Catalase Gene Expression Research Articles

Effect of in ovo feeding of γ-aminobutyric acid combined with embryonic thermal manipulation on hatchability, growth, and hepatic gene expression in broilers.

This study investigated the effects of in ovo feeding of γ-aminobutyric acid (GABA) and embryonic thermal manipulation (ETM) on growth performance, organ indices, plasma biochemical parameters, hepatic antioxidant levels, and expression of lipid metabolism-related genes in broilers. Two hundred and fifty eggs were assigned to one of four treatments: control eggs incubated under standard conditions (CON); eggs that received an in ovo injection of 10% GABA on day 17.5 of incubation (G10); thermally manipulated eggs between days 10 and 18 of incubation at 39.6°C for 6 h daily (TM); and eggs that received both treatments during incubation (G10+TM). After 28 days of rearing, five birds per treatment were selected for blood and organ sampling. No differences were found in hatchability or growth parameters among different treatment groups. Hepatic gene expression of catalase (CAT) and glutathione peroxidase 1 (GPx1) was upregulated (p = 0.046 and p = 0.006, respectively) in the G10+TM group, while that of nuclear factor erythroid 2-related factor 2 (NRF2) was upregulated (p = 0.039) in the G10 group. In addition, the relative gene expression of NADPH oxidase 1 (NOX1) was significantly lower (p = 0.007) in all treatment groups than that in the CON group. Hepatic fatty acid synthase (FAS) levels and average daily feed intake (ADFI) of last week showed a positive correlation (r = 0.50, p = 0.038). In contrast, the relative gene expression of the extracellular fatty acid-binding protein (EXFAB) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were positively correlated (r = 0.48, p = 0.042 and r = 0.50, p = 0.031) with the overall ADFI of birds. Taken together, the results of this study suggest that the combination of in ovo feeding of GABA and ETM can enhance hepatic antioxidant function in broilers.

P604: CATALASE EXPRESSION IN LEUKEMIA CELLS IS CONTROLLED BY GENETIC AND EPIGENETIC MECHANISMS

Background: Chronic lymphocytic leukemia (CLL) is the most prevalent form of leukemia in Western countries. It is an incurable disease characterized by an extremely variable clinical course and response to treatment. We have recently shown that high catalase (CAT) expression identifies a more aggressive clinical behavior in CLL. However, molecular mechanisms controlling catalase expression in leukemia cells are still poorly characterized. The rs1001179 single nucleotide polymorphism (SNP) as well as DNA methylation in the CAT promoter have been shown to regulate CAT expression in various cell types. Aims: With the aim to characterize regulatory mechanisms underlying differential expression of catalase in CLL, in this study we investigated the role of rs1001179 SNP and CpG Island II methylation encompassing this SNP in the regulation of CAT expression. Methods: Peripheral blood mononuclear cells (PBMC) from 55 CLL patients and 50 healthy donors (HD) were used for the study. CAT mRNA levels were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). DNA samples were genotyped for the rs1001179 SNP using Restriction Fragment Length Polymorphism (RFLP)-PCR. Bioinformatic analysis was used to predict transcription factor (TF) binding to SNP sequences. Chromatin Immunoprecipitation (ChIP)-qPCR was performed to validate predicted TF binding sites. Methylation levels of CpG sites within the CAT promoter was determined by pyrosequencing of bisulfite-converted DNA. Results: The rs1001179 SNP genotyping showed that CLL cells harboring the T allele exhibited a significantly higher catalase expression compared with cells bearing the CC genotype. Interestingly, bioinformatic analysis predicted that the SNP provide distinct binding sites for various TF, including ETS-1 and GR-β. ChIP assay confirmed that CAT promoter harboring the T -but not C- allele was accessible to ETS-1 and GR-β, but not to the other analyzed TFs. In addition, CLL cells exhibited lower methylation levels within the CAT promoter compared with HD B cells, in line with the higher catalase mRNA and protein levels expressed by CLL versus HD B cells. Moreover, methylation levels negatively correlated with CAT expression in CLL cells. Remarkably, inhibition of methyltransferase activity in leukemic cells induced a significant increase of CAT mRNA and protein levels, thus showing that DNA methylation could control catalase expression in CLL. Moreover, expression of DNA methyl transferase 1 (DNMT1) resulted significantly reduced in CLL cells compared with HD B cells and inversely correlated with CAT expression in CLL, thus suggesting that differences in methylation levels underlying catalase expression could be driven by the DNMT1 enzyme. Finally, modeling analysis showed that the CT/TT genotypes exhibited a lower methylation and a higher CAT expression level, suggesting that the rs1001179 T allele and methylation cooperate in inducing CAT gene expression. Summary/Conclusion: Our data show that SNP as well as methylation of the catalase promoter are involved in controlling catalase expression in CLL. The key advance of this study is to provide new insights into the regulatory mechanisms underlying differential expression of catalase in leukemic cells, which is of clinical relevance in CLL. Moreover, our study may form the basis for future challenges aimed at developing combinatorial therapies targeting catalase regulatory pathways.

Effect of Selenium on the Iron Homeostasis and Oxidative Damage in Brain and Liver of Mice.

Selenium is an essential trace element that maintains normal brain function, mainly due its antioxidant properties. Although the amount of Se in the body is tightly regulated by the liver, both an excess of and deficiency in Se can modulate the cellular redox status and affect the homeostasis of other essential elements for both humans and animals. The aim of this study was to determine the effect of inorganic selenium excess on oxidative stress and iron homeostasis in brain and liver of laboratory BALB/c mice, which were supplemented with Na2SeO3 solution (0.2 mg and 0.4 mg Se/kg body weight) for 8 weeks. The content of the lipid peroxidation product malondialdehyde and antioxidant enzyme catalase activity/gene expression were used as markers of oxidative damage and were evaluated by spectrophotometric assays. Selenium and iron concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). Catalase gene expression was analyzed by qRT-PCR and ΔΔCt methods. Our results showed that doses of 0.2 mg Se and 0.4 mg Se caused a relatively low accumulation of Se in the brain of mice; however, it induced a 10-fold increase in its accumulation in the liver and also increased iron accumulation in both tested organs. Both doses of Se increased the content of malondialdehyde as well as decreased catalase activity in the liver, while the 0.4 mg Se dose has also activated catalase gene expression. Brain of mice exposed to 0.2 mg Se showed reduced lipid peroxidation; however, the exposure to 0.4 mg of Se increased the catalase activity as well as gene expression. One may conclude that exposure to both doses of Se caused the accumulation of this micronutrient in mice brain and liver and have also provided a disrupting effect on the levels of iron. Both doses of Se have triggered oxidative liver damage. In the brain, the effect of Se was dose dependent, where −0.2 mg of Se provided antioxidant activity, which was observed through a decrease in lipid peroxidation. On the contrary, the 0.4 mg dose increased brain catalase activity as well as gene expression, which may have contributed to maintaining brain lipid peroxidation at the control level.

1444-P: Knockdown of Etv5 Impairs Viability of Pancreatic Beta Cells by Enhancing ROS Production

Introduction: The transcription factor ETV5 regulates various biological processes such as cell proliferation and apoptosis, and activates a whole string of obesity- and diabetes-related genes. ETV5 is involved in tissue protection since mice with pancreatic loss of Etv5 show increased severity of pancreatitis and delayed tissue recovery. Here, we investigate the role of Etv5 knockdown (KD) on survival of injured endocrine pancreatic beta cells. Methods: We generated INS-1E beta cells with doxycycline (dox) -inducible lentiviral Etv5 sh-RNA knock-down (KD) . Cellular stress was induced by streptozotocin (STZ) and palmitate (PA) . We assessed viability (MTS) , apoptosis (caspases-3/7 activation) , necrosis (assay) , ER stress (BiP and CHOP gene expression) , oxidative stress (ROS production) and gene expression of SOD1, SOD2 and Catalase. Results: Etv5 KD significantly increases STZ/PA-induced loss of viability without changes in apoptosis but with increased necrosis. Etv5 KD did not change STZ/PA-induced gene expression of ER stress markers BiP and CHOP but significantly increased H2O2 production. This was associated with significantly elevated gene expression of mitochondrial SOD2, which converts superoxide into H2O2. Cytoplasmatic SOD1 and H2O2-decomposing catalase, PRDX1 and GPx1 remained unaffected. Conclusion: Increased circulating free fatty acids in obesity promote oxidative stress. Loss of ETV5 increases ROS production in mitochondria during cellular stress by PA and STZ, as indicated by upregulated SOD2 gene expression. This suggests a role for ETV5 in controlling mitochondrial oxidative stress in pancreatic β-cells. Disclosure X. Yi: None. G. Päth: None. J. Seufert: Advisory Panel; Abbott, Sanofi-Aventis Deutschland GmbH. Research Support; Boehringer Ingelheim International GmbH. Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. Funding XY is supported by China Scolarship Council (CSC) China,GP received Projektförderung from the German Diabetes Society (DDG)

Tigecycline Suppresses the Virulence Factors of Multidrug-Resistant Acinetobacter baumannii Allowing Human Neutrophils to Act.

PurposeTo determine the ability of human neutrophils to kill multidrug-resistant Acinetobacter baumannii (MDRAB) in the presence of tigecycline (TGC).MethodsClinical isolates of MDRAB were cultured with human neutrophils and H2O2 in the presence of TGC. The numbers of viable bacteria, catalase activity, gene expression at the K locus of the MDRAB, reactive oxygen species (ROS) production, and granule exocytosis in human neutrophils were determined.ResultsThere was a time-dependent increase in the numbers of MDRAB after co-culturing with human neutrophils, whereas there was a significant decrease in the MDRAB numbers when co-cultured with both, human neutrophils and TGC for 6 h. The presence or absence of TGC did not affect total ROS production or the expression of CD11b, CD15, and CD63 on human neutrophils occurred when co-cultured with MDRAB. TGC significantly suppressed catalase activity and gene expression at the K locus of MDRAB, and significantly reduced the thickness of the capsule. Additionally, the bacterial viability of TGC-treated MDRAB cultured with H2O2 was lower than that without H2O2 after 6 h of culture.ConclusionTGC significantly suppressed the expression of catalase and the capsule in MDRAB without adverse effects on neutrophil function, allowing human neutrophils to kill MDRAB. TGC is an effective antibiotic for treating MDRAB infections.

Mechanisms underlying salicylic acid on root parameters and antioxidant enzyme activity of potato plant under Lelliottia amnigena stress

Salicylic acid (SA) plays many roles in plant physiology. In addition to pathogenesis-related resistance, SA is involved in the response to biotic stress. There are no adequate studies on mechanism underlying SA-mitigated Lelliottia amnigena infestations in potato (Solanum tuberosum L.) plant. Therefore, this study evaluated the mechanisms of SA on antioxidant enzyme activity of potato plant roots under L. amnigena stress. The bacterial suspension (3.69 × 107 CFU mL-1) at 0.3 mL was inoculated into potato plants through stem injection. After 24 h, different SA concentrations (0.5, 1.0, 1.5 and 2.0 mM) were sprayed to the potato plants, and water as control. The results showed that L. amnigena infestation decreased fresh weight, dry weight, and relative water content of roots by 44.8%, 11.8% and 34.8%, respectively, compared to the control. The potato plant treatment with SA increased fresh weight, dry weight, and relative water content by an average of 34.88%, 10.28% and 13.50%; increased superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), polyphenol oxidase (PPO), and phenylalanine ammonia-lyase (PAL) by 35.95%, 32.55%, 33.74%, 33.25%, and 38.90%; decreased malondialdehyde (MDA) and hydrogen peroxide (H2O2) content in potato plant roots by 42.7% and 31.1%, respectively, under L. amnigena stress compared to control. Treatment with SA induced transcriptional levels of the SOD, POD, CAT and glutathione S-transferase (GST) gene expression across the four levels of SA by an average of 3.12-fold, 3.46-fold, 2.93-fold and 3.83-fold, respectively, compared to control. Salicylic acid increased antioxidant enzymes activity in roots of potato plant under L. amnigena stress.

Response of zebrafish to royal jelly supplementation and differences in stocking density

Dietary supplementation with royal jelly (RJ) may improve growth, antioxidant gene expression, and intestinal antioxidant capacity, and possibly mitigate effects of stress induced by high stocking density (HSD) in zebrafish (Danio rerio). Effects of HSD and RJ supplementation on growth performance, antioxidant gene expression, and intestinal antioxidant capacity in zebrafish were investigated. A total of 240 four-month-old zebrafish were used in a 2 x 2 factorial design, with four treatments and three replications. The treatments consisted of normal stocking density (NSD) (1 fish/L) and high stocking density (HSD) (3 fish/L) and an unsupplemented commercial diet (0RJ) and commercial diet supplemented with 10% RJ (10RJ). The experiment lasted 25 days. Daily weight gain, final body length, specific growth rate, and survival were recorded. On day 25, six fish per treatment were euthanised and their intestines analysed for antioxidant capacity, and superoxide dismutase 2 (SOD2) and catalase (CAT) gene expression. There were no effects of diet or SD and diet interaction on growth. High stocking density decreased daily weight gain by 25.31%, body length by 2.70%, and survival by 16.85%. Stocking density (SD) and diet interaction influenced intestinal SOD2 and CAT expression and antioxidant capacity. The HSD/0RJ group had lower antioxidant gene expression and antioxidant capacity than the HSD/10RJ and NSD/0RJ groups. Supplementation with RJ did not mitigate the harmful effects of stocking stress. These results indicate that HSD promotes transcriptional suppression of gene encoding enzymes that form the first line of antioxidant defence, resulting in reduced elimination of toxic substances and occurrence of intestinal oxidative stress.

Effect ofmelatonin onthe gastric antioxidant defence inexperimental burn trauma.

Severe burn trauma triggers oxidative gastric mucosal injury. The purpose ofthis study was toinvestigate the antioxidant defence mechanisms and protective effect ofmelatonin inthe gastric mucosa after burn injury. Inorder toinvestigate the mechanisms involved inthe gastric antioxidant defence inarat burn model, quantitative real-time PCR and immunohistochemistry techniques were applied. Ananalysis ofglutathione peroxidase4 (GPx4), glutathione reductase (GR), and catalase (Cat) gene expression was performed along with the evaluation ofthe gastric Cu/Zn superoxide dismutase (Cu/Zn SOD) activity. Melatonin was applied immediately and 12h after 30% oftotal body surface area burns. The burn injury significantly increased the Gpx4 mRNA (P<0.0001) and Gsr mRNA (P<0.0001) expression. Italso had aslight positive effect onthe Cat mRNA expression and Cu/Zn SOD activity. Melatonin, inturn, markedly augmented the burn-induced Cu/Zn SOD (P<0.0001) activity, reversed the Gpx4 mRNA (P<0.0001) and Gsr mRNA (P<0.0001) expression, and inhibited the Cat mRNA level. Inconclusion, the present study suggests that aburn injury adaptively increases the Cu/Zn SOD activity and enhances the Gpx4 and Gsr gene expression inthe gastric mucosa. Melatonin effectively modulates the expression ofthe cellular antioxidant enzymes, and improves the antioxidant defence byaugmenting the Cu/Zn SOD activity.

Betaine Regulates the Production of Reactive Oxygen Species Through Wnt10b Signaling in the Liver of Zebrafish.

When fish are under oxidative stress, levels of reactive oxygen species (ROS) are chronically elevated, which play a crucial role in fish innate immunity. In the present study, the mechanism by which betaine regulates ROS production via Wnt10b/β-catenin signaling was investigated in zebrafish liver. Our results showed that betaine enrichment of diet at 0.1, 0.2 and 0.4 g/kg induced Wnt10b and β-catenin gene expression, but suppressed GSK-3β expression in zebrafish liver. In addition, the content of superoxide anion (O2 ·−), hydrogen peroxide (H2O2) and hydroxyl radical (·OH) was decreased by all of the experimental betaine treatments. However, betaine enrichment of diet at 0.1, 0.2 and 0.4 g/kg enhanced gene expression and activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) in zebrafish liver. In addition, Wnt10b RNA was further interfered in zebrafish, and the results of Wnt10b RNAi indicated that Wnt10b plays a key role in regulating ROS production and antioxidant enzyme activity. In conclusion, betaine can inhibit ROS production in zebrafish liver through the Wnt10b/β-catenin signaling pathway.

Oxidative stress and gene expression of antioxidants enzymes in monocrotaline-induced pulmonary hypertension following the administration of antiretroviral medications in rats

Objectives: Pulmonary hypertension (PH) is a severe life-threatening pulmonary vasculopathy. This study investigated the effects of zidovudine (AZT) and/or ritonavir (RTV) in the oxidative process of monocrotaline (MCT)-induced PH in rats. Materials and Methods: Forty male Sprague-Dawley rats weighing between 200 and 250 g were randomized into five different groups (n = 8 per group). A single dose intraperitoneal injection of MCT (60 mg/kg) was administered to all the rats in four of the groups. Daily oral administration of the antiretroviral (ARV) medications – (1) AZT-only (100 mg/kg); (2) RTV only (30 mg/kg); (3) AZT+ RTV (100+30 mg/kg); and (4) the untreated group had equivalent volume of saline for 28 days, respectively, while the (5) control group had neither MCT nor ARV. Gene expression using RT-PCR for the antioxidants and laboratory assay for lipid peroxidation was analyzed. Results: A significantly higher mRNA gene expression of catalase, superoxide dismutase and glutathione peroxidase in the treated rats was observed compared to the untreated. There was an increase in malondialdehyde (MDA) in the heart tissues of untreated rats (37.01 ± 1.16 nmol/g, P &lt; 0.0001) compared to the control group (3.46 ± 0.97 nmol/g) with an associated reduction in MDA by the ARVs. Furthermore, an increase in the total antioxidant capacity in AZT (0.85 ± 0.02 nmol/g, P &lt; 0.0001), RTV (0.63 ± 0.03 nmol/g, P &lt; 0.0001), and combination of AZT/RTV (0.77 ± 0.06 nmol/g, P &lt; 0.0001) compared to untreated (0.28 ± 0.03) rats. Conclusion: AZT and RTV ameliorate PH in experimental rats. This study demonstrated that MCT-induced PH generates ROS in rats and the protective role of ARV drugs in the treatment of PH.

Effects of a Short-Term Lipopolysaccharides Challenge on Mouse Brain and Liver Peroxisomal Antioxidant and β-oxidative Functions: Protective Action of Argan Oil.

During sepsis, the imbalance between oxidative insult and body antioxidant response causes the dysfunction of organs, including the brain and liver. Exposing mice to bacterial lipopolysaccharides (LPS) results in a similar pathophysiological outcome. The protection offered by argan oil was studied against LPS-induced oxidative stress, dysregulation of peroxisomal antioxidants, and β-oxidation activities in the brain and liver. In a short-term LPS treatment, lipid peroxidation (malonaldehyde assay) increased in the brain and liver with upregulations of proinflammatory tumor necrosis factor (Tnf)-α and anti-inflammatory interleukin (Il)-10 genes, especially in the liver. Although exposure to olive oil (OO), colza oil (CO), and argan oil (AO) prevented LPS-induced lipid peroxidation in the brain and liver, only AO exposure protected against liver inflammation. Remarkably, only exposure to AO prevented LPS-dependent glutathione (GSH) dysregulation in the brain and liver. Furthermore, exposure to AO increased more efficiently than OO and CO in both organs, peroxisomal antioxidant capacity via induction of catalase (Cat) gene, protein and activity expression levels, and superoxide dismutase (Sod1) mRNA and activity levels. Interestingly, LPS decreased protein levels of the peroxisomal fatty acid-ATP binding cassette (ABC) transporters, ABCD1 and ABCD2, and increased acyl-CoA oxidase 1 (ACOX1) protein expression. Moreover, these LPS effects were attenuated for ABCD1 and ACOX1 in the brain of mice pretreated with AO. Our data collectively highlight the protective effects of AO against early oxidative stress caused by LPS in the brain and liver and their reliance on the preservation of peroxisomal functions, including antioxidant and β-oxidation activities, making AO a promising candidate for the prevention and management of sepsis.

Combined administration routes of marine yeasts enhanced immune-related genes and protection of white shrimp (Penaeus vannamei) against Vibrio parahaemolyticus

Antibiotic usage to control infectious diseases in shrimp aquaculture has led to serious problems on antimicrobial resistance. An alternative to mitigate this issue is the use of probiotics, which can be easily administered by feed and water. This study examines immunomodulatory and protective effects of the marine yeasts Debaryomyces hansenii CBS8339 (Dh) and Yarrowia lipolytica Yl-N6 (Yl) -alone and mixed-in white shrimp Penaeus vannamei post-larvae. Administration routes (fed and water alone or in combination), supplementation frequency and time elapsed after the last dietary supplement were tested on growth and gene expression of penaeidin, lectin, lysozyme, superoxide dismutase, catalase, and peroxidase, as well as survival upon Vibrio parahaemolyticus IPNGS16 challenge. Penaeidin and lectin genes were upregulated in post-larvae fed orally with Yl or combined Dh + Yl. Higher growth and survival for yeast supplementation treatments were observed compared to the control group, mainly when yeasts (Dh + Yl) and administration routes (feed and water) were combined. In conclusion, mixed yeast and combined administration routes improved growth and immunity against V. parahaemolyticus.

Use of the β-Glucan-Producing Lactic Acid Bacteria Strains Levilactobacillus brevis and Pediococcus claussenii for Sourdough Fermentation-Chemical Characterization and Chemopreventive Potential of In Situ-Enriched Wheat and Rye Sourdoughs and Breads.

The aim of the present study was to examine β-glucan production and the potential prebiotic and chemopreventive effects of wheat and rye sourdoughs and breads generated with wild-type and non-β-glucan-forming isogenic mutant strains of Levilactobacillus brevis and Pediococcus claussenii. Sourdough and bread samples were subjected to in vitro digestion and fermentation. Fermentation supernatants (FS) and pellets (FP) were analyzed (pH values, short-chain fatty acids (SCFA), ammonia, bacterial taxa) and the effects of FS on LT97 colon adenoma cell growth, viability, caspase-2 and -3 activity, genotoxic and antigenotoxic effects and on gene and protein expression of p21, cyclin D2, catalase and superoxide dismutase 2 (SOD2) were examined. Concentrations of SCFA were increased and concentrations of ammonia were partly reduced in the FS. The relative abundance of Bifidobacteriaceae was increased in all FPs. Treatment with FS reduced the growth and viability of LT97 cells and significantly increased caspase-2 and -3 activities without exhibiting genotoxic or antigenotoxic effects. The p21 mRNA and protein levels were increased while that of cyclin D2 was reduced. Catalase and SOD2 mRNA and protein expression were marginally induced. The presented results indicate a comparable chemopreventive potential of wheat and rye sourdoughs and breads without an additional effect of the formed β-glucan.

Angiotensin II Promotes Skeletal Muscle Angiogenesis Induced by Volume-Dependent Aerobic Exercise Training: Effects on miRNAs-27a/b and Oxidant-Antioxidant Balance.

Aerobic exercise training (ET) produces beneficial adaptations in skeletal muscles, including angiogenesis. The renin–angiotensin system (RAS) is highly involved in angiogenesis stimuli. However, the molecular mechanisms underlying capillary growth in skeletal muscle induced by aerobic ET are not completely understood. This study aimed to investigate the effects of volume-dependent aerobic ET on skeletal muscle angiogenesis involving the expression of miRNAs-27a and 27b on RAS and oxidant–antioxidant balance. Eight-week-old female Wistar rats were divided into three groups: sedentary control (SC), trained protocol 1 (P1), and trained protocol 2 (P2). P1 consisted of 60 min/day of swimming, 5×/week, for 10 weeks. P2 consisted of the same protocol as P1 until the 8th week, but in the 9th week, rats trained 2×/day, and in the 10th week, trained 3×/day. Angiogenesis and molecular analyses were performed in soleus muscle samples. Furthermore, to establish ET-induced angiogenesis through RAS, animals were treated with an AT1 receptor blocker (losartan). Aerobic ET promoted higher VO2 peak and exercise tolerance values. In contrast, miRNA-27a and -27b levels were reduced in both trained groups, compared with the SC group. This was in parallel with an increase in the ACE1/Ang II/VEGF axis, which led to a higher capillary-to-fiber ratio. Moreover, aerobic ET induced an antioxidant profile increasing skeletal muscle SOD2 and catalase gene expression, which was accompanied by high nitrite levels and reduced nitrotyrosine concentrations in the circulation. Additionally, losartan treatment partially re-established the miRNAs expression and the capillary-to-fiber ratio in the trained groups. In summary, aerobic ET promoted angiogenesis through the miRNA-27a/b–ACE1/Ang II/VEGF axis and improved the redox balance. Losartan treatment demonstrates the participation of RAS in ET-induced vascular growth. miRNAs and RAS components are promising potential targets to modulate angiogenesis for combating vascular diseases, as well as potential biomarkers to monitor training interventions and physical performance.

New insights into arsenic, lead, and iron neurotoxicity: Activation of MAPK signaling pathway and oxidative stress.

Toxic metals cause neurodegeneration via formation of toxic complexes with the cellular compounds and production of highly reactive oxygen species. The present study aimed to investigate the role of mitogen-activated protein kinase (MAPK) signaling pathway in iron, lead, and arsenic induced neurotoxicity. Also, to explore their effect on brain enzymes, inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF-κB) in rat brains. Rats were divided into four groups (n = 8): Control group, lead group (30 mg/kg lead acetate), arsenic group (5 mg/kg sodium arsenite), and iron group (100 mg/kg ferric hydroxide). Treatments were given three times/week orally for 2 months. Brain tissues were assessed for reduced glutathione and malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), alkaline phosphatase (ALP), acid phosphatase (ACP), Na+ /K+ activated adenosine 5'-triphosphatase (Na+ /K+ -ATPase)and acetylcholinesterase (AChE) activities, expression of iNOS and NF-κB, and Western blot analysis of c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) proteins. Levels of arsenic, iron, and lead were significantly (p = 0.000) increased in blood and brain tissues. Levels of MDA, SOD, CAT, iNOS, and NF-κB gene expression, phosphorylated JNK and phosphorylated ERK proteins were increased significantly in lead, arsenic, and iron treated rat groups compared to control. ALP, ACP, AChE, and ATPase activities in brain were significantly altered in metal-treated rat groups compared to control. Iron, lead, and arsenic induced neurotoxicity activated the pro-inflammatory mediators NF-κB, iNOS, and MAPK pathway and altered the activity of brain ALP, ACP, Na+ /K+ -ATPase, CAT, SOD, and AChE.

Ingestion Effect of Polyethylene Terephthalate (PET) Nanoparticles on Juveniles of Shrimp &lt;i&gt;Litopenaeus vannamei&lt;/i&gt;

Polyethylene terephthalate (PET) is among the major plastics produced, and thus the PET nanoparticles are distributed worldwide in marine systems. In this work, the effects of PET nanoparticles (NanoPET) in the shrimp feed were determined in juveniles of shrimp Litopenaeus vannamei. No significant changes in the concentrations of triglycerides and cholesterol in hemolymph were detected. A slight but not significantly higher nitrites content in the shrimp hepatopancreas was detected when the NanoPET concentration in the feed was increased, while a significant higher ROS generation was detected at high NanoPET concentration. This increase in ROS generation matched with the increase of gene expression of antioxidative proteins catalase, superoxide dismutase, and glutathione peroxidase, while glutathione transferase was not affected. Thus, these increased levels of antioxidant enzymes in shrimps exposed to NanoPET seem to be a protection response by the generation of free radicals induced by the presence of nanoplastic.

Early Effects of Extracellular Vesicles Secreted by Adipose Tissue Mesenchymal Cells in Renal Ischemia Followed by Reperfusion: Mechanisms Rely on a Decrease in Mitochondrial Anion Superoxide Production.

Acute kidney injury (AKI) caused by ischemia followed by reperfusion (I/R) is characterized by intense anion superoxide (O2•−) production and oxidative damage. We investigated whether extracellular vesicles secreted by adipose tissue mesenchymal cells (EVs) administered during reperfusion can suppress the exacerbated mitochondrial O2•− formation after I/R. We used Wistar rats subjected to bilateral renal arterial clamping (30 min) followed by 24 h of reperfusion. The animals received EVs (I/R + EVs group) or saline (I/R group) in the kidney subcapsular space. The third group consisted of false-operated rats (SHAM). Mitochondria were isolated from proximal tubule cells and used immediately. Amplex Red™ was used to measure mitochondrial O2•− formation and MitoTracker™ Orange to evaluate inner mitochondrial membrane potential (Δψ). In vitro studies were carried out on human renal proximal tubular cells (HK-2) co-cultured or not with EVs under hypoxic conditions. Administration of EVs restored O2•− formation to SHAM levels in all mitochondrial functional conditions. The gene expression of catalase and superoxide dismutase-1 remained unmodified; transcription of heme oxygenase-1 (HO-1) was upregulated. The co-cultures of HK-2 cells with EVs revealed an intense decrease in apoptosis. We conclude that the mechanisms by which EVs favor long-term recovery of renal structures and functions after I/R rely on a decrease of mitochondrial O2•− formation with the aid of the upregulated antioxidant HO-1/Nuclear factor erythroid 2-related factor 2 system, thus opening new vistas for the treatment of AKI.

Local treatment with Sema3a could promote the osseointegration of hydroxyapatite coated titanium rod in diabetic rats.

Recently, semaphorin 3A (Sema3A) has been identified as a critical gene for osteogenic differentiation of mesenchymal stem cells and increases osteoblastic bone formation. However, in current research studies, there is a lack of focus on whether Sema3a can affect the osseointegration of titanium rods in diabetes and through what biological mechanisms. Therefore, the present work was aimed to evaluate the effect of local administration with Sema3A on hydroxyapatite coated titanium rod osseointegration in diabetic rat model and preliminary exploration of possible mechanisms. The MC3T3-E1 cells were co-cultured with Sema3A and high glucose and induced to osteogenesis, and the cell viability, osteogenic activity was observed by Cell Counting Kit-8(CCK-8), Alkaline Phosphatase staining, Alizarin Red Staining, and Western Blot. In vitro experiments, CCK-8, ALP, and ARS staining results show that the mineralization and osteogenic activity of MC3T3-E1increased significantly after intervention by Sema3A, as well as a higher levels of protein expressions including Runt-Related Transcription Factor 2, silent mating type information regulation 2 homolog-1(SIRT1), catalase (CAT), superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2). In vivo experiment, a better stability and osseointegration of the titanium rod were observed after treatment with Sema3A, as well as a higher SOD1, SOD2, CAT, and SIRT1 gene expression. The present study indicates that local treatment with Sema3A was associated with increased osseointegration of titanium rod by reducing the oxidative stress of osteoblasts and enhancing the function of osteoblasts in a diabetic rat.

Dietary red macroalgae (Halopithys incurva) improved systemic an mucosal immune and antioxidant parameters and modulated related gene expression in zebrafish (Danio rerio)

In the present study, the effects of dietary Halopithys incurva, a red macroalgae species, (0.25, 0.50, 1%) on whole-body serum and skin mucus immune system, antioxidant system and expression of various genes in zebrafish were investigated. At the end of the 8-week study, total protein, total immunoglobulin and lysozyme activities in whole-body serum and skin mucus increased in fish fed H. incurva (P < 0.05). While an increase was observed in superoxide dismutase (SOD), Catalase (CAT) and glutathione peroxidase (GPx) which are antioxidant enzyme activities in whole-body serum and skin mucus, a decrease in malondialdehyde (MDA) levels was detected (P < 0.05). All of the immune-related genes examined, such as Interleukin-1 beta (IL-1β), Tumor necrosis factor-alpha (TNF-α), Interferon-gamma (INF- γ), were upregulated by the addition of 0.5% H. incurva (P < 0.05). While SOD and GPx, which are antioxidant enzyme-related genes, were remarkably upregulated in macroalgae fed fish (P < 0.05), no change was observed in CAT gene expression (P > 0.05). Based on the results of this study, it is considered that the addition of 0.5% H. incurva to the diets of commercially farmed fish will increase their immune and antioxidant defences and may contribute to the aquaculture sector for more sustainability.

Neuroprotective effects of Tongtian oral liquid, a Traditional Chinese Medicine in the Parkinson's disease-induced zebrafish model

Traditional Chinese medicine (TCM) is used in the treatment of Parkinson’s disease (PD) worldwide. Tongtian Oral Liquid (TTKFY) is one such patented TCM, and a poly-herbal formulation, composed of 11 herbal constituents, which possess neuroprotective, antioxidant, pain-relieving properties. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP), a neurotoxicant is used to induce PD in animal models. The present study was aimed to evaluate the neuroprotective effects of TTKFY, on dopaminergic neuron development, antioxidant activities, and gene expression involved in the dopaminergic pathway in the MPTP-treated zebrafish model. Zebrafish larvae were treated with MPTP (70 μM) to induce PD and then by different concentrations (0.5, 1, 2, 4 ml/L) of TTKFY. Transgenic zebrafish Vmat: GFP at 5 dpf were used to observe the development of dopaminergic neurons. The activities of T-Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malonaldehyde (MDA) and mRNA gene expression of dopamine pathway were quantified. MPTP-treated zebrafish larvae showed degeneration of dopaminergic neurons, locomotion dysfunction, diminished activities of antioxidant enzymes, MDA accumulation, and altered gene expression of dopamine pathway. In contrast, TTKFY protected dopaminergic neurons, ameliorated behavioral impairments, antioxidant activities and mRNA gene expression of dopamine pathway in a dose-dependent manner. Thus, TTKFY confers protective effects against MPTP-induced neurotoxicity and the mechanisms of protection may be related to the recovery of dopaminergic neurons by reducing oxidative stress via restoring cellular defense mechanisms and thereby highlighting its therapeutic potential to prevent the progression of PD. Further studies are necessary to elucidate the mechanism of action of TTKFY on neuroprotection in the MPTP-induced PD model.