GSH) And Glutathione Peroxidase Research Articles

Fucoidan from Apostichopus japonicus ameliorates alcoholic liver disease by regulating gut-liver axis homeostasis

Long-term and excessive alcohol consumption can lead to the development of alcoholic liver disease (ALD), characterized by oxidative damage, intestinal barrier injury, and disruption of intestinal microbiota. In this study, we extracted fucoidan (Aj-FUC) from Apostichopus japonicus using enzymatic methods and characterized its structure. The ALD model was established in male Balb/c mice using 56° Baijiu, with silymarin as a positive control. Mice were orally administered 100 mg/kg·bw and 300 mg/kg·bw of Aj-FUC for 28 days to evaluate its effects on liver injury in ALD mice and explore its potential role in modulating the gut-liver axis. The results showed significant improvements in histopathological changes and liver disease in the Aj-FUC group. Aj-FUC treatment significantly increased the levels of glutathione (GSH) and glutathione peroxidase (GSH-Px) while weakly reduced the elevation of malondialdehyde (MDA) induced by ALD. It also regulated the Nrf2/HO-1 signaling pathway, collectively alleviating hepatic oxidative stress. Aj-FUC intervention upregulated the expression of ZO-1 and Occludin, thus contributing to repair the intestinal barrier. Additionally, Aj-FUC increased the content of short-chain fatty acids (SCFAs) and regulated the imbalance in gut microbiota. These results suggested that Aj-FUC alleviates ALD by modulating the gut-liver axis homeostasis. It may prove to be a useful dietary supplement in the treatment of alcoholic liver damage.

Green synthesis and characterization of polyphenol-coated magnesium-substituted manganese ferrite nanoparticles: Antibacterial and antioxidant properties

Magnesium-substituted manganese ferrite (Mn0.9Mg0.1Fe2O4) nanoparticles were obtained through a wet chemical method and coated with green-extracted polyphenol from Punica granatum peel. The obtained spinel nanocomposite was fully characterized. The X-ray diffraction pattern revealed a single phase with an average crystalline size of 3.33–8.74 nm, confirming the cubic-spinel structure. The FESEM micrograph showed a quasi-spherical shape with nearly uniform particles, indicating mild agglomeration. The mean size of the Mn0.9Mg0.1Fe2O4 was 13.66 nm with a standard deviation of 2.05. The BET isotherms indicated a surface area of 85.45 m2/g. The basic groups attached to the external surface of Mg-doped spinel ferrite were discovered. The resulted superparamagnetic modified doped-nanoferrite particles showed antibacterial activity as well as antioxidant efficiency through studying Catalase (CAT), Glutathione (GSH), and Glutathione Peroxidase (GSH-Px) parameters. The outcomes highlight the promising potential of polyphenol-functionalized Mn0.9Mg0.1Fe2O4 magnetite nanosized particles for the development of novel anti-biofilm agents.

H2O2-Induced Oxidative Stress Responses in Eriocheir sinensis: Antioxidant Defense and Immune Gene Expression Dynamics.

Eriocheir sinensis, a key species in China's freshwater aquaculture, is threatened by various diseases, which were verified to be closely associated with oxidative stress. This study aimed to investigate the response of E. sinensis to hydrogen peroxide (H2O2)-induced oxidative stress to understand the biological processes behind these diseases. Crabs were exposed to different concentrations of H2O2 and their antioxidant enzyme activities and gene expressions for defense and immunity were measured. Results showed that activities of antioxidant enzymes-specificallysuperoxide dismutase (SOD), catalase (CAT), total antioxidant capacity(T-AOC), glutathione (GSH), and glutathione peroxidase (GSH-Px)-varied with exposure concentration and duration, initially increasing then decreasing. Notably, SOD, GSH-Px, and T-AOC activities dropped below control levels at 96 h. Concurrently, oxidative damage markers, including malondialdehyde (MDA), H2O2, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, increased with exposure duration. The mRNA expression of SOD, CAT, and GSH-Px also showed an initial increase followed by a decrease, peaking at 72 h. The upregulation of phenoloxidaseloxidase (proPO) and peroxinectin (PX) was also detected, but proPO was suppressed under high levels of H2O2. Heat shock protein 70 (HSP70) expression gradually increased with higher H2O2 concentrations, whereas induced nitrogen monoxide synthase (iNOS) was upregulated but decreased at 96 h. These findings emphasize H2O2's significant impact on the crab's oxidative and immune responses, highlighting the importance of understanding cellular stress responses for disease prevention and therapy development.

Sinigrin improves cerebral ischaemia-reperfusion injury by inhibiting the TLR4 pathway-mediated oxidative stress.

Cerebral ischaemia-reperfusion (CIR) injury occurs in stroke patients after the restoration of cerebral perfusion. Sinigrin, a phytochemical found in cruciferous vegetables, exhibits strong antioxidant activity. This study investigated the role of sinigrin in oxidative stress using a CIR injury model. The effects of sinigrin were studied in middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-injured SH-SY5Y cells. Sinigrin treatment improved brain injury and neurological deficits induced by MCAO surgery in rats. Sinigrin inhibited apoptosis in brain tissues and SH-SY5Y cells following OGD/R induction. Additionally, sinigrin elevated the levels of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) while reducing malondialdehyde (MDA) levels. Furthermore, sinigrin inhibited the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signalling pathway. The anti-apoptotic and antioxidant activities of sinigrin in OGD/R-injured SH-SY5Y cells were reversed by TLR4 overexpression. In conclusion, sinigrin inhibits oxidative stress in CIR injury by suppressing the TLR4/MyD88 signalling pathway.

Dietary Supplementation of Chlorella vulgaris Effectively Enhanced the Intestinal Antioxidant Capacity and Immune Status of Micropterus salmoides.

An M. salmoides fish meal diet was supplemented with 0 (CHL0, Control), 38 (CHL38), 76 (CHL76), 114 (CHL114), and 152 (CHL152) mg/kg C. vulgaris for 60 days, and their serum and intestinal samples were analyzed. The results showed that the albumin (ALB) and total protein (TP) contents were observably enhanced in the CHL76 group compared with the Control group. The intestinal glutathione (GSH) and glutathione peroxidase (GSH-Px) contents were enhanced significantly in the CHL76 group, while the total antioxidant capacity (T-AOC) was enhanced in the CHL38 group, compared with the Control group. However, supplementation of >76 g/kg C. vulgaris significantly inhibited the superoxide dismutase (SOD) activity in the intestines of M. salmoides. Moreover, the malondialdehyde (MDA) content was observably dropped in the CHL-supplemented groups compared with the Control group. Transcriptome analysis of the CHL76 and Control groups displayed a total of 1384 differentially expressed genes (DEGs). KEGG analysis revealed that these DEGs were enriched in apoptosis, cytokine-cytokine receptor interaction, tight junction (TJ), and phagosome signaling pathways, which were associated with improved intestinal immunity in the CHL76 group. Additionally, the DEGs enriched in the above pathways were also correlated with the antioxidant parameters, such as catalase (CAT), GSH, GSH-Px, SOD, T-AOC, and MDA. Therefore, our study found that dietary supplementation of C. vulgaris effectively enhanced the intestinal antioxidant capacity of M. salmoides by increasing antioxidant enzyme activity and decreasing MDA content. Additionally, dietary supplementation of C. vulgaris improved the intestinal immune status of M. salmoides by reducing proapoptotic and proinflammatory factors, increasing intestinal TJs- and phagosome-related genes expressions, and increasing the serum ALB and TP contents. Lastly, quadratic regression analysis of the serum biochemical indices (ALB and TP) and intestinal antioxidant parameters (GSH-Px and GSH) revealed that the optimal supplemental level of C. vulgaris in the M. salmoides diet was 58.25-77.7 g/kg.

The Impacts of Dietary Curcumin on Innate Immune Responses and Antioxidant Status in Greater Amberjack (Seriola dumerili) under Ammonia Stress

In this study, we investigated the effect of dietary curcumin on non-specific immune responses and antioxidative ability in Seriola dumerili under ammonia stress and post-recovery. Three diets were prepared to contain 0, 75, and 150 mg/kg of curcumin. A total of 225 greater amberjack (initial weight: 100.90 ± 0.03 g) were distributed into nine cylindrical tanks, constituting an experimental design with three treatments and three replicates. After 56 days of feeding, plasma, intestinal, and hepatic enzyme activities were evaluated. Then, an acute ammonia challenge experiment was conducted. Ten fish per tank were subjected to acute ammonia stress (total ammonia-N: 1000 mg/L) for eight minutes followed by six minutes of recovery. The results indicated that dietary curcumin significantly promoted intestinal and hepatic alkaline phosphatase (ALP) and acid phosphatase (ACP) levels as well as hepatic antioxidative enzymes such as superoxide dismutase (SOD), total antioxidant capacity (T-AOC), reduced glutathione (GSH), and glutathione peroxidase (GSH-Px) of greater amberjack. In addition, curcumin addition improved the activities of antioxidant enzymes, such as SOD, T-AOC, GSH, GSH-Px, and catalase (CAT), and reduced malondialdehyde (MDA) content in liver, spleen, head kidney, and brain tissues after post-recovery. The indexes related to immunity and antioxidant enzymes in the liver, gill, and spleen rose again to some extent, but they showed the worst recovery ability in the head kidney and brain tissue samples. These results indicate that dietary curcumin supplementation could increase non-specific immune responses, antioxidant ability, and enhance resistance to high ammonia stress in juvenile S. dumerili.

Deneysel Epileptik Nöbet Modelinde, Artemisinin'in Fare Kalp ve Akciğer Dokularında Oksidatif Stress Belirteçleri Üzerine Etkisi.

Aim: The current study investigated the effects of artemisinin on the heart and lung tissue against pentylenetetrazol-induced seizures in mice. For this purpose, malondialdehyde (MDA), advanced oxidation protein products (AOPP), Catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels were evaluated in both tissue homogenates.Material and Method: Swiss albino male mice (n=42) were used in the experiment. Animals were divided into six groups; Control (C), pentylenetetrazol (PTZ), valproate 100 mg/kg (VPA), artemisinin 30 mg/kg (ARS)+PTZ, ARS 60 mg/kg+PTZ, ARS 120 mg/kg+PTZ. On the 26th day of the experiment, the mice were sacrificed and the samples were kept at -80 0C for biochemical analysis.Results: There were significant differences in the five biochemical parameters analyzed in heart and lung tissues. Heart and lung MDA levels of the PTZ group were found to be significantly higher than the C and ARS-60 groups (p<0.05). Heart and lung MDA levels of the PTZ group were found to be significantly higher than the C and ARS-60 groups. Likewise, heart AOPP levels decreased significantly in the VPA and ARS-60 groups compared to the PTZ group (p<0.05). There was no significant difference between the groups in terms of lung AOPP levels (p>0.05). Heart CAT and GSH levels were decreased in the PTZ group compared to the other groups. However, in terms of Lung CAT levels, the PTZ group had the highest value compared to the other groups, while it had the lowest value in terms of GSH level. The GSH-Px level did not differ significantly between the groups in heart tissue (p>0.05). The lung GSH-Px level was significantly increased in the ARS-30 group when compared to the PTZ group (p<0.05).Conclusion: Consequently ARS treatment can inhibit PTZ-induced oxidative stress in peripheral tissues. In addition, ARS may provide improvements in decreased antioxidant enzymes. ARS may contribute to the antioxidant defense system.

Effects of Different Calorie Restriction Protocols on Oxidative Stress Parameters in a Transgenic Mouse Model of Breast Cancer.

Aging and diseases related to aging, such as cancer, have been linked to oxidative stress. On the other hand, calorie restriction (CR) is one of the most effective interventions to slow down aging and prevent a variety of diseases such as cancer in preclinical models. CR has also been reported to modify oxidative stress. The aim of this study was to investigate the effects of different CR protocols and aging on oxidative stress parameters in the MMTV-TGF-α breast cancer mouse model in a cross-sectional study. Female mice were randomly enrolled in three groups: ad libitum (AL), chronic calorie restriction (CCR, 15% CR) or intermittent calorie restriction (ICR, three weeks AL followed by one week 60% CR in cyclic periods) starting at the age of 10 weeks until 81/82 weeks of age. Liver samples were analyzed for malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels. At week 49/50, the GSH level increased significantly in the CCR group compared to the AL and ICR-R groups which had higher mammary tumor (MT) incidence rates. Additionally, liver MDA levels in ICR groups were significantly increased, while aging led to decreased CAT and SOD activities in all CR groups. The application of different CR protocols did not have any significant effect on MDA, CAT, and SOD parameters in the liver at week 81/82. These results suggest that although GSH may interfere with MT development at the systemic level, many of the oxidative stress parameters may have more local effects on tumor development than the systemic effects.

Blood Coral Polysaccharide Helps Prevent D-Gal/LPS-Induced Acute Liver Failure in Mice

ObjectiveThe liver protection of blood coral polysaccharide (BCP) was investigated.Materials and MethodsWe evaluated the effect of BCP on liver pathology, liver function, oxidation and inflammation-related indicators of D-Gal/LPS-induced acute liver failure (ALF) mice in vivo.ResultsLiver index and liver pathology observation in mice showed that BCP could inhibit liver tissue swelling and hemorrhage, hepatocyte damage, and inflammatory infiltration in ALF. Serum liver function results showed that BCP effectively inhibits the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), total bilirubin (TBil), alkaline phosphatase (AKP), myeloperoxidase (MPO). High dose-blood coral polysaccharide (H-BCP) was better than silymarin. Serum antioxidant and immune results showed that BCP increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px), and inhibited the levels of malondialdehyde (MDA) and nitric oxide (NO). Also, BCP increased immunoglobulins G (IgG) and A (IgA) levels, thereby enhancing humoral immunity. Liver anti-inflammatory ELISA results showed that BCP reduced the levels of interleukin (IL)-6, IL-1β, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, and enhanced the level of anti-inflammatory factor IL-10. H-BCP was the most effective treatment. Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) of liver tissues confirmed that BCP increases the relative expression levels of antioxidant and anti-inflammatory-related cuprozinc superoxide dismutase (Cu/Zn-SOD, SOD1), manganese superoxide dismutase (Mn-SOD, SOD2), CAT, GSH, GSH-Px, and IL-10. In contrast, it inhibits inflammation-related genes IL-6, IL-1β, IL-17, TNF-α, IFN-γ, inducible nitric oxide synthase (iNOS, NOS2), and cyclooxygenase (COX)-2. In addition, BCP also inhibits the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and enhance B-cell inhibitor-α (IκB-α) gene relative expression in the liver, which may be related to NF-κB pathway inhibition.ConclusionBCP prevents D-Gal/LPS-induced ALF in mice, and its effect is concentration dependent.

Arsenic trioxide nanoparticles carrying miRNA-499 agonist activate PI3K/Akt signaling pathway by targeting Bak1 gene to reverse myocardial ischemia reperfusion injury

We evaluated miRNA-499′s effect on myocardial ischemia reperfusion (IR) injury. Serum Creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels, myocardial infarction area, miRNA-499, Bak1, PI3K, Akt Bcl-2, and Bax protein expressions were analyzed. CK levels in sham operation group were lowest after ischemia, while IR and negative control groups were highest, followed by the miR-499 group. IR and negative control groups showed highest MDA level, and lowest SOD, GSH and GSH-Px, followed by the miR-499 group. The IR group and negative control group showed significantly more infarct area than that of miR-499 group (p< 0.05). The lowest levels of Bak1, PI3K and Akt proteins were found in sham operation and miR-499 group, and the opposite was found in IR group (p< 0.05). Bcl-2 and Bax level expressions in sham-operation group and miR-499 group were lowest (p<0.05). Bak1 is a target for miR-499, and fluorescence intensity of mutant plasmid was increased (p< 0.05). In conclusion, miRNA-499 specifically binds to the target gene Bak1 and down-regulates Bak1 gene to activate the PI3K/Akt signaling pathway, therefore inhibiting myocardial apoptosis and ultimately ameliorating myocardial IR injury.

Chitosan-Coated Selenium Nanoparticles Attenuate PRRSV Replication and ROS/JNK-Mediated Apoptosis in vitro.

IntroductionPorcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that causes significant economic losses to the global swine industry. Selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. This study aimed to investigate the inhibitory effect of chitosan-coated SeNPs (CS-SeNPs) on PRRSV replication.MethodsIn this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 μM). Subsequently, the concentrations of hydrogen peroxide (H2O2) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, and nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID50, and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot.ResultsThe results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H2O2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The increase in apoptosis rates induced by r-PRRSV-EGFP infection was significantly decreased by CS-SeNPs inoculation through inhibiting ROS generation, JNK phosphorylation levels, and cleavage of caspase-3 and PARP mainly at 48 hpi.ConclusionThese results demonstrated that CS-SeNPs suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication, which suggested the potential antiviral activity of CS-SeNPs that deserves further investigation for clinical applications.

Protective Effect of Dandelion Leaf Water Extracts on APAP-Induced Liver Injury in Rats and Its Mechanism.

with the advent of a large number of drugs in recent years and the aggravation of human aging, drug-induced liver injury is increasing year by year. The protective effect of dandelion extract on acetaminophen (APAP) - induced drug-induced liver injury in rats and its specific mechanism was studied by in vitro cell culture. For this aim,twenty healthy SD rats with the same physiological status were divided into model group and normal group, with 10 rats in each group. The drug-induced liver injury model was made by intragastric administration of 1 g/kg APAP for 14 days. The liver function lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were detected to verify the success of the model. After that, the liver tissues were aseptically isolated from the normal group and APAP model group, and the primary hepatocytes were cultured. They were divided into control group (control), liver injury model group (model), medium-dose dandelion extract group (1mm dlwe) and high dose dandelion extract group (2mm dlwe). The cell proliferation activity was detected by CCK-8 cell proliferation activity kit. Cell samples were collected at 72 hours to detect the contents of AST and ALT in cell supernatant. The contents of oxidative stress-activated oxygen (ROS), reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) were detected by colorimetry, and the apoptosis was detected by flow cytometry. Inflammatory factors, key genes of liver injury, drug metabolic enzymes cytochrome P450 2E1 (CYP2E1), mitogen-activated protein kinase (MAPK) and nuclear transcription factors were detected by RT-PCR- κ B (NF- κ B) P65 signaling pathway-related gene expression level. Finally, the expression of CYP2E1, MAPK and NF-kB signaling pathwayswere analyzed by Western blot. Results showed thatSerum ast, ALT and LDH increased (P<0.05), suggesting that the liver injury model was successful. The hepatocytes in the normal group were oval, flat, evenly distributed and well adhered to the wall. The liver injury model group had more suspended cells, pseudopodia, polygonal and poor growth state. The cells in the medium-dose dandelion extract group (1mm dlwe) and high dose dandelion extract group (2mm dlwe) adhered well, mostly oval, similar to the normal group and grew well. CCK8 found that the cells in the model group decreased significantly, the proliferation activity decreased significantly, the ast, alt, LDH and ROS in the cell supernatant of the model group increased compared with other groups (P<0.05), and the contents of GSH and GSH PX decreased (P < 0.05). Apoptotic cells in the model group increased, and TNF in the model group-α, COX-2, CYP2E1, MAPK, JNK and NF KB p65 increased (P < 0.05). CYP2E1, MAPK and NF KB p65 increased in the model group (P < 0.05).

Folic acid alleviates lead acetate-mediated cardiotoxicity by down-regulating the expression levels of Nrf2, HO-1, GRP78, and CHOP proteins.

The purpose of this study was to explore the interventional effects of folic acid on the heart damage caused by lead acetate exposure. Twenty-four 60-day-old male Sprague-Dawley (SD) rats were randomly divided into 4 groups with 6 rats in each group. The control group (C group) was normal rats; the lead exposure group (L group) rats drank 0.2% lead acetate solution freely for 14days. The rats in the intervention group (T group) were given 0.2% lead acetate solution for 14days, respectively, and 0.4mg/kg BW folic acid solution was given to the rats by gavage on the 7th day of lead administration. The rats in the folic acid group (group E) were given 0.4mg/kg BW folic acid solution by gavage. To weigh rat body weight and heart weight, calculate heart index, and observe the expression level of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase 1(HO-1), glucose-regulated protein 78/binding immunoglobulin protein (GRP78), and C/EBP-homologous protein (CHOP) by immunofluorescence method. The results showed that compared with group C, serum lead levels in group L and T were significantly increased (P < 0.05); superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX) levels in group L were significantly decreased (P < 0.05), and malondialdehyde (MDA) content was significantly higher increased (P < 0.05), and the GSH-PX content in group T were significantly increased in group L (P < 0.05), and the MDA content in group T was significantly lower than that in group L (P < 0.05). Compared with group C, the expression of Nrf2, HO-1, GRP78, and CHOP in group L increased significantly, and the difference was statistically significant (P < 0.05). Compared with the L group, the expression of Nrf2, HO-1, GRP78, and CHOP in the T group was reduced. Therefore, folic acid has a certain protective effect on the oxidative damage of lead-exposed rat heart tissue. Lead exposure will increase ROS, NO, MDA, and other oxidizing substances and reduce the level of GSH, SOD, CAT, GPx, and other antioxidant factors, which will lead to cardiac hypertrophy, cardiac index increase, oxidative stress, Nrf2, and HO-1. The expression of stress-related proteins such as GRP78 and CHOP also increased, leading to cardiomyocyte apoptosis. After a folic acid intervention, these changes can be significantly reversed.

Evodiamine attenuates cadmium-induced nephrotoxicity through activation of Nrf2/HO-1 pathway

Purpose: To investigate the protective role of evodiamine, a naturally occurring anti-inflammatory, antioxidant, and anti-apoptotic compound, against cadmium-induced cytotoxicity in proximal tubular cells (human kidney 2; HK-2).&#x0D; Methods: HK-2 cells were treated with different concentrations of evodiamine (5, 20, 50 μM) for 2 h and then incubated with 40 μM cadmium chloride for another 24 h. Cell viability and apoptosis were evaluated using thiazolyl blue tetrazolium bromide (MTT) and flow cytometry, respectively. Oxidative stress was assayed by measuring the levels of malonaldehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-PX).&#x0D; Results: Cadmium chloride treatment in HK-2 cells significantly reduced cell viability (p &lt; 0.01) and increased apoptosis compared to the control. Evodiamine pretreatment attenuated the cadmium chloride-provoked decrease in cell viability and increase in apoptosis. Evodiamine also decreased expression of cleaved caspase-3 and cleaved caspase-9 in HK-2 cells. Cadmium chloride exposure provoked kidney injury, as evidenced by increased MDA levels and decreased SOD, GSH, and GSH-PX levels. Pretreatment with evodiamine ameliorated kidney injury, as shown by decreased MDA expression and increased SOD, GSH, and GSH-PX expression. Evodiamine exposure significantly enhanced protein expression of nuclear factor erythropoietin-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1).&#x0D; Conclusion: Evodiamine exerts an anti-apoptotic and anti-oxidative effect against cadmium chloride-induced nephrotoxicity via Nrf2/HO-1 pathway activation. These findings represent a potential therapeutic strategy for cadmium-provoked nephrotoxicity.

Protective Effects of Honey-Processed Astragalus on Liver Injury and Gut Microbiota in Mice Induced by Chronic Alcohol Intake

Honey-processed Astragalus (HPA) is a mixture of Astragalus and honey, which is a processed product of Chinese medicine. It has the active ingredients of Astragalus and the unique effects of honey. However, the mechanism of HPA for improving alcoholic liver disease (ALD) is not clear. The purpose of this study is to explore the ameliorating effect and mechanism of HPA (4 and 8 g/kg bw) on alcoholic liver injury. Two doses of HPA were orally administered to alcohol-treated mice for four weeks. The results showed that HPA could effectively reduce triglycerides (TG) by 59% and free fat acid (FFA) and total cholesterol (TC) in serum and hepatic were reduced by least 25.9%. HPA could cause a decrease in serum low-density lipoprotein cholesterol (LDL-C) from 0.145 mM to 0.117 mM, and the serum high-density lipoprotein cholesterol (HDL-C) was increased. After alcohol-treated mice were supplemented with HPA, antioxidant markers (superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and Glutathione peroxidase (GSH-Px)), liver function index (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)), proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)), and liver tissue were all significantly improved. This is related to the fact that HPA can promote the expression of oxidative stress-related genes and inhibit the expression of inflammation-related genes. In addition, HPA could also regulate the disturbance of the intestinal microflora. In general, HPA could significantly improve the accumulation of serum and liver lipids caused by alcohol and the imbalance of intestinal flora in mice. It could also improve liver function, oxidative stress, and inflammation.

A novel antagonist of TRPM2 and TRPV4 channels: Carvacrol.

The overload cytosolic free Ca2+ (cCa2+) influx-mediated excessive generation of oxidative stress in the pathophysiological conditions induces neuronal and cellular injury via the activation of cation channels. TRPM2 and TRPV4 channels are activated by oxidative stress, and their specific antagonists have not been discovered yet. The antioxidant and anti-Covid-19 properties of carvacrol (CARV) were recently reported. Hence, I suspected possible antagonist properties of CARV against oxidative stress (OS)/ADP-ribose (ADPR)-induced TRPM2 and GSK1016790A (GSK)-mediated TRPV4 activations in neuronal and kidney cells. I investigated the antagonist role of CARV on the activations of TRPM2 and TRPV4 in SH-SY5Y neuronal, BV-2 microglial, and HEK293 cells. The OS/ADPR and GSK in the cells caused to increase of TRPM2/TRPV4 current densities and overload cytosolic free Ca2+ (cCa2+) influx with an increase of mitochondrial membrane potential, cytosolic (cROS), and mitochondrial (mROS) ROS. The changes were not observed in the absence of TRPM2 and TRPV4 or the presence of Ca2+ free extracellular buffer and PARP-1 inhibitors (PJ34 and DPQ). When OS-induced TRPM2 and GSK-induced TRPV4 activations were inhibited by the treatment of CARV, the increase of cROS, mROS, lipid peroxidation, apoptosis, cell death, cCa2+ concentration, caspase -3, and caspase -9 levels were restored via upregulation of glutathione and glutathione peroxidase. In conclusion, the treatment of CARV modulated the TRPM2 and TRPV4-mediated overload Ca2+ influx and may provide an avenue for protecting TRPM2 and TRPV4-mediated neurodegenerative diseases associated with the increase of mROS and cCa2+.Graphical abstractThe possible TRPM2 and TRPV4 blocker action of carvacrol (CARV) via the modulation oxidative stress and apoptosis in the SH-SY5Y neuronal cells. TRPM2 is activated by DNA damage-induced (via PARP-1 activation) ADP-ribose (ADPR) and reactive oxygen species (ROS) (H2O2), although it is inhibited by nonspecific inhibitors (ACA and 2-APB). TRPV4 is activated by the treatments of GSK1016790A (GSK), although it is inhibited by a nonspecific inhibitor (ruthenium red, RuRe). The treatment of GSK induces excessive generation of ROS. The accumulation of free cytosolic Ca2+ (cCa2+) via the activations of TRPM2 and TRPV4 in the mitochondria causes the increase of mitochondrial membrane depolarization (ΔΨm). In turn, the increase of ΔΨm causes the excessive generation of ROS. The TRPM2 and TRPV4-induced the excessive generations of ROS result in the increase of apoptosis and cell death via the activations of caspase -3 (Casp-3) and caspase -9 (Casp-9) in the neuronal cells, although their oxidant actions decrease the glutathione (GSH) and glutathione peroxidase (GSHPx) levels. The oxidant and apoptotic adverse actions of TRPM2 and TRPV4 are modulated by the treatment of CARV Supplementary InformationThe online version contains supplementary material available at 10.1007/s11011-021-00887-1.

Gut-Liver Axis reveals the protective effect of exopolysaccharides isolated from Sporidiobolus pararoseus on alcohol-induced liver injury

• A study about Exopolysaccharides (EPS) from S. pararoseus against ALD. • The effects of EPS on ALD in oxidative stress, inflammation, and lipid accumulation. • The effects of EPS on ALD based on liver-gut axis. • The mechanism analysis of EPS to protect intestinal barrier function. Chronic and excessive alcohol consumption can lead to the development of alcoholic liver disease (ALD), which is characterized by oxidative damage, inflammation, and impaired intestinal barrier function. To evaluate the effect of exopolysaccharides (EPS) from Sporidiobolus pararoseus on ALD, alcohol was used in this study to cause liver damage in mice. Then, the antioxidant and anti-inflammation activities and protective effect of EPS on the intestinal barrier function were further explored in an ALD model. The results show that the histopathological change and liver injury were significantly improved in the EPS group. EPS treatment significantly increased the levels of superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) (P < 0.05), and weak reduced the elevation of malondialdehyde (MDA) induced by ALD. Several inflammatory markers, including tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β were reduced significantly after the intervention by EPS (P < 0.01). In addition, EPS also inhibited the injury of the small intestine and regulated the intestinal barrier function. A mechanism study shows that EPS restrained oxidative stress and protected intestinal barrier function by activating Nrf2/HO-1/PPAR-γ signaling pathway and upregulating the expression of ZO-1 and occludin, indicating that EPS showed protective activity against ALD through the gut-hepatic axis. Therefore, EPS has potential as a protective agent against ALD.

Assessment of gentamicin and cisplatin-induced kidney damage mediated via necrotic and apoptosis genes in albino rats

BackgroundGentamicin (GM) is a low-cost, low-resistance antibiotic commonly used to treat gram-negative bacterial diseases. Cisplatin (Csp) is a platinum-derived anti-neoplastic agent. This experiment aimed to identify the early signs of gentamicin and cisplatin-induced nephrotoxicity in rats. Thirty Wistar rats were divided into three groups of 10: a control group, which received no treatment; a gentamicin group administered by a dose of (100 mg/kg, IP) for 7 consecutive days, and a cisplatin group was administered intraperitoneal in a dose of (1.5 mg/kg body weight) repeated twice a week for 3 weeks.ResultsBoth experimental groups exhibited increased levels of creatinine, urea, and uric acid, with the cisplatin-treated group showing higher levels than the gentamicin group. Experimental groups also exhibited significantly increased Malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GSH-Px) with more pronounced effects in the cisplatin-treated group. Further, both experimental groups exhibited significant up-regulation of Tumor Necrosis Factor α (TNF-α), caspase-3, and Bax and down regulation of Bcl-2.ConclusionThese findings confirm the use of necrotic, apoptotic genes as early biomarkers in the detection of tubular kidney damage. Further, cisplatin was shown to have a greater nephrotoxic effect than gentamicin; therefore, its use should be constrained accordingly when co-administered with gentamicin.

S-ketamine alleviates carbon tetrachloride-induced hepatic injury and oxidative stress by targeting the Nrf2/HO-1 signaling pathway.

The aim of the present study was to investigate the protective effect of S-ketamine (S-KET) against carbon tetrachloride (CCl4) - induced liver damage and oxidative stress, as well as to elucidate the related underlying mechanisms. Blood was collected to measure biochemical parameters (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (TB) and γ-glutamyltransferase (γ-GT)) and the liver was harvested for histopathological analysis of enzymes related to the antioxidant response (malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX)). Liver cell apoptosis was evaluated using the TUNEL assay. In addition, the expression levels of apoptosis-related proteins and the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway were detected by Western blot analysis to explore potential mechanisms. S-KET protected the liver from CCl4-induced damage. The changes to the liver biochemical parameters (increased ALT, AST, ALP, TB, and γ-GT) and oxidative stress-related indicators (increased MDA; depleted SOD, GSH, and GSH-PX) induced by CCl4 were inhibited by S-KET. S-Ket also inhibited CCl4-induced cell apoptosis, the changes in expression of related proteins, and blocked CCl4-induced liver injury and oxidative stress via activation of the Nrf2/HO-1 signaling pathway. S-KET effectively protected the liver by inhibition of CCl4-induced damage via upregulation the Nrf2/HO-1 signaling pathway.

Hengshun Aromatic Vinegar Ameliorates Vascular Endothelial Injury via Regulating PKCζ-Mediated Oxidative Stress and Apoptosis.

Vascular endothelial injury (VEI) is an early event of atherosclerosis, and reversing endothelial dysfunction has become a new trend in the prevention and treatment of cardiovascular diseases. Hengshun aromatic vinegar (HSAV), a traditional vinegar, has been reported to have many pharmacological activities, but its effect against VEI and the molecular mechanism are still unknown. In this study, effects of HSAV on VEI were evaluated in H2O2-induced human umbilical vein endothelial cells (HUVECs) and methionine-induced VEI in rats. Results showed that HSAV significantly increased cell viability, inhibited apoptosis, and reduced the generation of reactive oxygen species (ROS) in H2O2-induced HUVECs. Meanwhile, HSAV decreased serum homocysteine (Hcy), endothelin 1 (ET-1), and oxidized low-density lipoprotein (ox-LDL) levels, increased nitric oxide (NO) and endothelin nitric oxide synthase (eNOS) levels, ameliorated pathological changes in rats with VEI induced by methionine. In parallel, HSAV relieved oxidative stress by decreasing malondialdehyde (MDA) level and increasing superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels in rats with VEI. Mechanism studies indicated that HSAV markedly downregulated the expression of protein kinase C zeta (PKCζ), and consequently regulated sirtuin 1 (Sirt1)-mediated oxidative stress signal pathway, and protein inhibitor of activated STATy (PIASy)-mediated apoptosis pathway, leading to the alleviation of oxidative stress and inhibition of apoptosis. These regulative effects of HSAV were further validated by knockdown and overexpression of PKCζ in vitro. In conclusion, HSAV showed protective effect against VEI by inhibiting PKCζ and, thereby, ameliorating oxidative stress and inhibiting apoptosis. This study not only provides guidance for the consumption of vinegar in daily life but also promotes the development of diet supplement for disease prevention.