GPX1 Gene Expression Research Articles

5-Aminolevulinic acid treatment mitigates pesticide stress in bean seedlings by regulating stress-related gene expression and retrotransposon movements

Overdoses of pesticides lead to a decrease in the yield and quality of plants, such as beans. The unconscious use of deltamethrin, one of the synthetic insecticides, increases the amount of reactive oxygen species (ROS) by causing oxidative stress in plants. In this case, plants tolerate stress by activating the antioxidant defense mechanism and many genes. 5-Aminolevulinic acid (ALA) improves tolerance to stress by acting exogenously in low doses. There are many gene families that are effective in the regulation of this mechanism. In addition, one of the response mechanisms at the molecular level against environmental stressors in plants is retrotransposon movement. In this study, the expression levels of superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR), and stress-associated protein (SAP) genes were determined by Q-PCR in deltamethrin (0.5 ppm) and various doses (20, 40, and 80 mg/l) of ALA-treated bean seedlings. In addition, one of the response mechanisms at the molecular level against environmental stressors in plants is retrotransposon movement. It was determined that deltamethrin increased the expression of SOD (1.8-fold), GPX (1.4-fold), CAT (2.7-fold), and SAP (2.5-fold) genes, while 20 and 40 mg/l ALA gradually increased the expression of these genes at levels close to control, but 80 mg/l ALA increased the expression of these genes almost to the same level as deltamethrin (2.1-fold, 1.4-fold, 2.6-fold, and 2.6-fold in SOD, GPX, CAT, and SAP genes, respectively). In addition, retrotransposon-microsatellite amplified polymorphism (REMAP) was performed to determine the polymorphism caused by retrotransposon movements. While deltamethrin treatment has caused a decrease in genomic template stability (GTS) (27%), ALA treatments have prevented this decline. At doses of 20, 40, and 80 mg/L of ALA treatments, the GTS ratios were determined to be 96.8%, 74.6%, and 58.7%, respectively. Collectively, these findings demonstrated that ALA has the utility of alleviating pesticide stress effects on beans.

Silybum marianum promotes growth, hepatic antioxidative activity, and splenic immunity but does not influence the intestinal barrier function of Nile tilapia, Oreochromis niloticus

Alternative additives such as phytobiotics have been a research priority to promote chemotherapeutic-free and disease-resistant aquaculture. Hence, various Silybum marianum (SM) extract levels, including 1, 2, 3, and 4 g kg−1, were supplemented with a reference diet, and the reference diet containing no SM was considered a control. Each test diet was fed in triplicate to experimental fish for 60 days. The effects were observed on growth, liver, lymphoid organs (kidney and spleen), and intestinal health in relation to a panel of blood biochemical responses of Nile tilapia, Oreochromis niloticus. Better growth performance in Nile tilapia fed any supplementation levels of SM resulted from improved feed utilization and feed conversion ratio. Microscopic observations found normal kidney, liver, and spleen microstructure across all treatments. Of interest, the antioxidative capacity of the liver was stimulated by SM supplementation, supported by higher expression of CAT, SOD, and GPx genes coupled with higher levels of hepatic GST and T-AOC and lower levels of hepatic MDA concentrations. This was further aligned with lower levels of serum ALP, AST, and ALT relevant to liver function. Meanwhile, splenic immune relevant gene expression (IFN-γ1, LYZ, and hepcidin) increased significantly in all SM-treated fish compared to the control group. Also, hematological responses, including red blood cell indices (RBCs, Hb, HTC, PCV, MCV, MCH, and MCHC) and white blood cell indices (WBCs, lymphocytes, eosinophils, basophils, and heterophils), except monocytes, were improved by SM supplementation. Intestinal microstructures were normal, and their barrier functions were unchanged by dietary supplementation. Hence, SM extract could be used as a promising avenue for enhancing the functionality of aquadiet, leading to improving overall health performance. However, the mode of action of the bioactive ingredients present in SM extract is warranted to be further studied to consider SM as a functional additive for aquafeeds.

Chicken egg lysozyme enhanced the growth performance, feed utilization, upregulated immune-related genes, and mitigated the impacts of Aeromonas hydrophila infection in Nile tilapia (Oreochromisniloticus)

Functional supplements, including lysozyme, are highly approved as immunostimulant and antibacterial agents with a high potential for use in aquaculture. In this regard, Nile tilapia was treated with lysozyme at 0, 0.5, 1, 1.5, and 3 g/kg for 60 days, then challenged with Aeromonas hydrophila. Fish were stocked in 15 glass aquaria (70 L each) with an equal initial weight of 10.72 ± 0.71 g per fish and 15 fish per aquarium. The regression analysis revealed that dietary lysozyme supplementation at 1.83–2 g/kg enhanced the growth performance, protein efficiency ratio, and protein productive value while reducing the feed conversion ratio of tilapia. Markedly, tilapia treated with lysozyme had a low mortality rate (30–50 %) compared to the control, which recorded a 70 % mortality rate after 15 days of challenge with A. hydrophila. The regression analysis also revealed that the highest lysozyme activity of tilapia-fed lysozyme for 60 days is achieved by 2.05 g/kg lysozyme. The expression of Nf-κb, IL-1β, and IL-8 genes is upregulated in tilapia-fed lysozyme at 0.5, 1, 1.5, and 3 g/kg for 60 days before and after A. hydrophila infection. The expression of GPX and CAT genes was higher in tilapia-fed lysozyme at 0.5, 1, 1.5, and 3 g/kg for 60 days before and after A. hydrophila infection. Before infection, the relative transcription of the lysozyme and C3 was upregulated in tilapia-fed lysozyme at 0.5, 1, 1.5, and 3 g/kg. However, lysozyme gene expression in tilapia treated with 0.5 g/kg lysozyme had no significant differences from those fed 0 g/kg lysozyme. After infection, the relative transcription of the lysozyme gene was upregulated in tilapia fed 1 and 1.5 g/kg, while tilapia fed 1 g/kg lysozyme had the highest C3 gene transcription. After infection, the hepatocytes in the livers of fish fed 0 g/kg lysozyme exhibited a noticeable fatty alteration, along with congestion, a light infiltration of inflammatory cells, and the start of necrosed cell regeneration. However, the livers of fish that received lysozyme were normal except for infiltrations of perivascular and interstitial mononuclear cells, depending on the supplementation dose. In conclusion, dietary lysozyme is recommended at 1.83–2.05 g/kg to gain high growth performance, immune response, and high resistance to A. hydrophila in Nile tilapia.

Effect of Adding Taurine on Gene Expression of GPX1 and ACACA Genes of Broiler Chickens Raised at Different Temperatures

This study was conducted in animal production farm in Collage Agriculture - University of Anbar during 7/8 – 17/9/2022 during summer and 25/2–7/4/2023 in winter to study the effect of addition different levels of taurine to diet in gene expression of GPX1 and ACACA genes of broiler chickens (Ross 308) raised at different temperatures during the summer and winter seasons. 180 one day unsexed hatched chicks will distributed into five treatments with three replicates for each treatment, as the following T1, control treatment, T2 adding 300 mg of vitamin C per kg diet during summer and 300 mg of vitamin D in winter, T3, T4 and T5 adding 300,600 and 900 mg of taurine per kg diet respectively. The results of the statistical analysis of the two experiments showed significant effect (P≤0.01) of the addition treatments on gene expression values of the ACACA gene, as the treatments T3-T5 recorded the lowest values of gene expression during the summer and winter seasons compared to the t1 treatment. As for the gene expression of the GPX1 enzyme, the treatment T5 and T2 recorded the lowest values of gene expression during the summer and winter seasons, respectively.

Single-Cell Sequencing Reveals a Close Correlation between the Number of MDSCs and the Gene Expression Levels of GPX1 and S100A8/S100A9 in Patients with Myelofibrosis

Myelofibrosis is a type of myeloproliferative disorder, and research indicates that the immunosuppressive tumor microenvironment plays a significant role in the pathogenesis of myelofibrosis, with myeloid-derived suppressor cells (MDSCs) being the primary inhibitory cells involved in shaping the tumor immune microenvironment. In this study, we used flow cytometry to detect the number of MDSCs in the bone marrow of myelofibrosis patients and revealed the relationship between MDSCs and gene expression levels through single-cell transcriptome sequencing. We utilized flow cytometry to identify the number of Lin-HLA-DR-CD33+ labeled MDSCs in the bone marrow of 56 myelofibrosis patients and 20 healthy individuals. Additionally, we performed single-cell transcriptome sequencing on samples from two myelofibrosis patients, one showing a favorable response to Lurcitanib treatment and the other showing an ineffective response. The results of flow cytometry revealed a significant increase in the percentage of MDSCs in the bone marrow of myelofibrosis patients (15.16±6.25%) compared to healthy individuals (1.72±0.88%) (p<0.0001) (Fig a, b). Among the two patients subjected to single-cell sequencing, the percentage of MDSCs in their samples was 19.3% and 8.9% (Fig c). Following treatment with different concentrations of decitabine, the MDSCs cell count progressively decreased with increasing treatment time and concentration (Fig d).Subsequently, we identified the major cell types in the two samples through single-cell sequencing, which included T cells, Neutrophils, Monocytes, Erythroblasts, B cells, Platelets, Myelocytes, Hematopoietic Stem Cells（HSCs）, and progenitor Myelocytes (Fig e). The analysis of marker gene expression for each major cell type showed good specificity (Fig f). By comparing the proportions of different cell types between the two samples, it was observed that the high MDSC group had a decrease in the proportions of B cells, T cells, Monocytes, and Platelets, while an increase in the proportions of Neutrophils, Erythroblasts, HSC, Myelocytes, and progenitor Myelocytes (Fig g).Furthermore, we analyzed the highly differentially expressed genes in different cell types and identified significantly enriched pathways. The results showed significant downregulation of the GPX1 gene in monocytes of the high MDSC group, whereas the S100A8/S100A9 genes were significantly upregulated in HSC (Fig h). Enrichment analysis revealed significant enrichment of pathways related to reactive oxygen species metabolism, immune-inflammatory response, etc., in monocytes of the high MDSCs group, and significant enrichment of pathways related to NF-kappaB transcription factor activity regulation, Jak-STATs signaling, mTOR signaling in HSC. Research has shown that the number of MDSCs is elevated in patients with myelofibrosis . Lurcitanib exhibits poor therapeutic efficacy in myelofibrosis patients with high MDSCs counts, whereas decitabine demonstrates more favorable treatment outcomes. Single-cell sequencing results revealed significant downregulation of the GPX1 gene in monocytes of myelofibrosis patients with high MDSCs counts. GPX1 gene encodes glutathione peroxidase 1, which plays a role in reducing oxidative stress and inflammation, and has anti-fibrotic effects.Conversely, in HSC of myelofibrosis patients with high MDSCs counts, the S100A8/S100A9 gene expression is significantly upregulated. This gene can induce neutrophil chemotaxis and adhesion, serving as a danger-associated molecular pattern (DAMP) molecule and stimulating innate immune cells through pattern recognition receptors (e.g., TLR4 and AGER), subsequently activating MAP kinase and NF-kappa-B signaling pathways, leading to inflammation and fibrosis.Thus, it can be inferred that the number of MDSCs in myelofibrosis patients is negatively correlated with GPX1 gene expression and positively correlated with S100A8/S100A9 gene expression. Acknowledgement: This research was funded by the Key R&D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; Zhejiang Medical Association Clinical Medical Research special fund project, No. 2022ZYC-D09. Correspondence to: Dr Jian Huang, Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine. househuang@zju.edu.cn

Effects of hydroxy methionine zinc on growth performance, immune response, antioxidant capacity, and intestinal microbiota of red claw crayfish (Procambarus clarkii)

This study aimed to evaluate the effects of varying zinc (Zn) levels on the growth performance, non-specific immune response, antioxidant capacity, and intestinal microbiota of red claw crayfish (Procambarus clarkii (P. clarkii)). Adopting hydroxy methionine zinc (Zn-MHA) as the Zn source, 180 healthy crayfish with an initial body mass of 6.50 ± 0.05 g were randomly divided into the following five groups: X1 (control group) and groups X2, X3, X4, and X5, which were fed the basal feed supplemented with Zn-MHA with 0, 15, 30, 60, and 90 mg kg−1, respectively. The results indicated that following the addition of various concentrations of Zn-MHA to the diet, the following was observed: Specific growth rate (SGR), weight gain rate (WGR), total protein (TP), total cholesterol (TC), the activities of alkaline phosphatase (AKP), phenoloxidase (PO), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) and catalase (CAT), the expression of CTL, GPX, and CuZn-SOD genes demonstrated a trend of rising and then declining—with a maximum value in group X4—which was significantly higher than that in group X1 (P < 0.05). Zn deposition in the intestine and hepatopancreas, the activity of GSH-PX, and the expression of GSH-PX were increased, exhibiting the highest value in group X5. The malonaldehyde (MDA) content was significantly reduced, with the lowest value in group X4, and the MDA content of the Zn-MHA addition groups were significantly lower than the control group (P < 0.05). In the analysis of the intestinal microbiota of P. clarkii, the number of operational taxonomic units in group X4 was the highest, and the richness and diversity indexes of groups X3 and X4 were significantly higher than those in group X1 (P < 0.05). Meanwhile, the dietary addition of Zn-MHA decreased and increased the relative abundance of Proteobacteria and Tenericutes, respectively. These findings indicate that supplementation of dietary Zn-MHA at an optimum dose of 60 mg kg−1 may effectively improve growth performance, immune response, antioxidant capacity, and intestinal microbiota richness and species diversity in crayfish.

Antioxidant activity of Carica papaya &Persea americana fruits against cadmium induced neurotoxicity, nephrotoxicity, and hepatotoxicity in rats with a computational approach

BackgroundCadmium is widely reported to interfere with the proper functioning of cells by disrupting cellular redox balance, causing apoptosis, and leading to hepatocellular damage, neurotoxicity, pulmonary edema, cancer, and cardiac and neurodegenerative diseases. Treatment of Cd toxicity with drugs brings undesirable side effects, making it necessary to remove Cd from the body safely without harmful effects. ObjectiveThis study aimed to determine how Cd causing malfunctioning of cells could be treated with antioxidant-rich avocado and papaya fruit juices. This work fixated on elucidating and comparing the effects of avocado and papaya fruit juice on Cd-dependent impairment in memory and spatial learning. In addition, various markers of tissue damage, such as the concentration of biomarkers in liver and kidney tissue, the expression of antioxidant enzymes and Cd-induced lipid peroxidation, were analyzed. Methodologyin silico studies of the phytochemical constituents of avocado and papaya (ligands) were docked against antioxidant enzymes Catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) as macromolecules showed strong hydrogen binding with significant binding capacities. To develop the Cd in vivo model, rats were administered CdCl2 (200 ppm) in drinking water for 7 weeks. After induction of Cd toxicity, rats were post-treated with avocado and papaya (10% w/v each) in a standard diet. After post-treatment, memory and learning were assessed using the Morris water maze behavioural test. Biochemical tests for liver and kidney biomarkers were monitored. To determine the level of ROS, lipid peroxidation was determined by Malondialdehyde (MDA) assay. Gene expression of SOD, CAT and GPx were determined via qRT-PCR. ResultsThis study demonstrated that Cd accumulation in the liver, kidney and hippocampal tissues was reduced after treatment with avocado and papaya. SOD, CAT and GPX gene expression were upregulated after avocado and papaya juice treatment. Moreover, a comparative analysis between avocado and papaya fruit juices clarified that papaya has more active potential for improving memory and learning, upregulating the expression of antioxidant enzymes, and reducing lipid peroxidation in the liver, kidney, and hippocampus. ConclusionThis study suggests that a diet containing papaya and avocado can help treat the lethal effects caused by Cd. Because their active constituents can improve health at the cellular and molecular levels.

PSVI-14 Mitigating the Negative Effects of Heat Stress in Grow-Finish Pigs Using Water Delivered Oregano Essential Oil

Abstract Grow-finish pigs (n = 192) were used in a 28-day experiment to determine if adding oregano essential oil to the water would mitigate the detrimental effects of heat stress. Pigs (initial BW = 51.9 kg) were blocked by sex and BW and randomly allotted to a 2x2 factorial arrangement of water treatment (oregano essential oil vs. control) and environment (heat stress vs. thermoneutral). There were 6 pigs/pen (4 barrows and 2 gilts/pen) and 8 pens/treatment. Pigs were given 15 d to acclimate to pens and water treatment under thermoneutral conditions (21.1℃). Following acclimation, one-half the pigs were subjected to a 3-day diurnal heat stress (12 h at 33.3℃ and 12 h at 26.7℃). On d 22 of the experiment (3 d post-heat stress), one barrow/pen was euthanized; jejunal mucosa scrapings were collected, flash frozen in liquid nitrogen, and stored at -80oC for subsequent RNA isolation and cDNA creation. Gene expression of CDKN1A, TP53, GPX1, SOD1, SLC2A2, SLC2A5, and MUC2 were determined by qPCR using SYBR green, normalized using housekeeper genes and expressed relative to the control treatment using the 2-ΔΔCT method. Data were analyzed as RCB using GLM procedure in SAS 9.4 with fixed effects of water treatment, environment, and the interaction. Heat-stressed pigs had reduced ADG (P &amp;lt; 0.003) and Gain:Feed (P &amp;lt; 0.008) during the 3d heat stress compared with pigs housed in thermoneutral conditions. Post-heat stress, ADG (P &amp;lt; 0.001) and Gain:Feed (P &amp;lt; 0.001) increased in previously heat-stressed pigs compared with thermoneutral pigs. There was no effect of oregano supplementation before or during heat stress. However, in the post-heat stress period, ADG was increased (P &amp;lt; 0.05) by oregano supplementation in the water for both heat stressed and non-heat stressed pigs. Oregano supplementation did not affect ADFI before heat stress. An interaction (P &amp;lt; 0.005) of heat stress and water treatment was observed for ADFI during heat stress and after heat stress. During heat stress, oregano supplementation resulted in reduced feed intake. Post-heat stress ADFI was lowest for non-heat stressed pigs with no oregano supplementation. Oregano essential oil increased water consumption before (P &amp;lt; 0.02), during (P &amp;lt; 0.03), and after heat stress (P &amp;lt; 0.02), with an overall increase in water consumption of 35% compared with control pigs (P &amp;lt; 0.04). No interactions of heat stress and oregano supplementation were observed for gene expression. SLC2A2 expression tended (P &amp;lt; 0.08) to be downregulated when oregano essential oils were added to the water and upregulated following an acute heat stress. SLC2A5 expression was increased in pigs given oregano compared with control pigs (P &amp;lt; 0.02), but was unaffected by heat stress. Water delivered oregano essential oil increased water intake and had a slight effect on intestinal gene expression but did not mitigate the effects of a short-term heat stress.

Dietary arginine levels affect growth performance, intestinal antioxidant capacity and immune responses in largemouth bass (Micropterus salmoides)

This study explored the role of dietary arginine level (DAL) on growth, intestinal antioxidant status and immune response in juvenile largemouth bass (Micropterus salmoides), providing guidance for the optimization of commercial feed in largemouth bass. Six graded arginine levels in diets were fed to the fish for 8 weeks (1.96%, 2.28%, 2.52%, 2.81%, 3.09% and 3.35% diets). The findings were as follows: with increasing DALs, FW, WG and SGR increased first and decreased, and FCR showed the opposite trend. There was no difference in the contents of crude protein and ash among graded DAL (P > 0.05). DAL (3.09% and 3.35%) significantly increased the activities of plasma AST (P < 0.05). Certain range of dietary arginine levels could improve antioxidant ability by regulating intestinal antioxidant-related parameters including the activities of SOD, GPx, and the contents of GSH and MDA. The gene expression of Nrf2 was significantly increased in response to 2.52% DAL, while Keap1 expression was decreased (P < 0.05). Furthermore, 1.96% and 2.28% DALs significantly increased the gene expression of CAT and GPx (P < 0.05), and SOD expression was the highest in response to 2.52% and 2.81% DALs (P < 0.05). Compared with the control group, the relative expressions of IL-1β, IL-8, TNF-α and NF-κB were reduced that were fed 2.52%− 3.35% DALs. Moreover, the relative expression of IL-10 and TGF-β were peaked in response to 2.81% DAL (P < 0.05). The quadratic regression curve analysis according to the growth results of SGR and FCR, the expressions of IL-10 and TGF-β showed that the optimal dietary arginine requirement for largemouth bass were 2.40%− 2.63% (5.03%−5.46% of dietary protein), and could promote growth, intestinal antioxidant capacity and immune responses in juvenile largemouth bass.

Deletion of IL-1β exacerbates acrylamide-induced neurotoxicity in mice.

Acrylamide is a neurotoxicant in human and experimental animals. Interleukin-1β (IL-1β) is a proinflammatory cytokine known as a critical component of brain reaction to any insult or neurodegenerative pathologies, though its role in electrophile-induced neurotoxicity remains elusive. The aim of this study was to investigate the role of IL-1β in acrylamide-induced neurotoxicity in mice. Ten-week-old male wild-type and IL-1β knock-out mice were allocated into 3 groups each and exposed to acrylamide at 0, 12.5, 25 mg/kg body weight by oral gavage for 28 days. Compared with wild-type mice, the results showed a significant increase in landing foot spread test and a significant decrease in density of cortical noradrenergic axons in IL-1β KO mice exposed to acrylamide at 25 mg/kg body weight. Exposure to acrylamide at 25 mg/kg significantly increased cortical gene expression of Gclc, Gpx1, and Gpx4 in wild-type mice but decreased them in IL-1β KO mice. The same exposure level significantly increased total glutathione and oxidized glutathione (GSSG) in the cerebellum of wild-type mice but neither changed total glutathione nor decreased GSSG in the cerebellum of IL-1β KO mice. The basal level of malondialdehyde in the cerebellum was higher in IL-1β KO mice than in wild-type mice. The results suggest that IL-1β protects the mouse brain against acrylamide-induced neurotoxicity, probably through suppression of oxidative stress by glutathione synthesis and peroxidation. This unexpected result provides new insight on the protective role of IL-1β in acrylamide-induced neurotoxicity.

Dose-dependent stress response of esfenvalerate insecticide on common carp (Cyprinus carpio): Evaluating blood parameters and gene expression

Esfenvalerate is a pyrethroid insecticide used primarily in the agriculture sector for insect management. Esfenvalerate is effective against a wide range of harmful insects, including flies, cockroaches, locusts, and many other types of bugs. It is also known that esfenvalerate has toxic effects on aquatic organisms and poses significant environmental concerns. In this study, the aim is to subchronically examine the effects of sublethal concentrations of esfenvalerate insecticide on common carp (Cyprinus carpio) by assessing changes in blood parameters and resulting gene expression. For this purpose, common carp (Cyprinus carpio) were divided into 5 groups and exposed to 0.025, 0.05, 0.1, and 0.15 μg/L concentrations of esfenvalerate for a period of 14 days. Blood and liver tissue samples were collected from the fish that underwent weight and length measurements. The effects on gene expression levels of immune, antioxidant, and stress-related genes in the liver tissue, including SOD, GST, Cortisol receptor, HSP70, H+−ATPase, Na+/K+−ATPase, Catalase, and GpX, were evaluated, as were the hematological and serum biochemical parameters. Significant decreases were observed in the levels of hematocrit, hemoglobin, erythrocytes, triglycerides and total protein and catalase, H+−ATPase, and GpX gene expression. Glucose, cholesterol, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH) and alkaline phosphatase (ALP), SOD, Cortisol receptor, Na+/K+−ATPase gene expression levels increased. As a result, it has been revealed that esfenvalerate insecticide causes oxidative stress in carp at all dose ranges.

Effect of Quinolinic Acid on Behavior, Morphology, and Expression of Inflammatory/oxidative Status in Rats' Striatum: Is Coenzyme Q10 a Good Protector?

Quinolinic acid (QUIN) is a toxic compound with pro-oxidant, pro-inflammatory, and pro-apoptotic actions found at high levels in the central nervous system (CNS) in several pathological conditions. Due to the toxicity of QUIN, it is important to evaluate strategies to protect against the damage caused by this metabolite in the brain. In this context, coenzyme Q10 (CoQ10) is a provitamin present in the mitochondria with a protective role in cells through several mechanisms of action. Based on these, the present study was aimed at evaluating the possible neuroprotective role of CoQ10 against damage caused by QUIN in the striatum of young Wistar rats. Twenty-one-day-old rats underwent a 10-day pretreatment with CoQ10 or saline (control) intraperitoneal injections and on the 30th day of life received QUIN intrastriatal or saline (control) administration. The animals were submitted to behavior tests or euthanized, and the striatum was dissected to neurochemical studies. Results showed that CoQ10 was able to prevent behavioral changes (the open field, object recognition, and pole test tasks) and neurochemical parameters (alteration in the gene expression of IL-1β, IL-6, SOD, and GPx, as well as in the immunocontent of cytoplasmic Nrf2 and nuclear p-Nf-κβ) caused by QUIN. These findings demonstrate the promising therapeutic effects of CoQ10 against QUIN toxicity.

Enhancing Healthcare Outcomes and Modulating Apoptosis- and Antioxidant-Related Genes through the Nano-Phytosomal Delivery of Phenolics Extracted from Allium ampeloprasum.

The application of nano drug delivery systems, particularly those utilizing natural bioactive compounds with anticancer properties, has gained significant attention. In this study, a novel nano-phytosome-loaded phenolic rich fraction (PRF) derived from Allium ampeloprasum L. was developed. The antitumor activity of the formulation was evaluated in BALB/c mice with TUBO colon carcinoma. The PRF-loaded nano-phytosome (PRF-NPs) exhibited a sphere-shaped structure (226 nm) and contained a diverse range of phenolic compounds. Animal trials conducted on TUBO tumor-bearing mice demonstrated that treatment with PRF-NPs at a dosage of 50 mg TPC/Kg/BW resulted in significant improvements in body weight and food intake, while reducing liver enzymes and lipid peroxidation. The expression of apoptosis-related genes, such as Bax and caspase-3, was upregulated, whereas Bcl2 was significantly downregulated (p < 0.05). Furthermore, the expression of GPx and SOD genes in the liver was notably increased compared to the control group. The findings suggest that the phytosomal encapsulation of the phenolic rich fraction derived from Allium ampeloprasum L. can enhance the bioavailability of natural phytochemicals and improve their antitumor properties. The development of PRF-NPs as a nano drug delivery system holds promise for effective breast cancer treatment.

Vitamin D Supplementation Combined With Aerobic Training Increases the Gene Expression of Antioxidants in Kidney Tissue in Healthy Middle-Aged Rats

Background &amp; : Both exercise and vitamin D can affect oxidative stress indicators. Despite this, their interaction at the level of kidney tissue has been less investigated. Hence, the main objective of the present study was to determine the effect of vitamin D supplementation and aerobic training on oxidative stress markers in the kidney tissue of middle-aged male rats. Materials and Methods: 20 Wistar male rats (14–12 months and 350–400 g ) were randomly divided into 4 groups: control (CON), aerobic training (EXE), vitamin D (VD) and aerobic training + vitamin D (EXE+VD). Exercise consisted of eight weeks of aerobic training (5 day/week). The VD and EXE+VD groups received vitamin D (500 units/kg) on a daily basis. Olive oil was also used as a placebo. 48 hours after the last intervention session, animal tissues were removed. The gene expression Oxidative stress biomarkers (CAT, Mn-SOD, GPx and XO) were measured by real-time PCR. Data analysis was performed by one-way ANOVA test at the level of P &lt;0.05. Results: The results showed that the EXE+VD increased the gene expression of Mn-SOD, CAT and GPx (P &lt;0.05) and decreased the expression of XO (P &lt;0.05). Also, VD had no effect on the expression of antioxidant enzymes and XO (P&gt;0.05). EXE increased CAT and Mn-SOD expression compared to the CON (P&lt;0.05) and decreased XO expression. Also, CAT values in EXE were significantly higher than VD (P&lt;0.05). Conclusion: According to the results of the present study, it seems that the VD+EXE can increase antioxidant defense and reduce the oxidative stress of kidney tissue.

Anti-oxidant effect of nitrite in the pancreatic islets of type 2 diabetic male rats.

Nitrite, a nitric oxide (NO) donor, increases insulin secretion from pancreatic islets and has positive metabolic effects in type 2 diabetes (T2D). Here, we test the hypothesis of whether nitrite-induced insulin secretion is due to blunting of diabetes-induced oxidative stress in the islets. T2D was created in male rats using a combination of streptozotocin at 25 mg/kg and a high-fat diet. Wistar rats were assigned to 3 groups (n=6 in each group), including control, T2D, and T2D+nitrite; the latter group consumed drinking water containing sodium nitrite (50 mg/l) for eight weeks. At the end of the study, mRNA levels of NADPH oxidase (Nox1, 2, 3, and 4), superoxide dismutase (SOD1, 2, and 3), glutathione peroxides (GPX1 and 7), glutathione reductase (GR), catalase, thioredoxin (TXN1 and 2), and thioredoxin reductase (TXNRD1) were measured in the isolated pancreatic islets. In the islets of diabetic rats, mRNA expressions of Nox1, 2, and 4 were higher, whereas expressions of SOD1, 2, catalase, GPX1, 7, GR, and TXN1 were lower than controls. Nitrite significantly (all P-values<0.05) decreased gene expression of Nox1 (0.39-fold) and Nox4 (0.23-fold) and increased gene expression of SOD1 (2.2-fold), SOD2 (2.8-fold), catalase (2.7-fold), GPX1 (2.2-fold), GPX7 (6.0-fold), GR (3.0-fold), TXN1 (2.1-fold), and TXNRD1 (2.3-fold) in diabetic rats. Nitrite decreased oxidative stress in isolated pancreatic islets of rats with T2D by suppressing oxidants and augmenting anti-oxidants. These findings favor the notion that nitrite-induced insulin secretion is partially due to decreased oxidative stress.

Microcapsules loaded with date seed extract and its inhibitory potential to modulate the toxic effects of mycotoxins in mice received mold-contaminated diet

Mycotoxins are the secondary fungal metabolites generally produced by wide range of fungi including aflatoxins (AF), ochratoxin A (OTA), fumonisins (FB), zearalenone (ZEN), and deoxynivalenol (DON). Nowadays, they are main concern to food and agricultural commodities due to undesirable health and socio-economic effect. This investigation was designed to synthesized microcapsules loaded the bioactive compounds of date seed and evaluated its inhibitory activities in mice received mold-contaminated diet. The finding revealed that the developed microcapsule is homogenous and mostly spherical with size of 2.58 μm with acceptable PDI of 0.21. The main phytochemical has been confirmed by HPLC analysis were xylose, fructose, mannose, glucose, and galactose with the respective values of 41.95%, 2.24%, 5.27%, and 0.169%. The in vivo analyses manifested that the mice received date seed microcapsules significantly (p < 0.05) improved the average daily weight gain, feed intake, liver enzymes (ALT, ALP, and AST), and lipid peroxidation values compare to mice group received mycotoxin-contaminated diet. Furthermore, encapsulation date seed bioactive compounds notably up-regulated the expression of GPx, SOD, IFN-γ, and IL-2 genes while down-regulated the iNOS gene. Consequently, the novel microcapsules loaded date seed is suggested to be considered as a promising mycotoxin inhibitor.

Effect of Aerobic Training and Use of Nanomicelle Curcumin on Gene Expression of GPX, Cat, SOD and MDA Enzymes in Heart Tissue of Balb C Female Mice with Induced Breast Cancer in Treatment Phase with Doxorubicin

Introduction:Doxorubicin is a universal drug in treatment of all types of cancers, which is limited in its use due to various side effects in body tissues, so the present study investigated effect of aerobic exercise and use of curcumin nanomicelles on gene expression of the enzymes (GlutathionePeroxidase) GPX, (Catalase) Cat (Superoxidedismutase) SOD and (Malondialdehyde) MDA was investigated in the heart tissue of BalbC female rats with induced breast cancer in the treatment phase of doxorubicin.&#x0D; method: This research was practical, it was experimental in terms of control of variables and it was a laboratory in terms of place of implementation. Thirty-six BalbC mice were randomly divided into 6 groups (n=6): healthy, patient, doxorubicin patient, doxorubicin patient and aerobic exercise, doxorubicin patient and nanocurcumin supplement, and doxorubicin patient, aerobic exercise and supplementation. Breast cancer induction was done with MC4-L2 cells. Doxorubicin 2mg/kg was injected subcutaneously 6 times on days 1,7,14,21,28 and 35. Aerobic program consisted of 5 sessions per week for 42 days with an increase in the speed of the treadmill every two weeks, including 14, 16 and 18meters per minute and the use of nanocurcumin at a dose of 100mg/kg.The data collected with SPSS version16 and two-way analysis of variance and for the normality of the frequency distribution with skewness and non-parametric Kolmogorov-Smirnov test were performed with a significance level of P ≤ 0.05.&#x0D; Results: Six weeks of aerobic training had no effect on the expression of GPX, MDA and SOD genes in the target groups, but it significantly increased the expression of Catgene (P ≤ 0.05). The use of nanocurcurmin supplement for 6 weeks decreased the expression of MDA gene and significantly increased the expression of GPX, SOD and Catgenes. Six weeks of aerobic training along with nanocorcurmin supplementation significantly increased Cat gene expression (P≤0.05), but had no effect on GPX, MDA and SOD gene expression.&#x0D; Conclusion: Aerobic exercises and the use of nanocurcurmin supplement separately or at the same time can be effective in reducing the cardiac toxicity of doxorubicin in the patients with breast cancer.

Metabiotic extracted from Bifidobacterium bifidum modulates antioxidant capacity and inflammatory responses during peptic ulcer healing in male wistar rats: a preliminary study.

Peptic ulcer disease is a multifactorial disease that affects up to 10% of people. The use of natural product remedies has received much attention for its treatment. In this research, the healing effect of metabiotic extracted from Bifidobacterium bifidum was investigated. 45 male wistar rats were divided into 3 groups (Ctrl-, drug, and metabiotic), and stomach ulcers were induced by ethanol administration and treated by drug and metabiotic. The healing process was investigated on different days by histological analysis and qRT-PCR. The metabiotic increased IL-8 and PDGF expression and stimulated the recruitment of polymorphonuclear cells to the wound site. It caused a faster onset of the inflammation phase followed by the proliferation phase. The metabiotic increased the expression of SOD and GPx genes and the antioxidant capacity of the wound. The increase in EGF expression led to faster re-epithelization, which was evident in the wound closure process. Metabiotic extracted from B. bifidum is a promising candidate for the treatment of PUD. It causes a faster onset of the inflammation phase. Improving the antioxidant status of the wound, causes a faster resolution of inflammation, which leads to the acceleration of the wound-healing process.

α-Tocopherol Transfer Protein-Null Mice with Very Low α-Tocopherol Status Do Not Have an Enhanced Lipopolysaccharide-Induced Acute Inflammatory Response

BackgroundThe α-tocopherol transfer protein-null (Ttpa−/−) mouse model is a valuable tool for studying the molecular and functional consequences of vitamin E (α-tocopherol, αT) deficiency. Because αT has been associated with reduced oxidative stress and improved immune function, we hypothesized that depleted αT concentration would exacerbate LPS-induced acute inflammatory response in the brain and heart of Ttpa−/− mice fed a vitamin E deficient (VED) diet. ObjectivesThe objective was to investigate how extremely low αT status, followed by exposure to LPS, altered the acute inflammatory response to LPS in Ttpa−/− and wild-type (Ttpa+/+) mice. MethodsThree-week-old male Ttpa+/+ and Ttpa−/− littermates (n = 36/genotype) ingested a VED diet ad libitum for 4 wk. At week 7, mice received an intraperitoneal LPS (1 or 10 μg/mouse) or saline (control) injection and were killed 4 h postinjection. Brain and heart IL-6 protein concentrations and tissue and serum αT concentrations were measured via ELISA and HPLC with photodiode array detection, respectively. Hippocampal Il-6, Tnf, and Gpx1 gene expression were measured via reverse transcriptase-quantitative polymerase chain reaction, and blood immune cell profiles were measured via a hematology analyzer. ResultsαT accumulation in analyzed tissues and serum of Ttpa−/− mice was substantially lower than Ttpa+/+ mice. Circulating white blood cell concentration, particularly lymphocytes, were lower in all LPS groups compared with controls (P < 0.01). The 10 μg LPS groups had elevated IL-6 in the cerebellum and heart compared with controls, confirming an acute inflammatory response (P < 0.01). Hippocampal and heart Il-6 gene expression in the LPS-treated Ttpa−/− mice was upregulated in a dose-dependent manner (P < 0.05). ConclusionsThe 10 μg LPS dose enhanced inflammatory markers in the brain, heart, and serum in each genotype but the lower αT status in Ttpa−/− mice did not further impact the acute immune responses.

Potential roles of 4HNE-adducted protein in serum extracellular vesicles as an early indicator of oxidative response against doxorubicin-induced cardiomyopathy in rats

Late-onset cardiomyopathy is becoming more common among cancer survivors, particularly those who received doxorubicin (DOXO) treatment. However, few clinically available cardiac biomarkers can predict an unfavorable cardiac outcome before cell death. Extracellular vesicles (EVs) are emerging as biomarkers for cardiovascular diseases and others. This study aimed to measure dynamic 4-hydroxynonenal (4HNE)-adducted protein levels in rats treated chronically with DOXO and examine their link with oxidative stress, antioxidant gene expression in cardiac tissues, and cardiac function. Twenty-two male Wistar rats were randomly assigned to receive intraperitoneal injection of normal saline (n = 8) or DOXO (3 mg/kg, 6 doses, n = 14). Before and after therapy, serum EVs and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were determined. Tunable resistive pulse sensing was used to measure EV size and concentration. ELISA was used to assess 4HNE-adducted protein in EVs and cardiac tissues. Differential-display reverse transcription-PCR was used to quantitate cardiac Cat and Gpx1 gene expression. Potential correlations between 4HNE-adducted protein levels in EVs, cardiac oxidative stress, antioxidant gene expression, and cardiac function were determined. DOXO-treated rats showed more serum EV 4HNE-adducted protein than NSS-treated rats at day 9 and later endpoints, whereas NT-proBNP levels were not different between groups. Moreover, on day 9, surviving rats' EVs had higher levels of 4HNE-adducted protein, and these correlated positively with concentrations of heart tissue 4HNE adduction and copy numbers of Cat and Gpx1, while at endpoint correlated negatively with cardiac functions. Therefore, 4HNE-adducted protein in serum EVs could be an early, minimally invasive biomarker of the oxidative response and cardiac function in DOXO-induced cardiomyopathy.