Hepatic Malondialdehyde Levels Research Articles

Mechanisms of Ardisia japonica in the Treatment of Hepatic Injury in Rats Based on LC-MS Metabolomics.

The mechanism of action of Ardisia japonica in the treatment of immune liver injury was systematically analyzed from the perspective of the biological metabolic network by using non-targeted metabolomics combined with biological network analysis tools. A rat model of acute immune hepatic injury was established by Concanavalin A (Con A) and the efficacy of the treatment of acute immune liver injury was judged by gavage of A. japonica. Liquid chromatography-mass spectrometry (LC-MS)-based plasma metabolomics was used to identify the key metabolites and metabolic pathways for the hepatoprotective effects of A. japonica. The results demonstrated that A. japonica reduced the levels of inflammatory parameters, decreased hepatic malondialdehyde levels, and enhanced hepatic antioxidant enzyme activity in animal experiments. The clustering of metabolomic samples showed significant separation in principal component analysis plots and the three groups in PLS-DA and OPLS-DA models could be clearly distinguished in multivariate statistical analysis. Among the 937 total metabolites, 445 metabolites were significantly different between the control and model groups, while 144 metabolites were identified as metabolites with differences between the model and administration groups, and a total of 39 differential metabolites were identified to affect the metabolic levels of the three groups. The differential metabolites were principally involved in the citric acid cycle, glutathione metabolism, vitamin B6 metabolism, and steroid hormone biosynthesis. This study found that A. japonica can significantly inhibit acute liver injury in rats, and exert a hepatoprotective effect through anti-inflammatory effect, inhibition of lipid peroxidation, improvement of the antioxidant defense system, and regulation of metabolites and related metabolic pathways. This study will provide a theoretical basis for the application of A. japonica in the treatment of the liver injury.

Sesame oil ameliorates valproic acid-induced hepatotoxicity in mice: integrated in vivo–in silico study

Sesame oil (SO) has been exhibited to have anti-inflammatory and antioxidant influences. The goal of this experiment was to look into SO’s hepato-protective properties and underlying processes in valproic acid (VPA)-induced hepatotoxicity. Molecular docking was carried out to clarify the functional and structural underlying mechanism of SO ameliorative effect. Mice were given 8 mL/kg/day of SO (orally) and 100 mg/kg/day of VPA (i.p.) for 21 days. The results revealed that VPA caused a considerable increase in hepatic malondialdehyde levels while decreasing the activity of glutathione peroxidase (GPx) enzyme. There was also a significant rise in serum levels of interleukins 1β and 6 (IL-1β and IL-6) and a significant decrease in hepatic (PXR) gene expression level. SO co-administration with VPA significantly normalized the antioxidant and anti-inflammatory status and upregulated the gene expression level of PXR. In silico docking analysis results confirmed these results. This study concluded that supplementation of SO attenuated VPA-induced oxidative stress and inflammation. Hence, it was recommended as a dietary supplement for protection against VPA-induced hepatotoxicity. Communicated by Ramaswamy H. Sarma

Whole Eggs Improve High-Fat Diet-Induced Disorders of the Hepatic Lipid Profile and Gut Microbiota in Mice

The relationship between egg consumption and disturbances of hepatic lipid metabolism remains controversial. Recent studies indicate that egg consumption showed favorable effects on dyslipidemia, while underlying mechanisms remain largely undefined. In this study, the high-fat diet was fed to C57BL/6J mice to induce lipid metabolism disorders, aiming to disclose the effects of the whole eggs (WEs) and yolk-free egg substitute (YFES) on the hepatic lipid profile and gut microbiota. The daily WE/YFES dose for mice was 7.55 mg/g of mouse weight. The results showed that WE inhibited body weight gain and significantly decreased hepatic triglyceride (TG) by 49.6% while showing insignificant effects on the total cholesterol in the liver. Both WE and YFES alleviated hepatic oxidative stress by decreasing hepatic levels of malondialdehyde. Lipidomic analysis revealed that diacylglycerol, lysophosphatidylcholines, ceramide, and free fatty acids were the major lipid species upregulated by WE. Moreover, WE showed beneficial effects on gut microbiota by increasing the abundance of Bacteroidota while decreasing Proteobacteria levels. The correlation analysis showed that Lactobacillales and Bacteroides displayed a significant negative correlation with hepatic TG and free fatty acids (18:4), while positively correlated with phosphatidylethanolamine biomarkers. These results evidenced that WE was more effective than YFES in improving hepatic lipid profiles and regulating the gut microbiota, resulting in increased levels of probiotics and inhibited TG accumulation and oxidative stress through the gut–liver axis. Therefore, it could be concluded that the consumption of WE instead of YFES would be helpful in relieving hepatic dyslipidemia in the short term.

Ameliorative effects of monascin from red mold rice on alcoholic liver injury and intestinal microbiota dysbiosis in mice

Monascus-fermented red mold rice (RMR) has excellent physiological efficacy on lipid metabolism and liver function. This study investigated the ameliorative effects of monascin (MS) from RMR on alcoholic liver injury (ALI) in mice, and further illustrated its mechanism of action. Results indicated that dietary MS intervention obviously ameliorated lipid metabolism and liver function in mice with over-drinking. In addition, MS intervention alleviated alcohol-induced oxidative stress in the liver by reducing the hepatic activities of lactate dehydrogenase (LDH) and hepatic levels of malondialdehyde (MDA), increasing the hepatic activities of catalase (CAT), superoxide dismutase (SOD), alcohol dehydrogenase (ADH) and hepatic levels of glutathione (GSH). 16S rRNA amplicon sequencing showed that excessive drinking had a significant effect on the composition of the gut microbiota in mice. MS intervention was beneficial to ameliorate intestinal microbiota dysbiosis by elevating the proportion of Lactobacillus, Lachnospiraceae_UCG-006, Coriobacteriales, etc., but decreasing the proportion of Staphylococcus, Muribaculaceae, Desulfovibrionaceae, etc. Additionally, correlation analysis indicated that the key intestinal bacterial taxa intervened by MS were closely related to some biochemical indicators of lipid metabolism, liver function and oxidative stress. Moreover, liver metabolomics analysis revealed that dietary MS supplementation significantly regulated the levels of liver metabolites involved in taurine and hypotaurine metabolism, riboflavin metabolism, and purine metabolism, etc. Furthermore, MS intervention regulated gene transcription and protein expression associated with lipid metabolism and oxidative stress in the liver. In short, these findings suggest that MS mitigates alcohol-induced hepatic oxidative damage through modulating the intestinal microbiome and liver metabolic pathway, and thus can be served as a functional component to prevent alcoholic liver disease.

Lycopene ameliorates hyperlipidemia via potentiation of AMP-activated protein kinase and inhibition of ATP-citrate lyase in diabetic hyperlipidemic rat model

AimThe present study aimed mainly to demonstrate the metabolic effects of lycopene (LYC) or atorvastatin (ATOR) in diabetic hyperlipidemic rat model. Main methodsRats were randomly classified into four groups; the first was fed normal chow diet (NC) while the other three groups received streptozotocin (STZ) along with CCT-diet. The second group received no treatment (diabetic hyperlipidemic control, DHC), the third one received ATOR (50 mg/kg/day) while the fourth one received LYC (20 mg/kg/day). Serum and tissue samples were collected for biochemical and histological evaluations. Key findingsDHC rats demonstrated significant hyperglycemia, dyslipidemia, increased hepatic fatty acid synthetase (FAS), malondialdehyde (MDA), tumor necrosis factor- alpha (TNF-α), 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase and ATP citrate lyase (ACLY). However, hepatic reduced glutathione (GSH) and phosphorylated form of AMP-activated protein kinase (AMPK-P) activities showed significant decreases. ATOR or LYC administration induced hypoglycemic and hypolipidemic effects; decreased hepatic levels of MDA, TNF-α, HMG-CoA reductase, ACLY and FAS along with GSH and AMPK-P increases. Histopathological findings showed clear correlation with the biomarkers results. SignificanceLYC demonstrated favorable significant effects regarding the biomarkers studied as compared to ATOR and may be expressed as a potent therapeutic agent of natural origin for hyperlipidemia complications either alone or in combination with other hypolipidemic drugs.

Chitosan-Ocimum basilicum nanocomposite as a dietary additive in Oreochromis niloticus: Effects on immune-antioxidant response, head kidney gene expression, intestinal architecture, and growth

Several studies have looked into the use of basil, Ocimum basilicum (L.) in aquaculture as a dietary additive; however, more research is needed to see the possibility of it's including in nanocarriers in aquafeeds. An experiment was undertaken to highlight the efficacy chitosan-Ocimum basilicum nanocomposite (COBN), for the first time, on Nile tilapia (Oreochromis niloticus) growth, stress and antioxidant status, immune-related parameters, and gene expression. For 60 days, fish (average weight: 23.55 ± 0.08 g) were fed diets provided with different concentrations of COBN (g/kg): 0 g [COBN0], 1 g [COBN1], 2 g [COBN2], and 3 g [COBN3], where COBN0 was kept as control diet. Following the trial, the fish were challenged with pathogenic bacteria (Aeromonas sobria) and yeast (Candida albicans) infection. In comparison to the control (COBN0), a notable increase in growth parameters (weight gain, feed intake, and specific growth rate) and intestinal morphometric indices (average intestinal goblet cells count, villous width, and length) in all COBN groups was observed, where COBN2 and COBN3 groups had the highest values. The COBN diets significantly (p < 0.05) declined levels of serum triglycerides, glucose, cholesterol, and hepatic malondialdehyde. Moreover, the higher levels of serum biochemical biomarkers (growth hormone, total protein, globulin, and albumin), immunological parameters (phagocytic activity%, nitric oxide, and lysozyme), and hepatic antioxidant parameters (superoxide dismutase, total antioxidant capacity, and glutathione peroxidase) were obvious in the COBN2 and COBN3 groups followed by COBN1. The immune-antioxidant genes (TNF-α, IL-10, IL-1β, TGF-β, GPx, and SOD) were found to be considerably up-regulated in all COBN groups (COBN2 and COBN3 followed by COBN1). Fifteen days post-challenge with A. sobria and C. albicans, the highest survival rate was recorded in the COBN2 group (83.33 and 91.67%) followed by the COBN3 group (75 and 83.33%), respectively. The findings showed that a dietary intervention with COBN can promote growth, intestinal architecture, immunity, and antioxidant markers as well as protect O. niloticus against A. sobria and C. albicans infection. As a result, the COBN at a dose of 2 g/kg could be used as a food additive for the sustainable aquaculture industry.

Heat stress in broilers of liver injury effects of heat stress on oxidative stress and autophagy in liver of broilers

This study aimed to investigate the effect of chronic heat stress on oxidative stress in liver of broilers. In our study, chickens were randomly allocated to control 1 group (control 7 d), heat stress 1 group (HS1, 7 d), control 2 group (control 14 d) and heat stress 2 group (HS2, 14 d), with 30 replicates in each group. Broilers in heat stress groups exposed 8 h/day heat stress (35 ± 2°C) for 7 or 14 consecutive days, and the rest of time per day were kept at 23 ± 2℃ the same as control group broilers. Growth performance and the liver tissues were collected for histological observation and detection of organ index and liver redox status. The serum indicators (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) related to liver injury were determined. Moreover, Nrf2-related genes and protein expression levels in liver were measured. The results showed that in heat stress group broilers the body weight gain, feed conversion ratio, liver weight, and liver index were decreased, inflammatory cells infiltration in liver, and serum AST level was enhanced, compared with control group broilers. Moreover, the hepatic malondialdehyde (MDA) and superoxide dismutase (SOD) level were increased after 1 wk of heat stress. Nrf2, Sqstm1/p62, HO-1, and NQO1 mRNA expressions in the liver of broilers were decreased by heat stress. P62 and p-p62 protein expressions were significantly up-regulated, but Nrf2 and keap1 protein level was decreased in heat stress group broilers as compared to control group. The mRNA expression levels of Beclin1, LC3-I, LC3-II were down-regulated significantly with heat stress for 1 wk. The mRNA expression level of mTOR up-regulated after 2 wk of heat stress. In conclusion, heat stress induced liver injury of broilers by down-regulating Nrf2-keap1 signaling pathway and autophagy.

Antioxidant Mechanism of Renal and Hepatic Failure Prevention Related to Paracetamol Overdose by the Aqueous Extract of Amblygonocarpus andongensis Stem Bark.

Paracetamol is a commonly used analgesic/antipyretic whose long-term intake or overdose is associated with renal and hepatic injuries. The aim of this study was to determine the hepatonephroprotective mechanisms of the aqueous extract of Amblygonocarpus andongensis stem bark (AEAASB) on renal and hepatic failure resulting from paracetamol overdose. Forty-five rats were divided into nine groups (n = 5); these were treated once daily for 8 days with 5 ml/kg distilled water (normal, negative, and satellite controls); 0.9% normal saline and 140 mg/kg N-acetyl-cysteine (positive controls); 125, 250, and 500 mg/kg AEAASB (test groups); and 500 mg/kg AEAASB (satellite test). On day 8 after different treatments, hepatonephrotoxicity was induced in all the groups except the normal group by oral administration of a single dose of paracetamol (1000 mg/kg). Urinary, hematological, serum, and oxidative stress parameters and in vitro antioxidant activity of AEAASB were evaluated. Histological sections of the liver and kidney were performed. AEAASB significantly decreased urea, creatinine, transaminases, alkaline phosphatase, and bilirubin (p < 0.001) at 500 mg/kg compared to the negative control. Significant decreases in hepatic (p < 0.01) and renal (p < 0.001) malondialdehyde levels were associated with increases in superoxide dismutase, catalase, and reduced glutathione levels in 500 mg/kg AEAASB compared with the negative control. Histological analysis showed that AEAASB prevented paracetamol-induced renal and liver tissue damage. Furthermore, AEAASB revealed a very strong antioxidant activity (inhibitory concentration 50 = 180 μg/ml, antioxidant activity index = 5.55) with an ability to scavenge 63.03% 2,2-diphenyl-2-picrylhy-drazyl radical and reduced ferric iron by 52.68 mgEqVitC/100 g DM. The hepatonephroprotective effect of AEAASB might result from its ability to improve the antioxidant status through the stimulation of antioxidant factors and the scavenging of free radicals. This property could be ascribed to the presence of some classes of bioactive compounds such as phenolic compounds in great amounts.

Probiotics and their beneficial effects on alcohol-induced liver injury in a rat model: the role of fecal microbiota

BackgroundCurrent therapies for alcohol-induced liver injury are of limited efficacy and associated with significant side effects. With the proposed pathophysiology of alcohol-induced liver injury to be related to deranged gut microbiota, we hypothesized that probiotics would have beneficial effects in attenuating alcohol-induced liver injury.MethodsTwenty-four male Sprague-Dawley rats were divided into 4 groups: control group, alcohol group, Lactobacillus plantarum group, and mixed-strain probiotics group. After 4 weeks, all rats were sacrificed, and blood samples were analyzed for ALT, lipopolysaccharide level (LPS), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Liver tissues were processed for histopathology, malondialdehyde (MDA) level and immunohistochemistry for toll-like receptors 4 (TLR-4). Stool samples were collected, and 16S rRNA sequencing was used to analyze the fecal microbiota.ResultsLiver histopathology showed the presence of significant hepatocyte ballooning in the alcohol group as compared with the control group, and the treatment with L. plantarum or mixed-strain probiotics alleviated these changes. Significant elevation of serum ALT, LPS, IL-6, and TNF-α, hepatic MDA levels, and hepatic TLR-4 expression were observed in alcohol-fed rats as compared with control rats. The administration of L. plantarum or mixed-strain probiotics restored these changes to the levels of control rats. The relative abundance of fecal bacteria at genus level showed a significant reduction in Allobaculum, Romboutsia, Bifidobacterium, and Akkermansia in the alcohol group as compared with the control group. In probiotics-treated rats, significant increases in Allobaculum and Bifidobacterium were observed, while the relative abundance of Romboutsia and Akkermansia was unchanged compared to the alcohol group. A reduction in alpha diversity was observed in alcohol-treated rats, whereas the improvement was noted after probiotic treatment.ConclusionsThe treatment with Lactobacillus, whether as single-, or mixed-strain probiotics, was beneficial in reducing the severity of alcohol-induced liver injury likely through the increase in beneficial bacteria, and the reduction of inflammatory responses, and oxidative stress.

Orientin Attenuated d-GalN/LPS-Induced Liver Injury through the Inhibition of Oxidative Stress via Nrf2/Keap1 Pathway.

Oxidative stress is involved in the pathogenesis of liver diseases, including liver injury, a serious health problem worldwide. Natural polyphenols have attracted increasing attention as potential agents for the prevention and treatment of liver diseases. Orientin, a flavonoid component with antioxidant capacity, has been regarded as a promising nutraceutical for patients with liver damage. This study aimed to investigate the amelioration effect of orientin on d-galactosamine and lipopolysaccharides (d-GalN/LPS) induced liver injury in mice, with a focus on its underlying mechanisms by using the H2O2-induced oxidative damage model of HepG2 cells. Results indicated that orientin alleviated d-GalN/LPS-induced liver damage by improving the hepatic histological changes and reducing the levels of hepatic and serum alanine aminotransferase and aspartic acid aminotransferase. Additionally, supplementation of orientin improved the antioxidant ability in mice by decreasing the levels of hepatic malondialdehyde, protein carbonyl, myeloperoxidase, nitric oxide, glutathione, glutathione peroxidase, gluathione reductase, and superoxide dismutase. Orientin treatment significantly elevated both the protein and mRNA expressions of nuclear factor erythroid 2-related factor 2, Kelch-like ECH-associated protein-1, heme oxygenase-1, and nicotinamide quinone oxidoreductase 1 in liver and HepG2 cells. The management of orientin also elevated the protein expression of glutathione S-transferase and Maf in HepG2 cells. Taken together, it suggested that orientin played an amelioration effect on liver injury by suppressing oxidative stress, which might be strongly related to the activation of Nrf2/ARE through PI3K/Akt and P38/MAPK signal pathways.

Protective Effects of Glochidion wallichianum Mull. Arg. on Ethanol-induced Liver Injury in Rats

Chronic ethanol consumption leads to the development of liver disease. In the present study, the effects of Glochidion wallichianum Mull. Arg. ethanol extract (GWE) on chronic ethanol-induced liver injury in rats were evaluated. Total phenolic and flavonoid contents and in vitro antioxidant activities were determined. In the in vivo experiment, male Wistar rats were divided into 5 groups: Control, ethanol, ethanol plus low and high doses of GWE (ethanol+GWE300 and ethanol+GWE600, respectively) and GWE alone (GWE600). All treatments were administered orally for 28 days. Serum biochemical profiles, hepatic malondialdehyde (MDA) levels, antioxidant enzyme activities, cytochrome P450 2E1 (CYP2E1) expression, and liver histopathology were assessed. GWE contained high concentrations of total phenols and total flavonoids and exhibited inhibition of 2,2-diphenyl-1-picrylhydrazyl free radical. The GWE treatment significantly decreased alanine aminotransferase (ALT) levels, reduced hepatic MDA levels, increased catalase (CAT) activity, and improved histopathological alterations. However, compared with the control condition, GWE alone induced a low level of necrosis. The expression of the CYP2E1 mRNA was not different among the groups (p &gt; 0.05). Based on these findings, GWE exerts a protective effect on ethanol-induced liver injury in rats through its antioxidant activity.&#x0D; HIGHLIGHTS&#x0D; &#x0D; Chronic alcohol abuse causes liver injury which leads to alcohol liver disease&#x0D; Administration of Glochidion wallichianum Mull. Arg. ethanol extract declined oxidative stress marker in hepatic tissue, improved hepatic antioxidant enzyme on chronic ethanol-induced liver injury in rats&#x0D; Glochidion wallichianum Mull. Arg. possibly serves as supplement to attenuate ethanol-induced liver injury&#x0D; &#x0D; GRAPHICAL ABSTRACT

Ablation of Carotenoid Cleavage Enzymes BCO1 & BCO2 Alters Gut Microbial and Plasma Metabolomic Profiles in High Refined Carbohydrate Diet-Fed Mice

Objectivesβ-Carotene-15,15′-oxygenase (BCO1) and β-carotene-9′,10′-oxygenase (BCO2) cleave carotenoids to form vitamin A or apo-carotenoid species. Beyond these roles, BCO1 and BCO2 have been implicated in modulating lipid, cholesterol, and oxidative stress-related processes, yet less is known about their combined influence on shaping gut microbial and plasma metabolic profiles. Current intake of refined carbohydrates and added sugars exceeds the recommendations within the Dietary Guidelines for Americans, which may contribute to the development of nonalcoholic fatty liver disease (NAFLD). In the present study, we aimed to uncover whether mice with systemic ablation of BCO1-/-/BCO2-/- (DKO) display distinctive phenotypes in response to a high refined carbohydrate diet (HRCD) model of NAFLD. MethodsMale, six-week-old C57BL/6J wild type mice (WT) and DKO mice were fed a chow diet or a HRCD (66.5% carbs including sucrose) for 24 weeks. We used fecal and plasma samples to respectively perform 16S rDNA sequencing, and both targeted and untargeted metabolomics using our UHPLC-QTOF-MS platform, a targeted Biocrates MxP Quant 500 kit, and a complimentary untargeted analysis of phospholipids from the METLIN database. Data were analyzed using QIIME2-DEseq2, MetaboAnalyst 5.0, MassHunter Qualitative Analysis, and MicrobiomeAnalyst. ResultsHRCD-fed WT and DKO mice developed similar levels of hepatic steatosis although DKO mice had significantly higher hepatic levels of malondialdehyde (MDA). Interestingly, in both chow-fed and HRCD-fed DKO mice, plasma adiponectin and hepatic bile acids were significantly lower compared to respective WT groups. Our metabolomics data revealed that DKO mice displayed significant alterations in ceramide, cholesterol ester, triglyceride, and phospholipid classes under both chow and HRCD conditions. Additionally, when compared to HRCD-fed WT mice, HRCD-fed DKO mice displayed significantly reduced alpha diversity and possessed significant compositional differences based on Bray Curtis dissimilarity measures. ConclusionsBCO1/BCO2 DKO mice display altered metabolomic and gut microbial profiles. Carotenoid cleavage enzymes affect diverse physiological processes, which involve lipid metabolism and the gut microbiome. Funding SourcesUSDA/ARS and NIFA/AFRI.

Diets Partially Replaced With Cassava Residue Modulate Antioxidant Capacity, Lipid Metabolism, and Gut Barrier Function of Huanjiang Mini-Pigs.

Agricultural by-products have been identified as potential feed resources in animal production. The present study investigated the effects of cassava residue (CR) or fermented CR (FCR) on antioxidant capacity, immunity, gut barrier functions, and lipid metabolism in pigs. A total of 120 healthy Huanjiang mini-piglets were assigned into three groups, including control group (basal diet), CR group (basal diet + 5% CR), and FCR group (basal diet + 5% FCR). The experiment lasted for 30 days. The results showed that, dietary CR or FCR supplementation increased the jejunal catalase (CAT, P = 0.063) and glutathione peroxidase (GSH-Px, P < 0.05) levels and hepatic superoxide dismutase (SOD, P < 0.05) level while decreased (P = 0.077) ileal malondialdehyde (MDA) level, when compared with the control group. Dietary CR supplementation increased intestinal SOD and hepatic GSH-Px levels, whereas decreased jejunal and hepatic MDA levels (P < 0.05). Dietary CR supplementation increased the levels of secretory immunoglobulin A (sIgA) in the intestine and liver, as well as jejunal interleukin (IL)-10, ileal tumor necrosis factor (TNF)-α, and hepatic interferon (IFN)-γ, whereas dietary CR or FCR supplementation decreased the jejunal IL-1β level and increased hepatic IL-10 level (P < 0.05). In the intestinal microbiota analysis, dietary CR or FCR supplementation enhanced the colonic α-diversity and ileal Actinobacteria abundance, whereas decreased ileal Verrucomicrobia and colonic Tenericutes abundances (P < 0.05). In addition, dietary FCR supplementation increased Firmicutes and decreased Bacteroidetes abundances in the ileum and colon, whereas CR supplementation increased Escherichia-Shigella and decreased Terisporobacter abundances in the ileum (P < 0.05). Moreover, dietary CR or FCR supplementation up-regulated (P < 0.05) the gene expressions related to gut barrier functions of piglets. However, dietary CR supplementation showed negative impacts on hepatic lipid metabolism by up-regulating the expression of genes associated with fatty acid synthesis and triglyceride and lipid metabolism. In conclusion, dietary CR or FCR supplementation can maintain the health of piglets by increasing antioxidant capacity, gut barrier function, and altering the intestinal microbiota composition, but CR supplementation may increase the potential risk of abnormal lipid metabolism.

Evaluation of Hypoglycemic and Antioxidant Activities of Soybean Meal Products Fermented by Lactobacillus plantarum FPS 2520 and Bacillus subtilis N1 in Rats Fed with High-Fat Diet.

The hypoglycemic and antioxidant activities of Lactobacillus plantarum FPS 2520 and/or Bacillus subtilis N1 fermented soybean meal (SBM) in rats fed a high-fat diet (HFD) were investigated by assessing plasma glucose levels, insulin resistance, and oxidative stress-induced organ damage. Supplementation with FPS 2520- and/or N1-fermented SBM (500 and 1000 mg/kg of body weight per day) to HFD-induced obese rats for 6 weeks significantly down-regulated the concentration of plasma glucose during the oral glucose tolerance test (OGTT), as well as the concentration of fasting plasma glucose, insulin, and the value of the homeostasis model assessment of insulin resistance (HOMA-IR). In addition, plasma and hepatic levels of malondialdehyde (MDA) were alleviated in rats fed fermented SBM, especially SBM fermented by mixed strains. Moreover, fermented SBM treatment reduced HFD-exacerbated increases in plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and uric acid levels. Based on these results, we clearly demonstrate the effect of fermented SBM on improving insulin resistance and oxidation-induced organ damage. Therefore, it is suggested that fermented SBM has the potential to be developed as functional foods for the management of obesity-induced hyperglycemia and organ damage.

N,N-dimethylformamide-induced acute liver damage is driven by the activation of NLRP3 inflammasome in liver macrophages of mice

N,N-dimethylformamide (DMF) is a non-negligible volatile hazardous material in indoor and outdoor environments. Although the hepatotoxicity of DMF has been well recognized, the underlying mechanisms remain unclear and prophylactic medicine is still lacking. Herein, we established a DMF-induced acute liver injury mouse model and investigated the underlying mechanisms focusing on oxidative stress and the nucleotide-binding domain and leucine-rich repeat receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3) inflammasome. DMF was found to induce oxidative stress, evidenced by the elevation of hepatic malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) adducts levels, and the decline of reduced glutathione (GSH) levels. However, neither N-acetyl cysteine (NAC) nor sulforaphane (SF) ameliorated the hepatoxicity induced by DMF in mice. Interestingly, DMF exposure led to focal necrosis of hepatocytes and NLRP3 inflammasome activation before the onset of obvious liver damage. In addition, DMF exposure induced infiltration and proinflammatory/M1 polarization of macrophages in mice livers. Furthermore, the inactivation of hepatic macrophages by GdCl3 significantly suppressed DMF-induced elevation of serum aminotransferase activities, neutrophile infiltration, and activation of NLRP3 inflammasome in mice liver. Collectively, these results suggest that DMF-induced acute hepatotoxicity may be attributed to the activation of NLRP3 inflammasome in liver macrophages, but not oxidative stress.

The healing effects of Ganoderma lucidum on intestinal ischemia-reperfusion damage in rats

Background/Aim: Intestinal ischemia-reperfusion (I/R) injury causes serious clinical problems and carries high morbidity and mortality risks. Ganoderma lucidum (GL) is known as an anti-inflammatory immunomodulator and antioxidant. This study aimed to investigate the curative effects of GL on intestinal I/R injury in rats. Methods: Twenty-four Wistar-Albino male rats were randomly divided into three groups. After 30/90 minutes of I/R, intestinal and hepatic tissue examples were histologically examined. Biochemical analysis, serum, intestinal and hepatic tissue malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels were measured. Results: The I/R group had significantly elevated leukocyte, thrombocyte, serum, and intestinal and hepatic tissue MDA levels compared to the sham group (P < 0.05). Serum, intestinal tissue, and liver tissue SOD levels were significantly lower in the I/R group than in the control group (P < 0.05). In addition, GSH-Px levels measured in serum and liver tissue were lower in the I/R group. However, the use of GL prevented these decreases due to I/R damage. Prior administration of GL considerably alleviated histopathologic changes due to I/R injury in the intestinal and liver tissue samples. Conclusions: Our experimental study showed that I/R injury led to significant oxidative stress by inducing free oxygen radicals in intestinal and hepatic tissues. Serum and tissue MDA, SOD, and GSH-Px levels were considerably useful laboratory parameters in identifying oxidative stress. The protective effects of GL on intestinal I/R injury were promising considering these parameters.

Inhibition of HMGB1/TLR4 Signaling Pathway by Digitoflavone: A Potential Therapeutic Role in Alcohol-Associated Liver Disease.

Digitoflavone (DG) is a natural flavonoid abundant in many fruits, vegetables, and medicinal plants. We investigated whether DG inhibits lipid accumulation and inflammatory responses in alcoholic liver disease (ALD) in vivo and in vitro. The mouse ALD model was established by chronically feeding male C57BL/6 mice an ethanol-containing Lieber-DeCarli liquid diet. In vitro, mouse peritoneal macrophages (MPMs) and mouse bone marrow-derived macrophages (BMDMs) were stimulated with LPS/ATP, whereas HepG2 cells and mouse primary hepatocytes were treated with ethanol. DG reduced the serum levels of transaminase and serum and hepatic levels of triglycerides and malondialdehyde in ALD mice. DG downregulated SREBP1 and its target genes and upregulated PPARα and its target genes in the liver of mice with ALD. DG inhibited TLR4-mediated NLRP3 inflammasome activation, consequently reversing the inflammatory response, including the production of HMGB1, IL-1β, and IL-36γ, as well as the infiltration of macrophages and neutrophils. DG blocked NLRP3/ASC/caspase-1 inflammasome activation and HMGB1 release in LPS/ATP-stimulated MPMs. When Tlr4 was knocked in LPS/ATP-stimulated BMDMs, HMGB1 production and release were blocked, and NLRP3-mediated cleavage and release of IL-1β was suppressed in Hmgb1-silenced BMDMs. DG amplified these inhibitory effects in Tlr4 or Hmgb1 knockdown BMDMs. In ethanol-exposed hepatocytes, DG reduced lipogenesis and promoted lipid oxidation by inhibiting the HMGB1-TLR4 signaling pathway while suppressing the inflammatory response induced by ethanol exposure. Our data demonstrated that DG inhibited the occurrence of lipid accumulation and the inflammatory response via the HMGB1-TLR4 axis, underscoring a promising approach and utility of DG for the treatment of ALD.

Evaluation of the in vitro and in vivo antioxidant potential of Punica granatum L. against toluene-induced liver injuries in rats.

Background and Aim:Humans are more frequently exposed to chemicals in daily life by inhalation of indoor and outdoor air. However, abusers and workers are the most exposed to those chemicals and their health risks particularly, liver diseases. The present study investigated the protective effects of pomegranate juice (PJ) (Punica granatum) and pomegranate peel aqueous extract (PAE) supplementation against toluene (Tol)-induced hepatotoxicity in Wistar rats.Materials and Methods:A phytochemical analysis and assessment of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity were performed for the PJ and the PAE. The in vivo study was carried out using 70 Wistar rats that were divided into seven groups, each consisting of 10 rats. All groups were treated orally for 6 weeks as follows: Control (C), positive controls (CO: 1.25 mL/kg body weight [BW]; PJ: 4 mL/kg BW; and PAE: 400 mg/kg BW), Tol (550 mg/kg BW), and a mixture each of PJ-Tol and PAE-Tol. At the end of the 45th day of study, the hepatic biochemical markers (transaminases, alkaline phosphatase, total bilirubin, albumin, and total proteins) were auto-analyzed, as well as histology and oxidative stress markers of the liver were evaluated.Results:The phytochemical analysis revealed that the DPPH scavenging activity and the total phenolic, flavonoid, and tannin contents were higher in the pomegranate peel extract versus the juice. The results also showed that Tol significantly increased liver enzyme activities and total bilirubin levels, whereas albumin and total proteins were significantly decreased. Similarly, Tol provoked a significant increase in hepatic malondialdehyde levels, with a decrease in glutathione content and glutathione peroxidase activity. The biochemical changes agreed with the hepatic histological alterations. A significant improvement in all parameters was observed in the PAE-Tol group compared with the PJ-Tol group.Conclusion:Exposure to Tol altered the hepatic antioxidant and biochemical parameters and histological profile of the rats, and PAE was more powerful than PJ in reducing Tol liver injuries through its antioxidant activity.

Chemopreventive and hepatoprotective effects of genistein via inhibition of oxidative stress and the versican/PDGF/PKC signaling pathway in experimentally induced hepatocellular carcinoma in rats by thioacetamide

ABSTRACT Objective: Genistein is a recognized isoflavone present in soybeans with antioxidant, anti-inflammatory, antiangiogenic and antitumor activities. This study aimed to test ability of genistein in modulating versican/platelet derived growth factor (PDGF) axis in HCC. Methods: HCC was experimentally induced in male Sprague-Dawley rats then treated with 25 or 75 mg/kg genistein. Antioxidant activities of genistein was assessed by measuring the gene expression of Nrf2 and the hepatic levels of malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione. Expression of versican, PDGF, protein kinase C (PKC) and ERK-1 protein was assessed by Western blotting and immunostaining. Results: HCC induced an elevation in oxidative stress, PDGF, versican, PKC and ERK protein expression levels. Genistein significantly reduced an HCC-induced increase in oxidative stress. Moreover, genistein dose-dependently reduced HCC-induced elevation of PDGF, versican, PKC and ERK protein expression levels. Moreover, genistein helped retain a normal hepatocyte structure and reduced fibrous tissue deposition, especially in high dose. Conclusions: Genistein exerted antitumor and antioxidant effects and therefore suppress HCC development via inhibition of the PDGF/versican bidirectional axis, suppressing both ERK1 and PKC as downstream regulators. Therefore, genistein is a potential novel therapeutic candidate for improving the outcome of patients with HCC. Highlights Genistein is an isoflavones present in various soybeans and soy products. Genistein produced antitumor activity not only due to its antioxidant activity. Genistein expression of versican, PDGF, PKC and ERK. Genistein produced hepatoprotective effects.

Dihydromyricetin alleviates Escherichia coli lipopolysaccharide-induced hepatic injury in chickens by inhibiting the NLRP3 inflammasome

Dihydromyricetin (DHM), a flavonoid in vine tea, has many pharmacological activities, including anti-inflammatory and antibacterial effects. Lipopolysaccharide is the key inducer of inflammation in avian pathogenic Escherichia coli (E. coli) infection; however, the effect of DHM on E. coli lipopolysaccharide-induced hepatic injury remains unknown. The present study aimed to explore the role of the NLRP3 inflammasome in hepatic injury and the possible protective mechanisms of DHM against hepatic injury in chickens. The results showed that when chickens were administered lipopolysaccharide, liver damage was observed, accompanied by increased levels of serum transaminases and direct bilirubin. Additionally, hepatic expression levels of NLRP3 and caspase-1 p20, the subunit of caspase-1 that is cleaved after NLRP3 activation, significantly increased in liver injury. We found that treatment with MCC950, a specific NLRP3 inhibitor, significantly decreased serum transaminase activities, direct bilirubin content, and hepatic NLRP3 and caspase-1 p20 expression levels. DHM significantly reduced serum transaminase activities and direct bilirubin content and ameliorated histopathological and ultrastructural changes in the liver. DHM decreased hepatic levels of H2O2 and malondialdehyde and increased the activities of superoxide dismutase and glutathione peroxidase. Furthermore, DHM significantly decreased the expression levels of NLRP3, pro-caspase-1 and caspase-1 p20. Moreover, DHM reduced serum lactate dehydrogenase, IL-1β and IL-18 levels and repressed hepatic IL-1β, IL-18 and gasdermin A expression. The results demonstrated that the NLRP3 inflammasome was involved in the mechanism of lipopolysaccharide-induced hepatic injury. Furthermore, DHM could inhibit NLRP3 inflammasome activation and subsequent pyroptosis, eventually ameliorating E. coli lipopolysaccharide-induced liver injury.