Glutathione Peroxidase Enzyme Activities Research Articles

Integrated histopathology and transcriptome metabolome profiling reveal the toxicity mechanism of phenazine-1-carboxylic acid in zebrafish

Phenazine-1-carboxylic acid (PCA) is a new type of agrochemical used to prevent plant diseases, but its effects on aquatic organisms are unclear. To comprehensively assess the impacts of PCA for aquatic organisms and its associated environmental risks, this study investigated, taking zebrafish as the research object, the toxicological mechanism of PCA by means of optical microscopy, hematoxylin and eosin (HE) staining, ultrastructural observation, physiological and biochemical testing, transcriptome sequencing, metabolome analysis, fluorescence quantitative PCR and molecular simulation. The results indicated that PCA was detrimental to zebrafish embryos, larvae and adults, with LC50 values at 96 h of 3.9093 mg/L, 8.5075 mg/L, and 13.6388 mg/L, respectively. PCA caused abnormal spontaneous movement, slowed the heart rate, delayed hatching, shortened the body length, slowed growth, and caused malformations. PCA mainly affected the brain, liver, heart, and ovaries. PCA distorted cell morphology, damaged mitochondrial membranes, disintegrated mitochondrial ridges, and dissociated nuclear membranes. PCA inhibited the enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX), decreased the malondialdehyde (MDA) content and disrupted antioxidant effects. The results of omics studies confirmed that PCA interfered with the transcriptional and metabolic network of zebrafish, downregulating most genes and metabolites. PCA mainly affected functions related to mitochondrial steroids, lipids, sterols, oxidoreductase activity and pathways involving cofactors, steroids, porphyrin, cytochromes, which specifically bound to targets such as panx3, agmat, and ace2. PCA was moderately toxic to zebrafish, and its usage should be strictly controlled to reduce toxic effects on aquatic organisms. The results of this study provide a new insights for ecotoxicology research.

Effects of organic and inorganic selenium supplementation on frozen-thawed ram semen at two cooling periods.

The aim of this study was to evaluate the effects of different selenium compounds on the sperm quality of cryopreserved ram semen. Ejaculates from four rams, collected using an artificial vagina heated to 38°C, were individually evaluated. The approved ejaculates were pooled and diluted (1:1 v:v) in Tris-egg yolk extender (20%, v/v) and separated into two control groups, one cooled for 2h and the other for 4h. The pooled ejaculates at the two cooling periods were supplemented with two doses (0.5 and 1μg/mL) of organic selenium (ORG), and inorganic selenium (SeNa), each. The samples were packed in 0.25ml straws, at a concentration of 400 × 106 sperms/mL and stored in liquid nitrogen. The straws were thawed in a water bath at 37°C for 20s, and the samples were subjected to sperm kinetics evaluation by Computer Assisted Semen Analysis software. Sperm membrane integrity, acrosome morphology, and mitochondrial potential were assessed. In addition, oxidative stress markers reactive oxygen species (ROS), ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive species (TBARS), and glutathione peroxidase (GPx) enzyme activity) were also evaluated. No significant improvement was observed in the ram semen quality at the two cooling times. Supplementation of the freezing extender with 0.5μg/mL ORG, subjected to 4h cooling period, increased the sperm motility when compared with the control group at the same cooling time. In addition, the 0.5μg/mL SeNa group, under the 2h cooling period, showed an increase in sperm motility when compared to the control group at the same cooling period. Considering the importance of sperm motility as a fertility parameter, our study indicates that supplementation with ORG and SeNa can help improve the total motility of the cryopreserved ram semen.

Biochemical and molecular assessment of oxidative stress in fruit fly exposed to azo dye Brilliant Black PN.

Azo dyes are widely used in the food industry to prevent color loss during processing and storage of products. This study aimed to investigate the effect of a diazo dye Brilliant Black PN (E151) on oxidative stress-related parameters in fruit flies (Drosophila melanogaster) at biochemical and molecular levels. Third instar larvae were transferred to a medium containing the dye at different doses (1, 2.5, and 5mg/mL). Gene expression and activity of superoxide dismutase, catalase (CAT), glutathione peroxidase (GPX), and acetylcholinesterase (AChE) enzymes were determined in the heads of adult flies obtained from these larvae. In addition, the glutathione (GSH) and malondialdehyde levels were measured using spectrophotometric analysis. Mitochondrial DNA (mtDNA) copy number was also detected by real-time PCR. The results showed that treatment with 5mg/mL of the dye caused a decrease in both gene expression and enzyme activity of CAT and GPx. Moreover, the same dose of dye treatment decreased AChE activity, GSH level, and mtDNA copy number. As a result, Brilliant Black PN dye can trigger toxicity by altering the level and activity of oxidative stress-related biomarkers in a dose-dependent manner. Therefore, more comprehensive studies are needed to elucidate the side effect mechanism and toxicity of this dye.

How does warmer sea water change the sensitivity of a Mediterranean thermophilic coral after immune-stimulation?

Anthropogenic climate change is warming sea water worldwide, pushing the limits of tolerance for marine organisms and driving a decline in biodiversity. The risk of thermal anomalies has increased particularly in the Mediterranean region over the last 30 yrs, where intense warming has been identified as one of the main stressors in coastal regions. To determine the influence of warmer conditions on the immunity of an endemic Mediterranean coral species, different immune activity parameters were compared in response to elevated temperature (~ 28 °C) and the presence of a pathogen-associated molecular pattern—Escherichia coli lipopolysaccharide (LPS)—as an elicitor of the innate immune response of Astroides calycularis. Immune parameters, which included phenoloxidase-like, glutathione peroxidase, lysozyme-like, alkaline phosphatase, and esterase enzyme activity, were measured over time after LPS balneation (0-, 12-, 48-, and 120 h time point). All five enzymes demonstrated constant values under environmental conditions (~ 23 °C), indicating a constituent activity. LPS at environmental temperature induced significant upregulation immediately after exposure (0 h-time point), demonstrating an immune response to the pathogen elicitor. Under warmer conditions (~ 28 °C), constituent values increased over time, indicating a shift in the immune strategy to maintain homeostasis. However, warmer sea water, within the summer range experienced by this coral species, impaired the immune response to LPS, delaying it over time. These changes in immune strategy indicate that temperature affects coral immunity and, in thermophilic A. calycularis, results in an energy trade-off that could maintain its health-state through suboptimal conditions during multiple perturbations, such as summertime diseases.

The role of geraniol on hepatic ischemia-reperfusion injury model in rats.

Hepatic ischemia/reperfusion (I/R) injury is a significant clinical condition that can arise during liver resections, trauma, and shock. Geraniol, an isoterpene molecule commonly found in nature, possesses antioxidant and hepatoprotective properties. This study investigates the impact of geraniol on hepatic damage by inducing experimental liver I/R injury in rats. Twenty-eight male Wistar Albino rats weighing 350-400 g were utilized for this study. The rats were divided into four groups: control group, I/R group, 50 mg/kg geraniol+I/R group, and 100 mg/kg geraniol+I/R group. Ischemia times were set at 15 minutes with reperfusion times at 20 minutes. Ischemia commenced 15 minutes after geraniol administration. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactic acid were measured, along with superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity levels in liver tissues. Liver tissues were also examined histopathologically. It was observed that intraperitoneal administration of 50 mg/kg and 100 mg/kg geraniol significantly reduced AST, lactic acid, and tumor necrosis factor-alpha (TNF-α) levels. The serum ALT level decreased significantly in the 50 mg/kg group, whereas no significant decrease was found in the 100 mg/kg group. SOD and GPx enzyme activities were shown to increase significantly in the 100 mg/kg group. Although there was an increase in these enzyme levels in the 50 mg/kg group, it was not statistically significant. Similarly, CAT enzyme activity increased in both the 50 mg/kg and 100 mg/kg groups, but the increase was not significant. The Suzuki score significantly decreased in both the 50 mg/kg and 100 mg/kg groups. The study demonstrates that geraniol reduced hepatic damage both biochemically and histopathologically and increased antioxidant defense enzymes. These findings suggest that geraniol could be used to prevent hepatic I/R injury, provided it is corroborated by large-scale and comprehensive studies.

Evaluation of Oxidant/Antioxidant Markers, Cytokines, DNA Damage and Trace Mineral Levels in Goats Naturally Single and Co-Infected with Theileria ovis and Anaplasma ovis

The impact of co-infections with Theileria ovis and Anaplasma ovis on caprine health is very limited knowledge and is rarely documented in the literature. Türkiye is endemic for tick-borne diseases (TBDs), posing a risk of co-infections in goats. To evaluate the impact of single and co-infection with T. ovis and A. ovis on caprine health, four groups of goats were examined: healthy goats, goats infected with T. ovis, goats infected with A. ovis and goats co-infected with both species. Sera from blood samples was tested for oxidant/antioxidant markers [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (KAT), glutathione peroxidase (GPx), glutathione S-transferase (GST)], cytokines [interleukins (IL)-6, IL-1, tumor necrosis factor-α (TNF-α)], DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)] and trace minerals [( copper (Cu), zinc (Zn), manganese (Mn), selenium ( Se)]. MDA, 8-OHdG, TNF-α, IL-1 and IL-6 levels, CAT and GST enzyme activities were found to be significantly increased in both Theileria ovis and Anaplasma ovis single- and co-infections (P<0.05). In goats, single and co-infected with A. ovis showed a statistically significant increase in SOD enzyme activity compared to goats infected only with T. ovis (P<0.05). In goats co-infected with A. ovis and T. ovis, considerable decrease in GPx enzyme activity were observed (P<0.05). Zn and Se levels in single infected with A. ovis indicated a significant decrease. Also, Cu, Zn, and Se levels in co-infected animals decreased significantly (P<0.05). Significant increase in lipid peroxidation and antioxidant enzyme activity in goats with single and double infections indicates impaired erythrocyte membrane integrity due to oxidative stress. Moreover, increased proinflammatory cytokine concentrations in all groups indicate that a high degree of systemic inflammation is induced during parasitaemia.

Protective effect of 1, 8-cineole (eucalyptol) against lead-induced liver injury by ameliorating oxidative stress and inflammation and modulating TLR4/MyD88/NF-κB signaling.

This study was conducted to explore the impact of 1, 8-cineole (eucalyptol) on the biochemical, molecular, and histological changes caused by lead acetate in the liver of adult male Wistar rats. The research also investigated the potential involvement of the TLR4 signaling pathway in this effect. Rats were orally administered lead acetate (25 mg/kg-day) for 14 consecutive days and received 1, 8-cineole (100 mg/kg-day) during the same period. 1, 8-cineole prevented an increase in the malondialdehyde level, a decrease in the glutathione level, and a decrease in the activity of superoxide dismutase and glutathione peroxidase enzymes in the liver of rats treated with lead acetate. This monoterpene also prevented an increase in the expression of pro-inflammatory cytokines and significantly reduced the infiltration of inflammatory cells in the liver parenchyma. Additionally, 1, 8-cineole discouraged the increase in toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor kappa B (NF-κB) expression in the liver and stopped a rise in serum AST and ALT enzymes. 1, 8-cineole can prevent liver damage caused by lead acetate by reducing oxidative stress and inflammation. This hepatoprotection is probably achieved by inhibiting TLR4/MyD88/NF-κB signaling.

Synergistic interplay of redox homeostasis and polysaccharide synthesis promotes cotton fiber elongation.

Cell polarity is the foundation of cell development and tissue morphogenesis. The investigation of polarized growth provides opportunities to gain profound insights into morphogenesis and tissue functionality in organisms. Currently, there are still many mysteries surrounding the mechanisms that regulate polarized cell growth. Cotton fiber cells serve as an excellent model for studying polarized growth, and provide important clues for unraveling the molecular mechanisms, signaling pathways, and regulatory networks of polarized growth. In this study, we characterized two functional genes, GhMDHAR1AT/DT and GhDHAR2AT/DT with predominant expression during fiber elongation. Loss of function of both genes contributed to a significant increase in fiber length. Transcriptomic data revealed up-regulated expression of antioxidant genes in CRISPR mutant lines, along with delayed expression of secondary wall-related genes and temporally prolonged expression of primary wall-related genes. Experimental evidence demonstrated that the increase in GSH content and glutathione peroxidase (GPX) enzyme activity led to enhanced total antioxidant capacity (T-AOC), resulting in reduced H2O2 levels, which contributed to the extension of fiber elongation stage in CRISPR mutant lines. Moreover, the increased polysaccharide synthesis in CRISPR mutant lines was found to provide an abundant supply of raw materials for fiber cell wall elongation, suggesting that synergistic interplay between redox homeostasis and polysaccharide synthesis in fiber cells may facilitate cell wall remodeling and fiber elongation. This study provides valuable insights for deciphering the mechanisms of cell polarized growth and improving cotton fiber quality.

The effect of obesity on oxidative stress parameters in pregnant women

Objective: In recent years, there has been a growing public concern about obesity, since it is known to reduce fertility in women and increase the duration of conception. Maternal obesity is also related to adverse pregnancy outcomes affected by placental malfunction. Therefore, in this study, we aimed to compare levels of oxidative stress between obese women and women of normal weight in the second trimester.
 
 Method: We assessed lipid peroxidation by measuring the thiobarbituric acid reactive species (TBARS), as well as the antioxidant defense system by measuring the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) enzymes in 50 obese women (body mass index, BMI:36.60±4.95) and 51 women of normal weight (BMI:24.51±3.47).
 
 Results: Increased lipid peroxidation and SOD enzyme activity were determined in obese pregnant women when compared to women of normal weight. Also, we found a significantly positive correlation (r:0.286, p:0.0435) between BMI and TBARS level as well as a significantly negative correlation (r: -0.421, p:0.002) between TBARS level and SOD enzyme activity. No significant difference was observed between the two groups in CAT and GPx enzymes activities.
 
 Conclusion: Although increased SOD enzyme activity indicates that the antioxidant defense system is activated to deal with increased production of reactive oxygen species, maternal obesity is induced by oxidative stress via increased lipid peroxidation. Hence, maternal-obesity-induced oxidative stress in the second trimester should be followed up by clinicians since it may cause oxidative damage in the placenta during pregnancy.

Effect of temperature on growth, survival, and chronic stress responses of Arctic Grayling juveniles.

Arctic Grayling Thymallus arcticus are Holarctically distributed, with a single native population in the conterminous United States occurring in the Big Hole River, Montana, where water temperatures can fluctuate throughout the year from 8 to 18 °C. A gradual increase in mean water temperature has been reported in this river over the past 20 years due to riparian habitat changes and climate change effects. We hypothesized that exposing Arctic Grayling to higher temperatures would result in lower survival, decreased growth, and increased stress responses. Over a 144-day trial, Arctic Grayling juveniles were subjected to water temperatures ranging from 8-26 °C to measure the effects on growth, survival, gene expression and antioxidant enzyme activity. Fish growth increased with increasing water temperature up to 18 °C, beyond which survival was reduced. Fish did not survive at temperatures above 22 °C. In response to temperatures above 16 °C, a 3-fold and 1.5-fold increase in gene expression was observed for superoxide dismutase (SOD) and glutathione peroxidase (GPx), respectively, but no changes were seen in the ratio of Heat Shock Protein 70 (HSP70) and heat shock protein 90 (HSP90) expression. Enzyme activities of SOD and GPx also rose at temperatures above 16 °C, indicating heightened oxidative stress. Catalase (CAT) gene expression and enzyme activity decreased with rising temperatures, suggesting a preference for the GPx pathway, as GPx could also be providing help with lipid peroxidation. An increase of Thiobarbituric acid reactive substances (TBARS) was also recorded, which corresponded with rising temperatures. Our findings thus underscore the vulnerability of Arctic Grayling to minor changes in water temperature. Further increases in mean water temperature could significantly compromise survival of Arctic Grayling in the Big Hole River.

A Bimetallic Polymerization Network for Effective Increase in Labile Iron Pool and Robust Activation of cGAS/STING Induces Ferroptosis-Based Tumor Immunotherapy.

Due to the inherent low immunogenicity and immunosuppressive tumor microenvironment (TME) of malignant cancers, the clinical efficacy and application of tumor immunotherapy have been limited. Herein, a bimetallic drug-gene co-loading network (Cu/ZIF-8@U-104@siNFS1-HA) is developed that increased the intracellular labile iron pool (LIP) and enhanced the weakly acidic TME by co-suppressing the dual enzymatic activities of carbonic anhydrase IX (CA IX) and cysteine desulfurylase (NFS1), inducing a safe and efficient initial tumor immunogenic ferroptosis. During this process, Cu2+ is responsively released to deplete glutathione (GSH) and reduce the enzyme activity of glutathione peroxidase 4 (GPX4), achieving the co-inhibition of the three enzymes and further inducing lipid peroxidation (LPO). Additionally, the reactiveoxygenspecies (ROS) storm in target cells promoted the generation of large numbers of double-stranded DNA breaks. The presence of Zn2+ substantially increased the expression of cGAS/STING, which cooperated with ferroptosis to strengthen the immunogenic cell death (ICD) response and remodel the immunosuppressive TME. In brief, Cu/ZIF-8@U-104@siNFS1-HA linked ferroptosis with immunotherapy through multiple pathways, including the increase in LIP, regulation of pH, depletion of GSH/GPX4, and activation of STING, effectively inhibiting cancer growth and metastasis.

Effects of l-ascorbic acid on growth, non-specific immunity, antioxidant capacity, and intestinal and hepatopancreatic histology of red swamp crayfish, Procambarus clarkii

This study investigated the dietary effects of coated l-ascorbic acid (LA) on growth, feed utilization, survival, serum biochemical indices, immunity, antioxidant capacity, and intestinal and hepatopancreatic histology of the pre-adult red swamp crayfish. Four isoproteinous and isolipidic diets were formulated to contain several LA levels as 0, 1300, 1600, and 1900 mg/kg and designated as control (LA0), LA13, LA16, and LA19, respectively. However, the analyzed LA concentrations in diets were 0.00, 199.57, 360.45, and 487.50 mg/kg in LA0, LA13, LA16, and LA19, respectively. Triplicate treatments of crayfish (21.60 ± 0.14 g) were fed the test diets and reared in fiberglass tanks with a density of 20 individuals per each for eight weeks. Results revealed that all LA treatments had significantly enhanced growth performance compared to the control. Of interest, the LA16 treatment recorded the highest final tank biomass, biomass gain, total feed intake, condition factor, and muscle yield among the other treatments. The tank feed conversion ratio was significantly decreased in LA treatments compared to the control. Moreover, dietary LA16 and LA19 had significantly higher survival rates (93.3%) compared to (85.0%) in the LA0 group. All dietary doses of LA significantly increased serum parameters (total protein, albumin, globulin, lysozyme activity) and respiratory burst activity compared to the LA0 treatment. Dietary LA16 significantly boosted the hepatopancreatic antioxidant capacity, manifested by decreased malondialdehyde concentrations, increased catalase, superoxide dismutase, and glutathione peroxidase enzyme activities, and reduced glutathione content compared to the LA-free diet. A normal histoarchitecture of the hepatopancreatic tubules was found in all LA treatments except with some minor degenerative changes in the tubular lumen, and hepatopancreatic cells associated with enlarged nuclei were found in the LA19. However, normal intestinal histoarchitecture was found in all treatments with no recorded intestinal lesions. Of interest, the polynomial regression performed on the analyzed LA concentrations suggested that 380 mg/kg would be suitable to provide maximal biomass gain for pre-adult crayfish. In conclusion, results revealed that coated LA could enhance the growth, immunity, and antioxidant capacity of pre-adult red swamp crayfish, suggesting its potential as a functional and necessary micronutrient for crayfish diets.

Effect of in vitro supplementation of branched-chain amino acids on glutathione peroxidase enzyme activity and intracellular glutathione concentration in CACO-2 cells

Effect of in vitro supplementation of branched-chain amino acids on glutathione peroxidase enzyme activity and intracellular glutathione concentration in CACO-2 cells

Antioxidant Status in the Blood of Psychosocially Stressed Rats Treated with Honey

Abstract Linden honey represents a unique honey variety valued for its nutritional benefits, distinctive taste and aroma. Phenols, polyphenols, flavonoids, ascorbic acid and phenolic acids in honey have antioxidant activities. This study aimed to investigate the effects of linden honey on the activities of antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPx), as well as on the concentration of malondialdehyde (MDA) in individually housed animals. The investigated parameters were quantified using spectrophotometric method for determination of enzyme activities and MDA concentration in the blood. We found that treatment with linden honey in the socially isolated animals significantly increased the enzyme activities of CAT and GPx, and significantly decreased the concentration of MDA. The modulation of CAT and GPx activities in socially isolated animals treated with linden honey may be very important for understanding the role of honey in the capacity of antioxidant defense system to increase and maintain its stability in psychosocial stress conditions. Our results may be important in biomedical research for understanding the role of honey in the amelioration of oxidative stress.

The effects of different light spectrum on some oxidative stress parameters in male and female rats

The objective of this study was to investigate oxidative stress parameters in plasma, liver, and brain of Sprague Dawley rats grown under a compact fluorescent lamp with purple, blue, green, yellow, orange, red, and white. For this purpose, 56 male and 56 female rats were housed in standard cages under seven different light colors from weaning until puberty. Malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GPx) in plasma, liver, and brain were examined as oxidative stress parameters. Two factors which are gender and light were investigated regarding the main effects by Two-way ANOVA with the General Linear Model procedure. The different light spectrums had a significant impact on MDA, GSH and, GPx of plasma, liver, and brain (P<0.05). The red group resulted the highest in plasma, liver, and brain MDA. In addition, some of the examined parameters were different for the gender basis. The plasma GSH, the liver MDA, the liver and brain GPx were different in male and female rats (P<0.05). Only the liver GPx enzyme activity was higher in male rats, the other parameters in the female rats had a higher value. In conclusion, low-wavelength lights may be more useful for rats’ environments when compared to high wavelengths in manner oxidative stress. However, illumination is not the sole phenomenon for raising animals. Environmental demands may vary from time to time and even according to gender. Moreover, it may be useful for studies to be conducted by considering other lighting factors such as intensity and cycle.

Hepatoprotective Effects of Biochanin A on Thioacetamide-Induced Liver Cirrhosis in Experimental Rats.

The protective effect of biochanin A (BCA) on the histopathology, immunohistochemistry, and biochemistry of thioacetamide (TAA)-induced liver cirrhosis in vivo was investigated. There was a significant reduction in liver weight and hepatocyte propagation, with much lower cell injury in rat groups treated with BCA (25 mg/kg and 50 mg/kg) following a TAA induction. These groups had significantly lower levels of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA). The liver homogenates showed increased antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as decreased malondialdehyde (MDA) levels. The serum biomarkers associated with liver function, namely alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transaminase (GGT), returned to normal levels, comparable to those observed in both the normal control group and the reference control group. Taken together, the normal microanatomy of hepatocytes, the inhibition of PCNA and α-SMA, improved antioxidant enzymes (SOD, CAT, and GPx), and condensed MDA with repairs of liver biomarkers validated BCA's hepatoprotective effect.

Effects of Full-Spectrum Cannabis Oil with a Cannabidiol:Tetrahydrocannabinol 2:1 Ratio on the Mechanisms Involved in Hepatic Steatosis and Oxidative Stress in Rats Fed a Sucrose-Rich Diet

Introduction: This study aimed to analyze the effects of cannabis oil (cannabidiol:tetrahydrocannabinol [CBD:THC], 2:1 ratio) on the mechanisms involved in hepatic steatosis and oxidative stress in an experimental model of metabolic syndrome (MS) induced by a sucrose-rich diet (SRD). We hypothesized that noninvasive oral cannabis oil administration improves hepatic steatosis through a lower activity of lipogenic enzymes and an increase in carnitine palmitoyltransferase-1 (CPT-1) enzyme activity involved in the mitochondrial oxidation of fatty acids. Furthermore, cannabis oil ameliorates liver oxidative stress through the regulation of the main regulatory factors involved, nuclear factor erythroid 2 (NrF2) and nuclear factor-kB (NF-κB) p65. For testing this hypothesize, a relevant experimental model of MS was induced by feeding rats with a SRD for 3 weeks. Methods: Male Wistar rats were fed the following diets for 3 weeks: reference diet: standard commercial laboratory diet, SRD, and SRD + cannabis oil: noninvasive oral administration of 1 mg/kg body weight cannabis oil daily. The full-spectrum cannabis oil presents a total cannabinoid CBD:THC 2:1 ratio. Serum glucose, triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (AP), N-arachidonoylethanolamine or anandamide and 2-arachidonoylglycerol endocannabinoids levels, thiobarbituric acid reactive substance (TBARS) levels, and non-enzymatic antioxidant capacity (ferric ion-reducing antioxidant power [FRAP]) were evaluated. In the liver tissue: histology, nonalcoholic fatty liver disease activity score (NAS), triglycerides and cholesterol content, lipogenic enzyme activities (fatty acid synthase, acetyl-CoA carboxylase, malic enzyme, and glucose-6-phosphate dehydrogenase), enzyme related to mitochondrial fatty acid oxidation (CPT-1), reactive oxygen species, TBARS, FRAP, glutathione, catalase, glutathione peroxidase, and glutathione reductase enzyme activities. 4-hydroxynonenal, NrF2, and NF-κB p65 levels were analyzed by immunohistochemistry. Results: The results showed that SRD-fed rats developed dyslipidemia, liver damage, hepatic steatosis (increase of key enzymes related to the novo fatty acid synthesis and decrease of key enzyme related to mitochondrial fatty acid oxidation), lipid peroxidation, and oxidative stress. Hepatic NrF2 expression was significantly decreased and NF-κB p65 expression was increased. Cannabis oil administration improved dyslipidemia, liver damage, hepatic steatosis, lipid peroxidation (improving enzymes involved in lipid metabolism), and oxidative stress. In the liver tissue, NrF2 expression increased, and NF-κB p65 expression was reduced. Conclusion: The present study revealed new aspects of liver damage and steatosis, lipid peroxidation, and oxidative stress in dyslipidemic insulin-resistant SRD-fed rats. We demonstrated new properties and molecular mechanisms of cannabis oil (CBD:THC, 2:1 ratio) on lipotoxicity and hepatic oxidative stress in an experimental model of MS.

Dietary inclusion of Pediococcus acidilactici probiotic promoted the growth indices, hemato-biochemical indices, enzymatic profile, intestinal and liver histomorphology, and resistance of Nile Tilapia against Aspergillus flavus

This study investigated the effect of probiotic Pediococcus acidilactici CNCM I-4622 on the water quality, growth indices, hematological parameters, biochemical profile, innate immunity (lysozyme (LYZ) and immunoglobulin M (IgM)), and antioxidant (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX)) and digestive enzymes activity, with reference to the intestinal and liver histology of Nile Tilapia (Oreochromis niloticus), as well as disease resistance against Aspergillus flavus. A field trial was carried out for 56 days in which Nile tilapia fingerlings (4.0 ± 0.3 g) were randomly distributed into three replicate concrete ponds which were subdivided into four treatment groups, receiving P. acidilactici CNCM I-4622 at 0 (T0), 2.0 (T1), 2.5 (T2), and 3.0 (T3) g/kg diet, respectively. The obtained results revealed a significant amelioration in growth, feed utilization, body composition, and blood profiles, including erythrocytes and leukocyte counts, hemoglobin, and hematocrit concentration in the probiotics-treated groups compared to the control group. Dietary P. acidilactici at 2.5 and 3 g/kg diets enhanced the digestive enzymes (amylase, lipase, and protease) relative to the control group (p < 0.05). Biochemical parameters (total protein and albumin levels, and globulin) were notably increased, meanwhile, total cholesterol and triglycerides were significantly decreased in T3 supplemented group with a marked decrease in the levels of AST and ALT. Nevertheless, the serum activity of SOD, CAT, and GPX enzymes as well as LYZ and IgM were increased by P. acidilactici at 2.5 and 3 g/kg relative to the control group (p < 0.05). Also, a markedly increased length of the intestinal villi was prominent in treated fish with P. acidilactici at 2.5 and 3 g/kg. Feeding P. acidilactici at 3 g/kg significantly decreased the cumulative mortalities after the A. flavus challenge. In conclusion, our results presented the beneficial effects of P. acidilactici as a potent probiotic on growth indices, feed utilization, antioxidant properties, gut and liver health, and fungal resistance of Nile tilapia.

Glycyrrhizin alleviates varicellovirus bovinealpha 1-induced oxidative stress, inflammation, and apoptosis in MDBK cells by inhibiting NF-κB/NLRP3 axis through the Nrf2 signalling pathway.

Varicellovirus bovinealpha 1 (BoAHV-1) is one of the crucial pathogens of bovine respiratory diseases, and its pathogenic mechanism involves oxidative stress, inflammation response, and apoptosis. Glycyrrhizin (GLY) possesses powerful antiviral, antioxidant, anti-inflammatory, and anti-apoptotic bioactivities. However, the anti-BoAHV-1 activity of GLY and its role in BoAHV-1-induced oxidative stress, inflammation, and apoptosis remain unclear. Therefore, the current study investigated the anti-BoAHV-1 effect of GLY and its ability to alleviate BoAHV-1-induced oxidative stress, inflammation, and apoptosis using an in vitro model (MDBK cells). Our results showed that BoAHV-1 titers significantly increased in MDBK cells after infection, and GLY reduced the BoAHV-1 titers in MDBK cells exposed to it. Furthermore, Interleukin (IL)-1β, IL-8, tumor necrosis factor (TNF)-α, phosphorylated NF-κB p65 (p-NF-κB p65), the NLR pyrin domain containing 3 (NLRP3), Caspase-1, and Cleaved Caspase-3 levels were significantly upregulated when MDBK cells were challenged with BoAHV-1. In BAY 11-7085 (a specific NF-κB inhibitor) treated MDBK cells, IL-1β, IL-8, TNF-α, p-NF-κB p65, NLRP3, Caspase-1, and Cleaved Caspase-3 levels were downregulated. Notably, GLY treatment had the same trend as the BAY 11-7085 treatment. Thus, these results suggested that GLY exerted anti-inflammatory and anti-apoptotic activities by blocking NF-κB/NLRP3 axis. In addition, after BoAHV-1 infection, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and p-NF-κB p65 and apoptosis rate were increased, and catalase (CAT) and glutathione peroxidase (GSH-Px) enzyme activities, as well as NF-E2-related nuclear factor erythroid-2 (Nrf2) protein expression were repressed. Compared with BoAHV-1-infected MDBK cells, GLY treatment significantly downregulated intracellular ROS, MDA, and p-NF-κB p65 levels and apoptotic rates and significantly increased intracellular CAT and GSH-Px enzyme activities and Nrf2 expression. Additionally, ML385 (a specific Nrf2 inhibitor) abolished the enhancing effect of GLY on Nrf2 and the attenuating effect on ROS, p-NF-κB p65, and apoptosis. These results suggested that GLY had an anti-BoAHV-1 effect and could mitigate BoAHV-1-induced oxidative stress, inflammation, and apoptosis by activating the Nrf2 signalling and restraining NF-κB/NLRP3 axis.

Vitamin D: An effective therapy against methotrexateinduced cardiotoxicity

Purpose: To determine the potential cardioprotective effect of vitamin D (VD) against methotrexate (MTX) induced cardiotoxicity.Methods: A total of thirty-five (35) rats were randomly assigned to five equal groups. Control groupreceived no treatment; MTX group received intraperitoneal (IP) injection of MTX in a single dose of 20 mg/kg on day 8; VD group received 200 IU/kg VD daily dissolved in sunflower oil orally; sunflower oil (SO) group received 1 mL/kg/day SO orally; MTX + VD group received a single dose of MTX (20 mg/kg, IP) on day 8 and VD (200 IU/kg, orally) for 21 days. Myocardial tissue samples were harvested and used for clinical chemistry, histopathological, and ultrastructural evaluation.Results: Histopathological damage in MTX group was more severe than in control group under both light and electron microscopy. Expression of transient receptor potential melastatin 2 (TRPM2) and caspase-3 markers was significantly higher in MTX group (p &lt; 0.05). Glutathione peroxidase (GSH-Px) enzyme activity in cardiac tissue was lower in MTX group, whereas malondialdehyde (MDA) levels increased significantly (p &lt; 0.05). In MTX + VD group, VD treatment alleviated histopathological damage and significantly lowered TRPM2 and caspase-3 expressions (p &lt; 0.05). Vitamin D also reduced tissue MDA levels, and increased GSH-Px activity albeit non-significantly (p &gt; 0.05),Conclusion: These findings suggest that VD exerts an ameliorative effect on MTX-induced cardiotoxicity in rats. Therefore, TRPM2 channel affords a novel therapeutic approach for treatment of diseases related to chemotherapy-induced oxidative stress.