis. Conclusion: Areca nut chewers can alter serum antioxidant enzymes and increase OSCC cancer biomarker. Hence, maintaining the antioxidants status can help limit the progression of precancerous condition toward malignancy.

A Potential In Vitro 3D Cell Model to Study Vascular Diseases by Simulating the Vascular Wall Microenvironment and Its Application.

Background: Current in vitro vascular models are too simple compared with the real vascular environment. In this research, a novel in vitro 3D vascular disease model that simulated the vascular microenvironment was introduced. Methods: This model was mainly established by low shear stress and co-culture of endothelial cells and smooth muscle cells. Characterization and reproduction of the pathological state of the 3D model were determined. The effect of two clinical drugs was verified in this model. The difference of drug screening between a traditional oxidative-damaged cell model and this 3D model was determined by HPLC. Results: This model presented many disease markers of vascular diseases: abnormal cellular shape, higher endothelial cell apoptotic rate and smooth muscle cell migration rate, decreased superoxide dismutase level, and increased malondialdehyde and platelet-derived growth factor level. The drugs effectively reduced the disease indices and relieved the damage caused by low shear stress. Compared to the traditional oxidative-damaged cell model, this 3D model screened different active components of Salviae Miltiorrhizae extract, and it is closer to clinical studies. Conclusions: These results suggest that the 3D vascular disease model is a more efficient and selective in vitro study and drug screening platform for vascular diseases than previously reported in vitro vascular disease models.

Lidocaine attenuates hypoxia/reoxygenation‑induced inflammation, apoptosis and ferroptosis in lung epithelial cells by regulating the p38 MAPK pathway

Lung ischemia-reperfusion (I/R) injury poses a serious threat to human health, worldwide. The current study aimed to determine the role of lidocaine in A549 cells, in addition to the involvement of the p38 MAPK pathway. Oxygen deprivation/reoxygenation-induced A549 cells were utilized to simulate I/R injury in vitro. Cell viability and apoptosis were detected using MTT and TUNEL assays, respectively. The levels of IL-6, IL-8, TNF-α, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase, iron and reactive oxygen species (ROS) were measured using corresponding commercial kits. The corresponding protein expression levels were also measured using western blotting. Moreover, a monolayer cell paracellular permeability assay was performed to determine the permeability of A549 cells. The results demonstrated that, whilst lidocaine had no influence on untreated A549 cells, it significantly increased the viability of hypoxia/reoxygenation (H/R)-induced A549 cells. A549 cell apoptosis and the release of inflammatory cytokines in the H/R group were decreased after the addition of lidocaine. When compared with the H/R group, increased MDA level and decreased SOD level were observed in H/R-induced A549 cells following lidocaine treatment. In addition, the permeability of H/R-induced A549 cells was markedly decreased following lidocaine treatment. Compared with the H/R group, the expression levels of tight junction and ferroptosis-related proteins were significantly upregulated by lidocaine, whereas the expression of transferrin was downregulated. However, p79350, an agonist of p38, reversed the effects of lidocaine on H/R-induced A549 cells. In conclusion, lidocaine exerted a protective role in HR-induced lung epithelial cell injury, which may serve as a potential agent for the treatment of patients with lung I/R injury.

Effect of interferon regulatory factor 2 on inflammatory response and oxidative stress in lipopolysaccharide-induced acute kidney injury.

Interferon regulatory factor (IRF) 2 plays an important role in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). In this study, we explored the effects of IRF2 on apoptosis, inflammation, and oxidative stress in AKI C57BL/6 male mouse model and HEK293 cells following LPS treatment. To determine the effect of IRF2, short hairpin RNAs in mice and small interfering RNAs in cells were used to knockdown IRF2 expression. IRF2 expression, apoptosis, and severity of inflammatory and oxidative stress in mice and cells were measured. IRF2 levels were upregulated in LPS-treated mice and cells. IRF2 knockdown suppressed the levels of creatinine, blood urea nitrogen, and kidney injury molecule 1 and decreased the renal injury score in mice. Furthermore, IRF2 knockdown inhibited apoptosis and decreased the levels of inflammatory, reactive oxygen species (ROS), and malondialdehyde (MDA), but increased superoxide dismutase (SOD) levels in mice and cells. Furthermore, we found that the Janus kinase (JAK)/ signal transducer and activator of transcription pathway activated by LPS was inhibited by knockdown of IRF2, and enhanced by IRF2 overexpression. IRF2 overexpression increased cell apoptosis, inflammation, and ROS and MDA levels, and decreased SOD levels. However, the effect of IRF2 overexpression was reversed by the JAK inhibitor tofacitinib. Knockdown of IRF2 reduced LPS-induced renal tissue injury in vivo and in vitro through anti-inflammatory and antioxidant stress effects.

Mechanism of miRNA-141-3p in Calcium Oxalate-Induced Renal Tubular Epithelial Cell Injury via NLRP3-Mediated Pyroptosis

Background/Aims: Renal calculi represent a prevalent disorder associated with mineral deposition in renal calyces and the pelvis. Aberrant microRNA (miRNA) expression is implicated in renal injury. This study investigated the mechanism of miR-141-3p in calcium oxalate (CaOx) crystal-induced renal tubular epithelial cell (RTEC) injury. Methods: Human RTECs HK-2 cells were treated with CaOx crystals to induce RTEC injury. Cell viability was evaluated using Cell Counting Kit-8 assay, and apoptosis was measured using flow cytometry. The contents of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), interleukin (IL)-1β, and IL-18 were measured using enzyme-linked immunosorbent assay kits. The expressions of NLRP3, cleaved caspase-1, and GSDMD-N were detected using Western blot. miR-141-3p and NLRP3 expressions were determined using reverse transcription quantitative polymerase chain reaction. The binding of miR-141-3p and NLRP3 was validated using a dual-luciferase assay. The role of NLRP3 in the protection of miR-141-3p on RTEC injury was verified using functional rescue experiments. Results: CaOx crystals induced RTEC injury, manifested as attenuated cell viability, enhanced apoptosis, elevated intracellular LDH and MDA levels, and decreased SOD level. Pyroptosis of RTECs was enhanced by CaOx crystal induction, evidenced by elevated expressions of cleaved caspase-1, GSDMD-N, IL-1β, and IL-18. miR-141-3p expression was reduced in CaOx crystal-induced RTECs. miR-141-3p overexpression alleviated CaOx crystal-induced RTEC injury and suppressed pyroptosis of RTECs. miR-141-3p bound to NLRP3 and thereby repressed NLRP3 expression. NLRP3 overexpression reversed the protective effect of miR-141-3p overexpression on RTECs. Conclusion: miR-141-3p repressed NLRP3-mediated pyroptosis by suppressing NLRP3 expression, thus protecting CaOx crystal-induced RTEC injury.

Effects of nicorandil on systemic inflammation and oxidative stress induced by percutaneous coronary intervention in patients with coronary heart disease.

ObjectiveThe present study investigated the effects of a bolus intracoronary injection of nicorandil on systemic inflammation and oxidative stress induced by percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD).MethodsPatients undergoing coronary angiography (CAG) were enrolled into the CAG group (n = 30). Patients undergoing PCI were randomly divided into the PCI (n = 30) and PCI + nicorandil groups (n = 30).ResultsBlood taken from patients in the placebo group 24 hours after PCI exhibited significant increases in the expression of inflammatory indicators and mild increases in the expression of anti-inflammatory indicators. The intracoronary injection of nicorandil reversed the elevation of inflammatory indicators and significantly increased the levels of anti-inflammatory indicators in the blood of patients with PCI. Blood taken from patients in the placebo group 24 hours after PCI also displayed significant decreased superoxide dismutase levels and increased malondialdehyde levels. Nicorandil treatment reversed these changes of oxidative stress marker levels.ConclusionsThese results indicated the possible medical application of intracoronary injections of nicorandil for reducing systemic inflammation and oxidative stress in the peripheral blood of patients undergoing PCI.

Hepatotoxic Effects of Ethanolic leaf Extract of Breynia nivosa (Snow bush) in Wistar rats

The hepatotoxic effects of ethanolic leaf extract of Breynia nivosa in male albino Wistar rats were studied. The Breynia nivosa leaves were extracted using 70% ethanol. The phytochemicals were evaluated and found to contain – tannin, flavonoids, saponins, cardiac glycosides and cyanogenic glycosides. Twenty (20) adult male albino Wistar rats were randomly divided into four (4) groups – three tests of A, B, C and one control – and were administered with 400mg/kg, 200mg/kg and 100mg/kg of the ethanolic leaf extract of Breynia nivosa respectively for 21days after two weeks of acclimatization. The animals were sacrificed under anaesthesia after the experiment and blood samples collected for determination of the antioxidant enzymes (superoxide dismutase and glutathione peroxidase), malondialdehyde, and liver enzyme: aspartate transaminase (AST), alkaline phosphatase (ALP), and alanine transaminase (ALT). The results showed that there was a significant decrease in superoxide dismutase level (P&lt;0.05). Changes in other markers (malondialdehyde and glutathione peroxidase) were however not statistically significant (P&gt;0.05) when compared with the control. The extract significantly increased ALT, AST, ALP levels (p&lt;0.05). Hence Breynia nivosa may be toxic and caution should be exercised in its consumption.

Bardoxolone-Methyl Prevents Oxidative Stress-Mediated Apoptosis and Extracellular Matrix Degradation in vitro and Alleviates Osteoarthritis in vivo.

PurposeOxidative stress-induced chondrocyte apoptosis and extracellular matrix (ECM) degradation plays an important role in the progression of osteoarthritis (OA). Bardoxolone methyl (BM), a semisynthetic triterpenoid, exerts strong effect against oxidative stress. The purpose of the present study was to determine the effectiveness of bardoxolone-methyl (BM) in preventing oxidative stress-induced chondrocyte apoptosis and extracellular ECM degradation in vitro and the role of alleviating OA progression in vivo.MethodsOxidative damage was induced by 25 mM tert-butyl hydroperoxide (TBHP) for 24 h in rat chondrocytes. 0.025 and 0.05 µM bardoxolone-methyl (BM) were used in vitro treatment. Ex-vivo cartilage explant model was established to evaluate the effect of BM on oxidative stress-induced ECM degradation. The mouse OA model was induced by surgical destabilization of the medial meniscus.ResultsIn vitro, 0.025 and 0.05 µM BM reduced TBHP-induced excessive ROS generation, improved cell viability, increased malondialdehyde level and decreased superoxide dismutase level. 0.025 and 0.05 µM BM prevented TBHP-induced mitochondrial damage and apoptosis in chondrocytes BM activated heme oxygenase-1 (HO-1)/NADPH quinone oxidoreductase 1 (NOQ1) signaling pathway through targeting nuclear factor erythroid derived-2-related factor 2 (Nrf2). Additionally, BM treatment enhanced the expression levels of aggrecan and collagen II and inhibited the expression levels of matrix metalloproteinase 9 (MMP 9), MMP 13, Bax and cleaved-caspase-3. BM increased proteoglycan staining area and IOD value in ex vivo cultured experiment cartilage explants and improved the OARSI score, stands, max contact mean intensity, print area and duty cycle in mouse OA model.ConclusionBM prevented oxidative stress-induced chondrocyte apoptosis and ECM degradation in vitro and alleviated OA in vivo, suggesting that BM serves as an effective drug for treatment with OA.

Cytotoxic response of phagocytes in patients newly infected with pulmonary Mycobacterium tuberculosis determined using plasma tumor necrosis factor-alpha, malondialdehyde, and superoxide dismutase: an observational study

Abstract Objective: Pulmonary Mycobacterium tuberculosis infection can trigger cellular and humoral innate immune responses, which may cause death of the pathogen and or host cells/tissue. We aimed to determine the cytotoxic response of phagocytes in patients with pulmonary Mycobacterium tuberculosis infection based on plasma tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Methods: In this observational study, patients newly infected with pulmonary Mycobacterium tuberculosis (n = 31; age 37–62 years) and age-matched uninfected volunteers (n = 50) were recruited as test and control volunteers, respectively in Owo, Nigeria. The study protocol was reviewed and approved by the Research and Ethics Committee of the Department of Medical Laboratory Science, Achievers University, Owo, Nigeria (AUO/MLS/VII/2009/212). Anti-hepatitis C virus, human immunodeficiency virus antigen/antibody, hepatitis B virus surface antigen, and plasma TNF-α were determined by enzyme-linked immunosorbent assay, SOD, and MDA were determined by colorimetry, Plasmodium by Giemsa thick blood film staining, and acid-fast bacilli in sputum were detected by Ziehl–Neelsen staining. Results: All participants had normal blood glucose levels and tested negative for human immunodeficiency virus antigen/antibody, anti-hepatitis C virus, hepatitis B virus surface antigen, and Plasmodium spp., and had no medical history of cancer. Infected patients had significantly higher plasma MDA and TNF-α levels and significantly lower SOD levels compared with control subjects (all P &lt; 0.05). Conclusion: Mycobacterium tuberculosis infection elicited a cytotoxic response by phagocytes, evidenced by significant increases in MDA and TNF-α and a significant decrease in SOD levels.

Long non-coding RNA LUCAT1 inhibits myocardial oxidative stress and apoptosis after myocardial infarction via targeting microRNA-181a-5p

ABSTRACT This study hoped to explore the effects and mechanism of long non-coding RNA (lncRNA) LUCAT1 regulating microRNA-181a-5p (miR-181a-5p) on oxidative stress and apoptosis of cardiomyocytes induced by H2O2. Totally, 72 patients with acute myocardial infarction (AMI) were included. H9c2 cardiomyocytes were cultured in vitro, and the H2O2 model of cardiomyocytes was established. The expression levels of LUCAT1 and miR-181a-5p were detected by qRT-PCR after H2O2 induction. The contents of reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) in cells were detected. The survival rate of the cells was detected by the Cell Counting Kit-8 (CCK-8) method; the apoptosis was detected by flow cytometry. The luciferase reporter experiment and quantitative real-time PCR (qRT-PCR) were used to verify the targeted relationship between LUCAT1 and miR-181a-5p. LUCAT1 was lowly expressed in the AMI patients. After H2O2 induction, the expression of LUCAT1 in H9c2 cells lessened significantly, while the expression of miR-181a-5p elevated significantly (P < 0.001). Transfection of p-LUCAT1 significantly reversed the decreased SOD levels, the increased MDA and ROS content, and the elevated tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in H2O2-stimulated cells (P < 0.001). Upregulation of LUCAT1 contributed to the mitigation of H2O2 injury by promoting viable cells and repressing apoptotic cells (P < 0.01). LUCAT1 targeted miR-181a-5p and negatively regulated miR-181a-5p expression (P < 0.001). Collectively, LUCAT1 played a protective role on oxidative stress injury, inflammation, viability, and apoptosis of cardiomyocytes induced by H2O2 via regulating miR-181a-5p.

Oxymatrine Ameliorates Memory Impairment in Diabetic Rats by Regulating Oxidative Stress and Apoptosis: Involvement of NOX2/NOX4.

Oxymatrine (OMT) is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait and has been shown to exhibit a diverse range of pharmacological properties. The aim of the present study was to investigate the role of OMT in diabetic brain injury in vivo and in vitro. Diabetic rats were induced by intraperitoneal injection of a single dose of 65 mg/kg streptozotocin (STZ) and fed a high-fat and high-cholesterol diet. Memory function was assessed using a Morris water maze test. A SH-SY5Y cell injury model was induced by incubation with glucose (30 mM/l) to simulate damage in vitro. The serum fasting blood glucose, insulin, serum S100B, malondialdehyde (MDA), and superoxide dismutase (SOD) levels were analyzed using commercial kits. Morphological changes were observed using Nissl staining and electron microscopy. Cell apoptosis was assessed using Hoechst staining and TUNEL staining. NADPH oxidase (NOX) and caspase-3 activities were determined. The effects of NOX2 and NOX4 knockdown were assessed using small interfering RNA. The expression levels of NOX1, NOX2, and NOX4 were detected using reverse transcription-quantitative PCR and western blotting, and the levels of caspase-3 were detected using western blotting. The diabetic rats exhibited significantly increased plasma glucose, insulin, reactive oxygen species (ROS), S-100B, and MDA levels and decreased SOD levels. Memory function was determined by assessing the percentage of time spent in the target quadrant, the number of times the platform was crossed, escape latency, and mean path length and was found to be significantly reduced in the diabetic rats. Hyperglycemia resulted in notable brain injury, including histological changes and apoptosis in the cortex and hippocampus. The expression levels of NOX2 and NOX4 were significantly upregulated at the protein and mRNA levels, and NOX1 expression was not altered in the diabetic rats. NOX and caspase-3 activities were increased, and caspase-3 expression was upregulated in the brain tissue of diabetic rats. OMT treatment dose-dependently reversed behavioral, biochemical, and molecular changes in the diabetic rats. In vitro, high glucose resulted in increases in reactive oxygen species (ROS), MDA levels, apoptosis, and the expressions of NOX2, NOX4, and caspase-3. siRNA-mediated knockdown of NOX2 and NOX4 decreased NOX2 and NOX4 expression levels, respectively, and reduced ROS levels and apoptosis. The results of the present study suggest that OMT alleviates diabetes-associated cognitive decline, oxidative stress, and apoptosis via NOX2 and NOX4 inhibition.