Superoxide Dismutase Gene Expression Research Articles

Sitagliptin inhibits lipopolysaccharide-induced inflammatory response in human gingival fibroblasts by blocking nuclear factor-κB signaling pathway

This study was performed to clarify the effects of sitagliptin on Porphyromonas gingivalis-lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs), explore the molecular mechanism of its roles, and provide a foundation for clinical therapeutics in periodontitis. Healthy gingival samples were collected from the donors. HGFs were isolated with enzymic digestion method and identified. The effects of LPS and sitagliptin on cell viability were detected by cell-counting kit-8 (CCK8). The mRNA levels of inflammatory cytokines, namely, interleukin (IL)-6, IL-8, C-C motif ligand 2 (CCL2), and superoxide dismutase 2 (SOD2), were evaluated by quantity real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA) was used to measure the secretion protein levels of IL-6, IL-8, and CCL2. Western blot analysis was used to further investigate the activation of nuclear factor (NF)-κB signaling pathway. The effect of NF-κB pathway inhibitor BAY11-7082 on LPS-induced HGF inflammatory cytokines at the gene level was verified by qRT-PCR. Low concentrations of sitagliptin (0.1, 0.25, and 0.5 µmol·L-1) did not affect HGF growth in 24 and 48 h, whereas high concentrations of sitagliptin (5-1 000 µmol·L-1) significantly inhibited cell proliferation. Sitagliptin suppressed 5 µg·mL-1 of LPS-induced IL-6, IL-8, CCL2, and SOD2 gene expression levels in HGF in a concentration-dependent manner. Furthermore, sitagliptin significantly decreased the elevated secretion of IL-6, IL-8, and CCL2 protein induced by LPS. Western blot analysis showed that 0.5 µmol·L-1 of sitagliptin significantly inhibited LPS-induced NF-κB signaling pathway activation. Results of qRT-PCR analysis indicated that 0.5 µmol·L-1 of sitagliptin and 5 µmol·L-1 of BAY11-7082 significantly inhibited LPS-induced IL-6, IL-8, CCL2, and SOD2 gene expressions. Sitagliptin could significantly inhibit LPS-induced HGF inflammatory response by blocking the NF-κB signaling pathway activation.

Silicon- induced nitric oxide burst modulates systemic defensive responses of Salvia officinalis under copper toxicity

In this study, the role of nitric oxide (NO) burst in modulating Si-induced defensive responses in leaves and roots of Salvia officinalis under copper (Cu) stress were investigated. The result showed that 400 μM Cu markedly reduced shoot dry weight, but increased electrolyte leakage (EL) in leaves and both Si and sodium nitroprusside (SNP as the NO donor) improved these attributes in a dose-dependent manner. Interestingly, Cu toxicity systemically boosted a NO burst in both roots and shoots and applying Si and SNP markedly intensified it. The application of Si and SNP alone as well as their combination improved growth parameters and systemically alleviated Cu-induced lipid peroxidation and H2O2 accumulation through lowering Cu accumulation, increasing proline content, enhancing the activities of catalase (CAT) and superoxide dismutase (SOD) in both roots and leaves and up-regulating expression of SOD gene in leaves of S. officinalis. NO generation was substantially arrested and the responses induced by Si were significantly suppressed by pretreatment with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy l-3-oxide (cPTIO) as a NO scavenger, Nx-Nitro- L-arginine methyl ester hydrochloride (L-NAME) as a nitric oxide synthase inhibitor, and tungstate as a nitrate reductase inhibitor. These novel results indicate that Si can induce Cu tolerance through triggering NO generation which systemically modulates defensive reactions in both roots and leaves of Salvia officinalis.

Study on the mechanism of exogenous serotonin improving cold tolerance of rapeseed (Brassica napus L.) seedlings

Cold stress disturbs numerous physiological and biochemical processes, restricting plant growth and productivity. In the current study, the protective role of exogenous serotonin in alleviating cold stress was investigated in rapeseed (Brassica napus L.) seedlings. The rapeseed seedlings were pretreated with different concentrations (0, 0.01, 0.02, 0.03, and 0.04 g L− 1) of serotonin solution and then were exposed to cold stress (4, 2, 0, and − 2 °C). The results indicated that the pretreatment of serotonin significantly increased the survival rate. Mainly, 0.03 g L− 1 of serotonin increased the survival rate by 75% compared to control conditions. The physiological and biochemical indexes and the expression of cold tolerance-related genes were analyzed in the seedlings pretreated with 0.03 g L− 1 of serotonin. The contents of proline (PRO), soluble sugar (SS), and soluble protein (SP); and the activities of antioxidant defense such as catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) were significantly increased by exogenous serotonin under cold stress. Supplemented serotonin significantly increased the expression of SOD, COR6.6, COR15, and CBFs genes under cold stress.Overall, our results indicate that the optimal concentration (0.03 g L− 1) of exogenous serotonin maintained the osmotic potential balance in cells under cold stress by increasing the content of osmotic regulatory substances (SS, SP, and PRO), improving the scavenging ability of reactive oxygen species (ROS), increasing the antioxidant enzyme activities (CAT, POD, and SOD) and the transcriptional level of cold stress-related genes, helping rapeseed seedlings to cope with the cold stress. Therefore, serotonin-induced regulatory interactions between physiological and biochemical processes and the elevated expression of stress-associated genes may be a beneficial technique for cold stress tolerance in plants.

Genome-wide identification of the SOD gene family and expression analysis under drought and salt stress in barley

Superoxide dismutase (SOD) plays a vital role in the removal of active oxygen in plant. In this study, bioinformatics research and expression analysis of SOD gene family under drought and salt stress has been done in barley (Hordeum vulgare L., Hv). Seven SOD genes were identified, including four Cu/Zn-SODs, two Fe-SODs and one Mn-SOD. Those three kinds of SOD genes were distributed in 2, 4 and 7 chromosomes, respectively. Phylogenetic analysis revealed that SODs of barley, rice and Arabidopsis thaliana can be divided into three subfamilies (A–C). Motif analysis founded six conservative motifs. Most SOD genes had relatively conservative intron/exon and motif composition, but the number of intron/exons varied greatly among different genes. Based on RNA-seq data and qRT-PCR analysis of expression changes of barley SOD family gene under stress, HvCSD1, HvCSD4 and HvFSD1 were more valuable for in-depth research due to their significant changes in their expression after stress treatment. These outcomes help to lay the foundation for studying the gene function of barley SOD family and provide the improvement of drought and salt tolerance barley genetic breeding.

The cultivar-dependent high oxidation resistance might be the indicator for Cd pollution-safe cultivars (Cd-PSCs) in leafy vegetables

The Cd accumulating difference in edible parts of leafy vegetables were involvement with the cultivar-dependent oxidation resistance of plants. According to the transcriptomic results, the total expression of the 4 major antioxidase genes in Cd pollution-safe cultivars (Cd-PSCs) under control condition were higher than in high-Cd-accumulating cultivars (HCCs) of the 4 tested leafy vegetables, indicating the cultivar-dependent high oxidation resistance of Cd-PSCs. Simultaneously, expression of superoxide dismutase (SOD) and peroxidase (POD) genes in Cd-PSCs were all higher than in HCCs under control condition. The real detection of SOD activities in Cd-PSCs under control condition were higher than in HCCs, which verified the transcriptomic results. What’s more, there were no uniform response mechanisms of antioxidase genes to cope with Cd stress among the 4 tested leafy vegetables, even 3 of them were native from the same genus Brassica. Meanwhile, expression of the 4 major antioxidase genes were difference from genus, such as the polyphenol oxidase (PPO) genes were hardly expression in genus Brassica. These results would contribute to the understanding the inherent difference between Cd-PSCs and HCCs, and the cultivar-dependent Cd oxidation resistance related to Cd-PSCs might a easy signal for in vitro catching and screening.

Iron oxide nanoparticles conjugated curcumin to promote high therapeutic efficacy of curcumin against hepatocellular carcinoma

BackgroundCurcumin’s excellent conjugation capability with iron oxide nanoparticles plays a crucial role in enhancing both properties. Iron oxide, as a nanocarrier, will improve curcumin anticancer activity, while curcumin, as a capping agent, will minimize iron oxide nanoparticles toxicity and optimize their biomedical use. MethodologyCytotoxic and antioxidant effects of free curcumin (free Cur) and curcumin capped iron oxide nanoparticles (IONs@Cur) against human liver cancer cells (HepG2) were investigated in vitro. The genomic effect of free Cur and IONs@Cur on the expression of tumor suppressor gene (TP53), autophagy 4 (ATG-4), and superoxide dismutase (SOD2) genes were assessed using quantitative PCR (qPCR). ResultsIONs@Cur results showed significant cytotoxic effects against HepG2 cells, compared with free Cur, and the measured total antioxidant capacity (TAC) for HepG2 cells treated with IONs@Cur was superior to free Cur. Additionally, the treatment with IONs@Cur significantly upregulated the gene expression levels of SOD2 and TP53. Remarkably, the immunofluorescence staining of ATG-4 demonstrated that curcumin conjugation with IONs potentiated the cancer killing effect of curcumin via inducing autophagy. ConclusionThe promising iron oxide nanocarrier would greatly enhance curcumin anticancer activities against HepG2 cells.

Modulatory effect of fructooligosaccharide against triphenyltin-induced oxidative stress and immune suppression in goldfish (Carassius auratus)

Triphenyltin (TPT) is a widely used pesticide that is highly toxic to a variety of organisms, including humans, and is a potential contributor to environmental pollution. The present study was conducted to evaluate the oxidative stress and immunotoxicity induced by TPT in goldfish (Carassius auratus) and the protective effects of fructooligosaccharide (FOS). Goldfish (mean weight of 13.3 ± 0.2 g) were randomly divided into six groups with three replicates: (G1) the control group, (G2) the 10 ng/L TPT group, (G3) the 0.4% FOS group, (G4) the 10 ng/L TPT + 0.4% FOS group, (G5) the 0.8% FOS group, and (G6) the 10 ng/L TPT + 0.8% FOS group. The results showed that 10 ng/L TPT induced oxidative stress and significantly decreased the activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), in the liver and the gene expression of SOD, GPx, metallothionein (MT), and peroxiredoxin-4 (Prdx-4). The concentration of malondialdehyde (MDA) and the gene expression of cytochrome P450 (CYP) and glutathione S-transferase (GST) in the liver were significantly increased in the TPT-treated group. Exposure to 10 ng/L TPT in water induced immune suppression and significantly decreased the activities of immune enzymes, such as lysozyme, myeloperoxidase (MPO), alternative complement (ACH50), acid phosphatase (ACP) and alkaline phosphatase (AKP), in the serum. TPT could stimulate the fish to generate large amounts of proinflammatory cytokines, including increased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and nitric oxide (NO) levels and TNF-α, IL-6, IL-1β, and NF-κB mRNA expression. However, TPT-induced toxicity was significantly ameliorated in the groups treated with FOS, and FOS partly prevented alterations in the activities of antioxidant enzymes and the expression of antioxidant- and ROS scavenger-related genes. In addition, TPT-induced immune toxicity was significantly ameliorated in the groups treated with FOS. FOS markedly suppressed TNF-α, IL-6, IL-1β, and NO production and TNF-α, IL-6, and IL-1β mRNA expression in the TPT-treated groups. The study indicated that TPT-induced oxidative stress may play a critical role in inhibiting immunity. However, FOS administration attenuates TPT-induced oxidative stress and immune suppression in goldfish.

D-limonene in diabetic rats

Introduction: Diabetes mellitus (DM) is a multi-factorial condition associated with oxidative stress. Limonene, as a plant-derived antioxidant, can be used for treating DM. Objectives: An investigation on antioxidant effects in diabetic rats exposed to D-limonene. Materials and Methods: Sixty male Wistar rats were categorized into six groups as follows: control (healthy rats), diabetic control (untreated diabetic rats), sham glibenclamide, diabetic glibenclamide, sham limonene, and finally diabetic limonene. Alloxan (100 mg/dL) was infused intraperitoneally to induce type 1 diabetes in rats. Rats in certain groups were given limonene (100 mg/dL) and glibenclamide (10 mg/dL) orally for 8 weeks. Subsequently, animals were killed, and their kidneys were removed. Serum levels of biochemical factors (including serum creatinine, urea, and glucose) were determined, and factors such as nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO) were measured in kidney tissue homogenate. The gene expression and enzymatic activity of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in the kidney were measured by real-time polymerase chain reaction (real-time PCR) and spectrophotometry, respectively. Results: Limonene treatment significantly decreased serum glucose, creatinine, and urea. Additionally, MDA, MPO, and NO significantly decreased while GSH increased after treatment with limonene. Real-time RT-PCR showed significant elevation (P<0.05) in mRNA levels of GPx, CAT, and SOD in the limonene-treated compared with the diabetic control group. Conclusion: Our results demonstrated that limonene as an herbal antioxidant had better effects on antioxidant markers compared to glibenclamide in rat models of diabetes.

The effects of pomegranate peel extract on the gene expressions of antioxidant enzymes in a rat model of alloxan-induced diabetes

This study was conducted to evaluate the anti-diabetic and antioxidant effects of hydroalcoholic pomegranate peel extract (APE) in alloxan-induced diabetes rat models. We divided 60 rats into the following six equal groups (n = 10): Healthy control; diabetic control (100 mg/kg alloxan); sham + glibenclamide (10 mg/kg); diabetic + glibenclamide (10 mg/kg); sham + APE (200 mg/kg) and diabetic + APE (200 mg/kg). After 8 weeks, kidneys were taken out for biochemical and molecular studies. Following APE treatment, biochemical parameters including malondialdehyde (MDA), and glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) significantly induced in the treated group as compared with the control group (p < 0.05). Also, gene expression of GPx (3-fold), CAT (2.6-fold), and SOD (1.5-fold) were increased as compared to controls (p < 0.05). Overall, our results indicated that pomegranate can be used as an antioxidant agent to reduce complications from diseases associated with oxidative stress.

Exogenous phytosulfokine α (PSKα) application delays senescence and relieves decay in strawberry fruit during cold storage by triggering extracellular ATP signaling and improving ROS scavenging system activity

During postharvest life, strawberry fruit as a perishable commodity exhibiting short shelf life suffers from fungal decay that severely limits its marketability and nutritional value. Herein, we investigated the mechanisms activated by exogenous phytosulfokine α (PSKα) application at 150 nM to delay senescence and relieve decay in strawberry fruit during storage at 4 °C for 18 days. Our results showed higher extracellular adenosine triphosphate (ATP) accumulation arising from lower apyrase 1 (APY1) gene expression in strawberry fruit treated with 150 nM PSKα during storage at 4 °C for 6 days may serve as a signaling molecule to promote NADPH oxidase activity to trigger signaling H2O2 accumulation giving rise to higher SUMO E3 ligase (SIZ1) gene expression during 18 days of storage at 4 °C. Also, higher superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) genes expression and enzymes activity associated with higher methionine sulfoxide reductase (MSR) and peroxiredoxin (Prx) genes expression in strawberry fruit treated with 150 nM PSKα during storage at 4 °C for 18 days may be ascribed to extracellular ATP signaling. As a result, promoting ROS scavenging systems activity by triggering extracellular ATP signaling in strawberry fruit treated with 150 nM PSKα may be responsible for higher maintenance of membrane integrity as shown by lower malondialdehyde (MDA) accumulation during 18 days of storage at 4 °C. Besides, strawberry fruits treated with 150 nM PSKα exhibited lower weight loss, total soluble solids, and chroma value concurrent with higher firmness, titrable acidity, L* value, and hue angle as quality attributes, which indicated delayed fruit senescence. Based on our findings, exogenous PSKα application unveils its potential to be used as a promising signaling biopeptide for senescence delay and decay alleviation in strawberry fruit during its postharvest life.

Activation of liver X receptors ameliorates alterations in testicular function in rats exposed to electromagnetic radiation

ABSTRACT Introduction: Cell phones are essential for modern life and their usage becomes prevalent. Worries have increased concerning the harmful effects of their radio-frequency electromagnetic radiation. Liver X receptors (LXRs) are ligand-dependent transcription factors that have important roles in lipid metabolism and inflammation, plus several recently emerging roles. Whether it is useful to overcome the hazardous effects of cell phone radiation needs to be clarified. So, this study aimed to investigate the effect of LXRs activation on testicular changes in rats exposed to electromagnetic radiation. Methods: Thirty adult male Wistar rats were subdivided into control group, experimental group: exposed to cell phone electromagnetic radiation, and treated group: as experimental group and received LXRs agonist T0901317. Serum testosterone (T), Follicle-Stimulating Hormone (FSH), and Luteinizing Hormone (LH), testicular tissue malondialdehyde (MDA) and superoxide dismutase (SOD), and gene expressions of inflammatory and apoptotic markers were assessed. Seminal analysis and testicular histological examination were performed. Results: LXRs activation in rats exposed to cell phone radiation improved the decreased testicular and gonadotrophic hormones, semen quality parameters, tissue SOD, and anti-apoptotic gene expression as well as the elevated tissue MDA, apoptotic and inflammatory gene expressions, and the testicular histological changes induced by exposure to electromagnetic radiation. Conclusion: Exposure to cell phone radiation leads to harmful effects on spermatogenesis and LXRs activation could improve these effects via antioxidant, anti-inflammatory properties in addition to its endocrinal action.

The protective effects of red beetroot (Beta vulgaris l.) against oxidative stress in rats induced by high fat and fructose diet

Background: One of consequence high-fat and fructose diet is oxidative stress. Consumption of antioxidants from red beetroot may increase antioxidant defense.&#x0D; Objectives: This study aimed to evaluate red beetroot administration on improving antioxidant defense in rats induced high fat and fructose diet.&#x0D; Methods: A total 20 male Wistar rats were divided into 4 groups: 1) normal control group (N), received standard diet; 2) High fat and fructose diet (HF), received high fat and fructose diet (HFFD); 8 weeks induction with HFFD and received 9g red beetroot (BA); and combination of HFFD and 9g of red beetroot from beginning of the study (HFBA). At the end of the study the levels of circulatory oxidized LDL (ox-LDL) were determined using enzyme-linked immunosorbent assay (ELISA) method. Superoxide dismutase 2 (SOD2) and catalase (CAT) gene expressions were determined by quantitative polymerase chain reaction (qPCR) method.&#x0D; Results: Induction HFFD increased the levels of circulatory ox-LDL levels compared to normal control (10.00±0.29 vs 12.69±0.57). Administration of red beetroot for 6 weeks and combination HFFD with red beetroot during the study significantly decreased ox-LDL levels compared to high fat and fructose group (12.69±0.57 vs 9.66±0.46) and (12.69±0.57 vs 8.59±0.18), respectively. The decreased circulatory ox-LDL levels were found negatively correlated with upregulation SOD2 (r=-0.548; P=0.012) and CAT (r=-0.460; P=0.041) gene expression in the liver tissues.&#x0D; Conclusion: Administration of red beetroot may ameliorate oxidative stress in rats induced high-fat and fructose diet through increasing antioxidant defense.

Garlic Alleviates the Injurious Impact of Cyclosporine-A in Male Rats through Modulation of Fibrogenic and Steroidogenic Genes.

Simple SummaryThe use of garlic extract is a conventional approach in improving the side effects induced by cyclosporine A (CsA) and in maintaining health. The current study explored the impact of garlic on liver and testicular function, blood biochemical parameters, and oxidative stress in rats raised under cyclosporine A toxicity. It was found that the administration of garlic restored liver function and modulated lipid markers. Garlic supplementation improved the gene expression of Superoxide dismutase (SOD) and steroidogenesis genes, decreased that of collagen I-α1 (Col1a1) and transforming growth factor-1β (TGF-β1), and enhanced the antioxidant status and fertility. A combined treatment of garlic and CsA is advocated to alleviate CsA-induced oxidative stress injuries and other adverse effects.This work aimed to study the hepato-testicular protective effect of garlic in rats treated with cyclosporine A (CsA). Forty male Westar albino rats were randomly distributed in five groups (8 rats each): control, olive oil, garlic, CsA, and CsA co-treated with garlic. CsA induced an upsurge in the alanine transaminase, aspartate transaminase, and alkaline phosphatase levels and decreased albumin and total protein levels, expression of superoxide dismutase (SOD) gene, serum testosterone, triiodothyronine, and thyroxine levels compared to the control group. Additionally, there was an increase in the cholesterol, triglyceride, and low-density lipoprotein levels and a substantial reduction in the high-density lipoprotein levels compared to the control groups. Histopathological investigation of the liver showed abnormalities like hepatic cell degeneration, congestion of blood vessels, and highly active Kupffer cells in the CsA group. Histopathological examination of testes showed damaged seminiferous tubules, stoppage of the maturation of spermatogonia, and the presence of cells with irregular dense nuclei in the lumina of some tubules. For the groups treated with garlic, mitigation of the damage caused by CsA in the liver and testes, liver function tests, lipid profiles, and hormones was seen along with improved gene expression of SOD and steroidogenesis genes, and decreased gene expression of collagen I-α1 and transforming growth factor-1β. Conclusively, garlic had a positive impact on CsA-induced hepatic and sperm toxicity. It is recommended that garlic should be supplemented in transplant treatments using CsA to alleviate the cyclosporin-induced oxidative injuries and other harmful effects.

Quercetin alleviates seed germination and growth inhibition in Apocynum venetum and Apocynum pictum under mannitol-induced osmotic stress

Quercetin is one of the main flavonoids in the human diet and mainly found in different plant tissues, including seeds, flowers, leaves, stems, and roots. However, its biological function in plant tissues, especially in seeds, is unknown. In this study, the seed germination and subsequent seedling growth of Apocynum pictum and A. venetum under osmotic stress (400 mmol L−1 mannitol) supplemented with 5 μmol L−1 quercetin were evaluated after 7, 14, and 21 days of germination. Results showed that quercetin improved the germination percentage and seed vigor, as indicated by the higher germination energy, shoot length, root length, dry weight, fresh weight, and chlorophyll content in A. pictum and A. venetum seedlings under the mannitol compared with those under the mannitol alone. Quercetin decreased H2O2 and O2− production and cell membrane damage, and mostly increased the gene expression of superoxide dismutase, peroxidase, catalase, chalcone synthase and flavonol synthase in A. pictum and A. venetum seedlings under the mannitol compared with those under the mannitol alone. In addition, the germination energy of A. pictum was 21.57% higher than that of A. venetum, and the gene expression of key enzymes in quercetin biosynthesis in A. pictum was mostly higher than that in A. venetum after 1 and 7 days of germination. These results indicated that quercetin was an effective anti-osmotic agent that alleviated the adverse effect of mannitol-induced osmotic stress on seed germination and seed vigor, and A. pictum seeds were more osmotic resistant than A. venetum seeds.

The regulatory roles of yucca extract on the growth rate, hepato-renal function, histopathological alterations, and immune-related genes in common carp exposed with acute ammonia stress

The accumulation of ammonia in fish ponds regularly occurs in intensive aquaculture systems, and the inclusion of yucca extract is recognized as a practical solution to adsorb the waterborne ammonia. In this context, the study was planned to investigate the possible regulatory roles of yucca extract on the performances of common carp exposed to acute ammonia stress. Fish with similar initial weight were assigned to four groups (triplicates) where fish in the control group reared without ammonia exposure and without yucca treatment whereas the second group was exposed to ammonia (10 mg/L) without yucca treatment. The third group treated with yucca (0.75 mg/L) without ammonia while the fourth group exposed with ammonia and treated with yucca. The groups were named as the control, the ammonia, the yucca, and the ammonia/yucca. After 30 days, the growth performance, survival rate, total protein, albumin, and globulin of fish treated with yucca extract had the highest values (P < 0.05) followed by control and those exposed to acute ammonia stress and treated with yucca. The feed conversion ratio (FCR) displayed the lowest value in fish treated with yucca without ammonia stress while the highest FCR was in fish exposed to ammonia without yucca (P < 0.05). The uric acid and urea levels displayed the lowest value in fish treated with yucca without ammonia stress while the highest uric acid and urea were in fish exposed to ammonia without yucca (P < 0.05). The levels of blood creatinine, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) implemented the highest values in fish exposed to acute ammonia stress without yucca while the lowest values were in the group of fish treated with yucca without ammonia exposure (P < 0.05). The expression of hepatic catalase (CAT), superoxide dismutase (SOD), and interleukin (IL-10) genes were upregulated in fish treated with yucca and downregulated in fish exposed to acute ammonia stress. Heat shock protein (HSP70), interleukin (IL-8), tumor necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ), and interleukin (IL-1β) were upregulated in fish exposed to acute ammonia stress and downregulated in the group of fish treated with yucca extract (P < 0.05). The histopathological study revealed that fish exposed to acute ammonia stress had inflammatory and abnormal features while yucca extract induced anti-inflammation influences. Hence, the study concluded that the treatment of yucca extract is recommended to protect common carp from the toxicity of waterborne ammonia.

Moderate Hydrogen Peroxide Postconditioning Ameliorates Ischemia/Reperfusion Injury in Cardiomyocytes via STAT3-Induced Calcium, ROS, and ATP Homeostasis

Introduction: Moderate hydrogen peroxide postconditioning (H₂O₂PoC) activates signal transducer and activator of transcription 3 (STAT3) to alleviate mitochondrial calcium overload during cardiac ischemia/reperfusion (I/R). However, the initial time window of STAT3-induced calcium hemostasis, the production of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in H₂O₂PoC, and its regulated mechanism remain unknown. This study aimed to investigate H₂O₂PoC-induced homeostasis of calcium, ROS and ATP, and the role of STAT3 in the regulation. Methods: Isolated rat cardiomyocytes were exposed to H₂O₂PoC and Janus kinase 2 (JAK2)/STAT3 inhibitor AG490 during I/R. Ca²⁺ transients, cell contraction, intracellular calcium concentration, ROS production, ATP contents, phosphorylation of STAT3, gene and protein expression of manganese superoxide dismutase (MnSOD), metallothionein 1 (MT1) and metallothionein 2 (MT2), as well as activities of mitochondrial complex I and complex II were detected. Results: Moderate H₂O₂PoC improved post-ischemic Ca²⁺ transients and cell contraction recovery as well as alleviated cytosolic and mitochondrial calcium overload, which were abrogated by AG490 in rat cardiomyocytes. Moderate H₂O₂PoC increased ROS production and rate of ROS production at early reperfusion in rat I/R cardiomyocytes, and this phenomenon was also abrogated by AG490. Notably, the expression of phosphorylated nuclear STAT3; gene and protein expression of MnSOD, MT1, and MT2; and activities of mitochondrial complex I and complex II were upregulated by moderate H₂O₂PoC but downregulated by AG490. Conclusion: These findings indicated that the cardioprotection of moderate H₂O₂PoC against cardiac I/R could be associated with activated STAT3 at early reperfusion to maintain calcium, ROS, and ATP homeostasis in rat cardiomyocytes.

Therapeutic effects of Chlorella vulgaris on carbon tetrachloride induced liver fibrosis by targeting Hippo signaling pathway and AMPK/FOXO1 axis.

This study was conducted to present the mechanism of the therapeutic effects of Chlorella vulgaris extract (CV) on the carbon tetrachloride (CCl4) induced liver fibrosis model. Primarily, the mechanism of antioxidant effects of CV were investigated via measuring the expression of forkhead box protein O1 (FOXO1) and phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK) as upstream regulators of superoxide dismutase (SOD) and catalase (CAT). Subsequently, we investigated the regulatory effect of CV treatment on the yes-associated protein (YAP) and transcriptional coactivators with a PDZ-binding motif (TAZ) as fibrogenic factors. Male Wistar rats received CCl4 and olive oil solution 1ml/kg intraperitoneally for 12weeks, twice weekly. CV 50 and 100mg/kg were administered on a daily basis by gavage in the last 4weeks. Ultimately, liver marker enzymes and hepatic hydroxyproline content were measured. The activity of SOD and CAT and the expression of YAP, TAZ, FOXO1, SOD, and CAT were analyzed. Finally, the protein levels of YAP, TAZ, and p-AMPK were detected. CV administration decreased liver marker enzymes and hydroxyproline content significantly. The expression and protein levels of YAP and TAZ reduced by CV treatment. Furthermore, the augmentation of expression and function of CAT and SOD by CV treatment was followed by an increase in the expression of FOXO1 and protein level of p-AMPK. Our data revealed that the stimulation of expression and function of SOD and CAT by CV treatment could be mediated by FOXO1/p-AMPK axis. Moreover, anti-fibrotic effect of CV might be associated with its inhibitory effect on the hepatic expression of YAP and TAZ. Chlorella vulgaris treatment ameliorates liver fibrosis via two cellular mechanisms. A) Likely, Chlorella vulgaris treatment increases gene expression of enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) via upregulating its upstream regulatory elements i.e. phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK) and forkhead box protein O1 (FOXO1). These possible regulatory effects maybe lead to reduce reactive oxygen species level (ROS). B) Chlorella vulgaris treatment decreases hepatic protein level and gene expression of key elements of Hippo signaling pathway i.e. Yes-associated protein (YAP) and Transcriptional coactivators with a PDZ-binding motif (TAZ). Figure created with BioRender ( https://biorender.com ). ROS: Reactive oxygen species, YAP: Yes-associated protein, TAZ: Transcriptional coactivators with a PDZ-binding motif, FOXO1: Fork head Box O1, AMPK: 5' adenosine monophosphate activated protein kinase, SOD: Superoxide dismutase, CAT: Catalase, P: Phosphate group.

Purple Sweet Potato Extract extends lifespan by activating autophagy pathway in male Drosophila melanogaster.

Purple sweet potato is a nutritive food rich in anthocyanins that possess antioxidant effects. Drosophila melanogaster owns short growth cycle, fast reproduction, less chromosomes, more mutants, small individuals, therefore, which is an appropriate genetic model organism. To investigate the anti-aging activity of Purple Sweet Potato Extract (PSPE) in male Drosophila melanogaster and explore the underlying mechanism. PSPE-induced longevity was associated with improvements in climbing ability and tolerance to stressors such as paraquat and hydrogen peroxide (H2O2). Furthermore, PSPE supplementation increased the activity of superoxide dismutase (SOD) and catalase (CAT), as well as expression of SOD and CAT genes, but decreased malondialdehyde (MDA) content. Meanwhile, PSPE decreased the intestinal stem cells (ISCs) proliferation and improved intestinal homeostasis, which was measured by Smurf assay and colony-forming units (CFUs) measurement in aging flies. Additionally, PSPE markedly inhibited the expression of upstream genes AKT-1, PI3K and mTOR and elevated the downstream gene 4E-BP, which further activated the expression of autophagy-related genes (Atg1, Atg5, Atg8a and Atg8b). Moreover, the production of lysosomes increased, indicating that the autophagy pathway was activated. The results provided direct evidence of PSPE anti-aging effects on an organism level, indicating PSPE could be developed for use in effective anti-aging products.

Dietary arsenic supplementation induces oxidative stress by suppressing nuclear factor erythroid 2-related factor 2 in the livers and kidneys of laying hens

This study investigated the effects of dietary arsenic supplementation on laying performance, egg quality, hepatic and renal histopathology, and oxidative stress in the livers and kidneys of laying hens. Furthermore, the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway was explored to reveal the molecular mechanism of the stress. Five hundred and twelve 40-week-old Hyline White laying hens were randomly allocated to 4 groups with 8 pens per group and 16 hens per pen. The doses of arsenic administered to the 4 groups were 0.95, 20.78, 40.67, and 60.25 mg/kg. The results revealed that dietary arsenic supplementation significantly reduced hen-day egg production (P < 0.05), average egg weight (P < 0.05), Haugh units (P < 0.05), albumen height (P < 0.05), and eggshell strength (P < 0.05). Dietary arsenic supplementation also induced the accumulation of arsenic and histopathological damages in the liver and kidney. In accordance, dietary arsenic supplementation significantly enhanced serum alanine aminotransferase (P < 0.05), aspartate aminotransferase (P < 0.05), blood urea nitrogen (P < 0.05), and uric acid (P < 0.05) levels. After arsenic exposure, the activities of superoxide dismutase (SOD) (P < 0.05), catalase (P < 0.01), glutathione reductase (P < 0.05), and glutathione peroxidase (P < 0.05), and glutathione content (P < 0.05) were significantly decreased, while the malondialdehyde level was significantly increased (P < 0.05) in the liver and kidney. Positive correlations occurred between antioxidant enzyme activities and antioxidant enzyme gene expressions in the liver and kidney, except for renal manganese superoxide dismutase gene expression and SOD activity. Additionally, hepatic and renal Nrf2 mRNA expression was positively correlated with antioxidant gene expressions and negatively correlated with Keap1 mRNA expression. In summary, dietary arsenic supplementation induced oxidative stress by suppressing the Nrf2-Keap1 pathway in the livers and kidneys of laying hens.

Functional and molecular evaluation of using aliskiren during acute and chronic partial ureteral obstruction in rat solitary kidney

AimsTo study the effect of direct renin inhibitor (aliskiren) on the renal function during acute and chronic partial ureteral obstruction (PUO) in rat solitary kidney. Main methodsSixty male Sprague–Dawley rats were randomly allocated into three groups (20 rats each); sham, PUO and aliskiren groups. Right nephrectomy was performed in all groups. Rats in PUO and aliskiren groups were subjected to left PUO and received no treatment and aliskiren (10 mg/kg, orally, once per day till sacrification), respectively. Blood samples were then collected for biochemical measurements. Ten rats from each group were sacrificed after two weeks, while the remaining rats were sacrificed after four weeks. Left kidneys were harvested for histopathological examination, BCL-2, interleukin (IL)-6, transforming growth factor (TGF)-β1, collagen I and fibronectin relative gene expression and assessment of glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) activity. Key findingsAfter two and four weeks of PUO, aliskiren significantly recompensed the rise of serum creatinine (Scr) and blood urea nitrogen (BUN). Aliskiren also revealed significantly better histopathological results regarding cortical and medullary necrosis, regeneration and inflammatory cell infiltration. Aliskiren group showed statistically significant up-regulation of BCL-2 and down-regulation of IL-6, TGF-β1, collagen I and fibronectin relative gene expression. Aliskiren significantly increased GSH and SOD activity and reduced MDA and NO activity. Moreover, aliskiren administration for four weeks after PUO significantly yielded more renoprotective effect compared to its administration for two weeks. SignificanceAliskiren ameliorates the deterioration of the renal function during acute and chronic PUO in a solitary kidney.