Liver MDA Research Articles

Effect of energy levels on liver oxidative state and gut microbiota of laying hens fed a low-protein diet

IntroductionThe aim of this study was to investigate effect of energy levels on liver oxidative state and gut microbiota of laying hens fed a low-protein diet.MethodsA total of 216 laying hens (57-week-old with similar body weight) were randomly divided into 3 groups: low-energy and low-protein diet (LL: 10.73 MJ/kg), middle-energy and low-protein diet (ML: 11.15 MJ/kg), and high-energy and low-protein diet (HL: 11.57 MJ/kg) groups. The experiment lasted for 10 weeks.ResultsResults showed that the liver MDA level was higher, while the liver T-AOC level was lower in the HL group compared with LL and ML groups. The dominant phyla in LL group, ML group, and HL group were Bacteroidetes (38.08%, 39.69%, and 40.93%) and Firmicutes (16.78%, 18.37%, and 17.44%). At the genus level, Alistipes (9.45%) was abundant in the LL group. Bacteroides (14.46%), Phocaeicola (4.48%) and Precotella (2.95%) were highest in the ML group. Parabacteroides (1.78%) and Desulfovibrio (1.02%) were highest in the HL group. At the species level, Bacteroides fragilis (0.42%) is lowest in LL group, Desulfovibrio piger increased with the increase of energy. MDA was significantly and positively correlated with Methanobrevibacter woesei between ML group and HL groups (p < 0.05). T-AOC was highly significantly and positively correlated with Phocaeicola sp. Sa1YUN3 (p < 0.01) .DiscussionThis study found that high-energy and low-protein diets might cause liver oxidative stress by gut microbes in the laying hens.

Vitamin U alleviates AFB1-induced hepatotoxicity in pregnant and lactating mice by regulating the Nrf2/Hmox1 pathway

This study investigated the protective effect of Vitamin U on liver injury induced by aflatoxin B1 (AFB1) in maternal mice. 25 pregnant ICR mice were randomly divided into five groups: the AFB1 group (AF, 0.3 mg AFB1/kg b.w.), the Vitamin U group (U, 50 mg Vitamin U/kg b.w.), the AFB1 + Vitamin U group (AU, 50 mg Vitamin U /kg b.w. + 0.3 mg AFB1/kg b.w.), the control group (DMSO), and the MOCK group (distilled water). They were administered substances by gavage every day for 28 days. Results indicated that exposure to AFB1 increased the liver index and caused histological disruptions. Elevated serum levels of ALT and ALP were observed, along with a significant increase in liver MDA content and a decrease in GSH-Px and T-SOD levels. Moreover, the Keap1 and Hmox1 gene was downregulated with statistical significance, while the IL1β and TNFα gene were significantly upregulated. Vitamin U was demonstrated by the organized structure of liver cells in tissue slices, effectively reducing liver cell necrosis. This intervention was associated with a significant decrease in serum ALT and ALP activities, as well as a significant decrease in liver MDA content. Additionally, there were significant increases in liver T-SOD and GSH-Px levels, along with upregulation of mRNA and protein expression of Nfr2, Hmox1 and Keap1, and downregulation of mRNA expression of the IL1β gene. In summary, Vitamin U mitigated oxidative stress-induced liver injury by modulating the Nrf2/Hmox1 signaling pathway and inflammatory factors affected by AFB1.

Extraction and characterization of hepatoprotective polysaccharides from Anoectochilus roxburghii against CCl4-induced liver injury via regulating lipid metabolism and the gut microbiota

Anoectochilus roxburghii polysaccharides exhibit notable hepatoprotective effects, but the underlying substance basis and mechanisms remain unknown. In this study, four new polysaccharides named ARP-1a, ARP-1b, ARP-2a and ARP-2b, were isolated from A. roxburghii. Their structural characteristics were systematically analyzed using HPGPC, HPLC, GC–MS, IR and NMR analysis. ARP-1a, the leading polysaccharide isolated from A. roxburghii, was further evaluated for its hepatoprotective effects on acute liver injury mice induced by CCl4. ARP-1a significantly reduced the serum ALT, AST, TNF-α, IL-1β and IL-6 levels, liver MDA content, and increased the SOD and CAT activities and GSH level in liver. H&E staining revealed that ARP-1a pretreatment could markedly relieve liver injury. Further mechanism exploration indicated that ARP-1a could relieve CCl4-induced oxidative damage through activating the Nrf2 signaling. In addition, metabolomics, lipidomics and 16S rRNA amplicon sequencing were used to elucidate the underlying mechanisms of ARP-1a. Multi-omics analysis indicated that ARP-1a exerted hepatoprotective effect against CCl4-induced acute liver injury by regulating lipid metabolism and modulating the gut microbiota. In conclusion, the above results suggest that ARP-1a can be considered a promising and safe candidate for hepatoprotective drug, as well as a potential prebiotic for maintaining intestinal homeostasis and promoting human intestinal health.

Dietary curcumin supplementation attenuates hepatic damage and function abnormality in a chronic corticosterone-induced stress model in broilers

Chronic stress refers to the activation of the hypothalamic-pituitary-adrenal (HPA) axis and elevated blood contents of ACTH and corticosterone (CORT), exhibiting significant adverse effects on health outcomes. Currently, natural polyphenol compounds are increasingly being explored as potential therapeutic agents and have been considered as a treatment option for a variety of stress-induced diseases. Curcumin (CUR) is the main substance in Curcuma longa (Zingiberacea) rhizome that has strong health-beneficial properties. The study aimed to assess the potential protective effects of CUR on hepatic oxidative stress damage and abnormal lipid deposition in a chronic CORT-induced stress (CCIS) model in broilers. One hundred and twenty experimental broilers were randomly divided into 1) control group (CON), 2) CUR group (200 mg/kg feed), 3) CORT group (4 mg/kg BW CORT) and 4) CORT+CUR group (200 mg/kg feed plus 4 mg/kg BW CORT). The liver histology, glycolipid metabolism and oxidative stress were determined. In addition, qPCR was performed to identify shifts in genes expression. Compared with CON group, broilers under CCIS showed a decreased body weight, body weight gain and average daily gain, while dietary CUR significantly reversed these adverse effects. Furthermore, the plasma contents of TCH, TG, HDL-C, LDL-C, TP, GLB and AST were all significantly increased in CCIS broilers, while dietary CUR obviously alleviated the increase of TCH, HDL-C, LDL-C and AST, and relieved the hepatic lipid deposition disorder and liver injury. Moreover, CCIS significantly increased the contents of MDA in both liver and plasma, and decreased the content of plasma SOD, while CUR obviously reversed these changes, showing reduced oxidative stress damage. Finally, the mRNA expressions of FAS, ACC, SCD and the protein level of PPAR-γ were significantly increased, meanwhile the mRNA expression of lipolytic genes ACOX1, ATGL and CPT as well as two major intracellular antioxidant enzymes SOD1 and GPX1 were obviously decreased, while CUR effectively reversed these effects. These results showed that dietary CUR effectively alleviated CCIS-induced body weight loss, hepatic oxidative damage and lipid deposition disorder, suggesting the possible therapeutic effectiveness of CUR against hepatic damage and function abnormality caused by CCIS.

D-glucaro-1,4-lactone improves Diethylnitrosamine induced hepatocellular carcinoma in rats via the uric acid-ROS pathway

Ethnopharmacological relevanceLiuwei dihuang pills is a famous Traditional Chinese Medicine with various anti-cancer properties. Over 50 pharmaceutical manufacturers produce Liuwei dihuang pills in China and an estimated millions of people around the world orally take it every day. D-glucaro-1,4-lactone (1,4-GL) was quantified to be about 12.0 mg/g in Liuwei dihuang pills and a primary bioactive component of it inhibiting the activity of β-glucuronidase in vivo. 1,4-GL can prevent and effectively inhibit various types of cancer. However, its exact mechanism of action remains unknown. The study would justify the traditional usage of Liuwei dihuang pills against cancers. Aim of the study1,4-GL, a bioactive ingredient derived from Liuwei dihuang pills, a famous Traditional Chinese Medicine, could delay the progression of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. The mechanism underpinning the effect, however, remains poorly understood. Materials and methodsHealthy and HCC rats were treated with or without 1,4-GL (40.0 mg/kg) and 1HNMR-based metabonomic analysis was employed. 10 metabolites in uric acid pathway were quantitatively determined by UPLC-MS/MS. The expression of xanthine dehydrogenase (XDH), SLC2A9 mRNA, and SLC2A9 protein was determined using RT-qPCR and Western Blot. The effect of 1,4-GL on HCC-LM3 cells was verified in vitro. The alterations of ROS activity, SLC2A9 and XDH gene levels were observed in NCTC-1469 cells induced by lipopolysaccharide (LPS) after 1,4-GL treatment. ResultsAfter the intervention of 1,4-GL, improved pathological morphology, liver lesions in HCC rats was observed with restored serum levels of AFP, AST, ALP, γ-GGT and Fisher's ratio. Hepatic metabonomics revealed that puring metabolism were significantly regulated by 1,4-GL in HCC rats. Uric acid, xanthine and hypoxanthine levels were quantified by UPLC-MS/MS and found to be nearly restored to control levels after 1,4-GL treatment in HCC rats. Changes in xanthine oxidase activity, XDH mRNA expression, and SLC2A9 mRNA and protein expression were also reversed. 1,4-GL treatment in LM3 HCC cells were consistent with the results in vivo. Furthermore, oxidative stress indicators such as T-SOD, GSH, CAT and MDA in serum and liver were improved after HCC rats treated with 1,4-GL. In vitro, 1,4-GL was observed to reduce lipopolysaccharide-induced ROS levels in NCTC-1469 cells with enhanced mRNA and protein expression of SLC2A9 and decreased mRNA level of XDH. ConclusionThe protective effects of 1,4-GL against DEN-induced HCC by reducing uric acid and ROS levels due to down-regulation of uric acid production and up-regulation of SLC2A9 expressions. 1,4-GL may represent a novel treatment that improves recovery from HCC by targeting uric acid-ROS pathway.

Pathological and biochemical investigation of the effects of Silybum marianum against Methomyl damage in broiler liver

This study was aimed to investigate the protective/preventive and/or curative effects of Silybum marianum seed powder against Methomyl toxication by examining some biochemical parameters and pathological changes hepatic in broiler chicks fed with feeds supplemented with Methomyl and S. marianum seed powder. For this purpose, 4 different groups, each containing 32 animals, were used; Control group (CONT), Methomyl group (MET), S. marianum seed powder group (SMT) and Methomyl + S. marianum seed powder group (MET+SMT). In the study, Methomyl was added to the feeds as 20 ppm and S. marianum seed powder as 10 g·kg-1. The trial period was planned as 28 days, and necropsies of animals from each group were performed daily, and samples were taken for histopathology and biochemistry. In the study, liver enzyme activities and liver tissue oxidative stress markers GPx, MDA and SOD values were found to be similar in the CONT and SMT groups, but statistically higher in the MET group. In the MET+SMT group, the increased parameters were lower than the MET group. The histopathological examinations of liver sections, hyperemia, hemorrhage, hydropic degeneration and fatty changes of hepatocytes, focal necrosis, dissociation of remark cords, mononuclear cell infiltration in the portal area and bile ducts hyperplasia were detected. It has been observed that S. marianum given for preventive/healing purposes reduces histopathological damage and contributes positively in all groups. It has been concluded that S. marianum can be added to poultry diets against Methomyl residues or contamınatıons according to thıs study.

RES-CMCNPs Enhance Antioxidant, Proinflammatory, and Sensitivity of Tumor Solids to γ-Irradiation in EAC-Bearing Mice.

Resveratrol (Res) is a bifunctional compound found in numerous plants, including grapes and mulberries. Nanotechnology has promising applications in medicine. The ability of various nanomaterials to serve as radiosensitizers against tumor cells were reported in several manuscripts. The present investigation aimed to assess the antitumor and radiosensitizing effects of Res-CMCNPs on EAC-bearing mice. </P> Methods: Res-CMCNPs have been developed using the CMC emulsification cross-linking technique. Entrapment efficiency (%), particle size, Polydispersity index and ZETA potential, UV, FTIR spectra, and drug release were evaluated and described for RES-CMCNPs. The radiosensitizing properties of RES-CMCNPs were also evaluated in vitro and in vivo against EAC-carrying rodents. The LD50 of Res-CMCNPs was estimated and its 1/20 LD50 was prepared for treating EAC transplanted mice. </P> Results: The results revealed that the Res-CMCNPs exhibited a high entrapment efficiency (85.46%) and a size of approximately 184.60 ±17.36 nm with zeta potential value equals -51.866 mv. Also, the UV spectra of Res and Res-CMCNPs have strong absorption at 230 and 250 nm. The percentage of resveratrol release at pHs 5.8 and 7.4 was found to be 56.73% and 51.60 %, respectively, after 24 h at 100 rpm. Also, the FTIR analysis confirmed the chemical stability of resveratrol in Res-CMCNPs cross-linking. The IC50 values of Res-CMCNPs against EAC cells viability were 32.99, 25.46, and 22.21 µg after 24-, 48- and 72 h incubation, respectively, whereas those of ResCMCNPs in combination with γ-irradiation after 6-, 10 and 12-mins exposure were 24.07, 16.06 and 7.48 µg, respectively. Also, the LD50 of Res-CMCNPs was 2180 mg/kg.b.w. The treatment of EAC-bearing mice with Res-CMCNPs plus γ-irradiation improved plasma levels of NO, caspase-3, P53 and NF-kB levels as well as liver MDA, GSH, SOD, CAT, LT-B4, aromatase, Bax, Bcl2 and TGF-β levels and exhibited more significant anticancer activity than administration of ResCMCNPs and/or exposure to γ-irradiation individually. On the other hand, administration of ResCMCNPs in combination with γ-irradiation attenuated liver mRNAs (21, 29b, 181a, and 451) gene expression. </P> Conclusion: Grafting resveratrol onto carboxymethyl chitosan appears to be a promising strategy for cancer therapy as a radiosensitizer by potentiating tumor cells' sensitivity to radiation by improving levels of proinflammatory features and antioxidant biomarkers.

Cynara Cardunculus Flavonoids-rich Fraction Alleviates Liver Injury in Mice Overconsumed Fructose Model.

Non-alcoholic Fatty liver disease (NAFLD) is becoming a major global health burden in the world. Cynara cardunculus is an edible plant growing wild in the North of Algeria. Its potential as a source of health-promoting compounds is still underexplored. This study aimed to explore the preventive effect of Cynara cardunculus (C.cardunculus) on the NAFLD model. Total flavonoid contents (TFC) and in vitro antioxidant effects of butanolic (n- BuTOH) and ethyl acetate (EtOAc) fractions on scavenging the ABTS+ radical, inhibition of lipid peroxidation and reducing power proprieties were assessed. The n-ButOH fraction showed the highest TFC and antioxidant capacity in all realized assays. This fraction is used for anti- NAFLD experiments. Adult male Albinos mice were divided into four groups. Group 1 was normal control. Group 2 was watered with 30% of fructose for three weeks to induce the NAFLD model. Group 3 and Group 4 were co-treated with C. cardunculus n-ButOH fractions and Atorvastatin, respectively for three weeks. Blood and livers were collected for biochemical and histological analysis. The C. cardunculus n-ButOH fractions significantly restored levels of transaminases, triglycerides, cholesterol, LDL, glucose and uric acid. The n-ButOH fraction exerted an improving effect on the body and liver weight and liver index. It also significantly corrected the imbalance in liver MDA and GSH levels. The n-ButOH fractions further ameliorated abnormalities in liver histology through suppression of lipid droplet accumulation. This research proves that the flavonoid-rich fraction of C. cardunculus has protective activity against high fructose intake in mice via reversing hyperlipidemia and boosting liver antioxidant capacity.

The effects of short-time air pollution, SO2, and ozone on biochemical, histo-pathological, oxidative stress, and carcinogenesis related genes expressions in the liver of the rats.

Air pollution is a universal issue and has significant deleterious effects on both human health and also environment. The important indicators of air pollution include ozone (O3), particulate matter (PM), nitrogen dioxide (NO2), and sulfur dioxide (SO2). This research aims to investigate the impacts of ambient air pollution (AAP), SO2, and O3 on oxidative stress parameters, liver tissue histopathology, and expression of some carcinogenesis-related genes in the hepatic tissue of rats. 32 Wistar rats were randomly allocated to four groups: the control group, the AAP group, the SO2 group (10 ppm), and the ozone group (0.6 ppm). Over a period of five consecutive weeks, the rats were exposed to the specified pollutants for 3 h daily; liver tissues were harvested and instantly fixed with formalin. Pathological changes were assessed in the tissue samples. Additionally, the RT-qPCR technique was utilized to investigate Expression alterations of BAX, p-53, BCL2, caspase-3, caspase-8 and caspase-9. Furthermore, 30 milligrams of hepatic tissues were extracted to assess the activities of oxidative stress enzymes. The liver catalase and MDA activity were elevated in the air pollution (p < .05). Also, liver GPx activity in air pollution and ozone groups was significant in comparison to the control group (p < .05). The SO2 group exhibited severe lesions in histopathology examinations. The findings revealed an alteration in liver histopathology, an induction of oxidative stress, and the expression of some apoptosis-related genes in hepatic tissues after exposure to AAP, SO2, and O3.

Effects of Complex Antioxidants Added to Chicken Diet on Growth Performance, Serum Biochemical Indices, Meat Quality, and Antioxidant Capacity

This study aimed to evaluate the effects of diets supplemented with various levels of complex antioxidants (CA) containing tertiary butylhydroquinone (TBHQ) and tea polyphenols (TP) on growth performance, meat quality of breast and leg muscles, serum biochemistry, and antioxidant capacity of serum, liver, breast meat, jejunum, and ileum in broilers. A total of 600 one-day-old Arbor Acres male broilers with similar body weights were randomly divided into three groups (10 replicates/group, 20 broilers/replicate). Birds in the three experimental groups were fed a basal diet with CA at 0, 300, and 500 mg/kg. The results showed that supplementing with 300 mg/kg CA significantly increased (p &lt; 0.05) 42 d BW and 22–42 d ADG, and markedly decreased (p &lt; 0.05) 22–42 d F: G ratio in comparison to the control group. Birds fed a diet with 300 mg/kg CA had a higher (p &lt; 0.05) pH of chicken meat at 24 h and 48 h post mortem and lower (p &lt; 0.05) yellowness values (b*) of chicken meat at 45 min and 24 h post mortem, along with a lower (p &lt; 0.05) cooking loss. Supplementing with 300 mg/kg CA significantly increased (p &lt; 0.05) serum and liver T-SOD activity, serum T-AOC level, as well as jejunual GST activity, and significantly decreased (p &lt; 0.05) liver MDA content when compared with the control group. These results indicate that diet supplementation with 300 mg/kg CA containing TBHQ and TP could improve growth performance and meat quality by increasing the antioxidant capacity of broilers.

The mechanism of polystyrene nanoplastics hepatotoxicity in zebrafish (Danio rerio)

The mass production of plastics and improper disposal of plastic waste has led to their widespread presence in the ecosystem. Plastics entering the natural environment degrade into irregularly shaped and differently sized nanoplastics (NPs), exacerbating global pollution. The research object to study toxic mechanisms of the liver polystyrene nanoplastics (PS NPs) of zebrafish, providing key scientific insights for the environmental risk assessment of NPs. The zebrafish were exposed to different concentrations with a particle size of 100 nm PS NPs containing Eu, and the accumulation of nanoplastics in each tissue/organ was quantified. The mechanism of liver toxicity of nanoplastics to zebrafish was explored. Where the mass of PS NPs was linearly related to the mass of Eu with R2 = 0.999. PS NPs were accumulated in gills, ovaries, liver, spleen, intestine, kidney, skin, muscle and brain. The top three accumulations were: intestine &gt; gills &gt; liver. The histopathological analysis of liver indicated that 0.1 mg/L and 1 mg/L PS NPs caused increased liver inflammation. 0.1 mg/L PS NPs significantly increased the activity of SOD and the content of ROS and MDA in liver. 1 mg/L PS NPs significantly increased the activity of SOD, CAT and GSH and the content of MDA in liver, while significantly decreased the content of ROS. These results will improve the appreciation of the cumulative impact of PS NPs and the mechanism of toxicity on target organs in organisms.

Elevation of MDA Levels and Change in Histopathological of Balb/c Mice's Liver on Acute Test of Fortification of Ethanolic Roselle Flower (Hibiscus sabdariffa L.) Extract in Yogurt

The bioactive peptides in yogurt and flavonoids in roselle flower extract have antioxidant activity that benefits the body's health. Roselle flower extract supplementation at a 5000 mg/kg dose is known not to cause death in rats. However, the toxic dose and safety of consuming fortification of roselle and yogurt have not been studied. This study aimed to determine the effect of fortification of roselle flower extract and yogurt on liver histopathology and MDA levels in the liver of the mice. Twenty male Balb/c mice (Mus musculus) were divided into four groups: healthy and untreated (control) and groups of treatment that were given fortification of ethanolic roselle flower extract and yogurt. Each treatment group was given a single dose (1000, 1400, and 7000 mg/kg) of the extract orally and observed for any clinical signs, change of habit, and death for 14 days, and they were euthanized the day after. MDA levels were measured using the Thiobarbituric Acid-Reactive Substance (TBARS) method. Hematoxylin-Eosin staining was used for histopathology and analyzed with the Knodell scoring method. The MDA levels were analyzed using one-way Analysis of Variance (ANOVA) and post-test (α=0.05). The liver degeneration and focal necrosis were analyzed statistically using the Kruskal Wallis and Mann Whitney post-test (α=0.05). The 1400 and 7000 mg/kg dosage elevated the liver MDA levels (p&lt;0.05). Degeneration and focal necrosis scores in the liver due to fortification administration were escalated at all doses compared to the control group (p&lt;0.05).

Therapeutics of L. Lanceolata and V. Doniana on Alcohol Induced Hepatic Pathology

Additive and stimulative properties of alcohol encourage large intake. Notwithstanding, chronic alcohol consumption causes severe hepatic damage, that alters normal biological function of the liver. The aim of this research was to assess the effects of Lophira lanceolata and Vitex doniana extracts on alcohol induced hepatotoxicity using rat model by examining liver serum enzymes (AST, ALT, ALP), lipid peroxidation level, antioxidant enzyme activity and haematological parameters. Thirty Wister rats weighing 70 to 120g were placed in six groups of fives per group. The negative control and treatment groups were familiarized with alcohol (42%) in drinking water before oral administration of 42% consumable alcohol (v/v, 1ml/100g body weight) for nine days. Afterward, the treatment groups were administered 600mg/kg body weight extracts of Lophira lanceolata, Vitex doniana and Vitamin C (as standard drug). Body weight and behavioural characters were monitored during the period. It was observed that, rats in the negative and treatment groups showed significant depletion in weight and negative changes in behaviour. Furthermore, biochemical assessment revealed significant elevated levels of liver serum enzymes (ALT, AST, ALP) activity, total and direct bilirubin, MDA, SOD and CAT while GSH and haematological parameters were significantly depleted at p&lt;0.05. However, the treated groups revealed significant reduction in the liver enzymes, MDA, SOD and CAT while GSH activity and haematological parameters were significantly increased. In conclusion, both extracts have ameliorative and antioxidant properties that could mitigates chronic alcohol hepatotoxicity.

Dietary lipid levels affect growth performance, lipid metabolism, antioxidant and immune status of Amur sturgeon, Acipenser schrenckii

The proper lipid content in the diets is crucial for fish growth and health. However, the appropriate lipid requirement of Amur sturgeon has not been systematically studied. This study was aimed to explore the effects of dietary lipid levels on growth performance, lipid metabolism, antioxidant and immune status of juvenile Amur sturgeon (Acipenser schrenckii). Six isonitrogenous diets containing 5.11% (L5), 8.87% (L9), 12.96% (L13), 16.93% (L17), 20.84% (L21) and 24.88% (L25) lipid were fed to Amur sturgeon (4.16 ± 0.07 g) for 10 weeks. The fish in L21 group had the highest growth, feed utilization and survival rate. Based on the broken-line regression analysis of WGR, the lipid requirement for juvenile Amur sturgeon was 20.31%. HSI, hepatic crude lipid content and serum TG, TC and LDL-C contents elevated significantly with the increase of dietary lipid. Higher hepatic SOD, Anti-O2.- were found in L21 group, while MDA in both serum and liver maintained an upward trend with dietary lipid increase. The expression levels of fasn and lpl were suppressed when dietary lipid levels reached or exceeded 16.93%. While cpt1α and pparα were up-regulated, and peaked in L21 group, but down-regulated in L25 group. The expression level of il1β was on the rise as dietary lipid increased, but il10 and tgfβ1 showed a downward trend in high lipid groups. In conclusion, based on WGR, a lipid level of 20.31% in the diet was optimal for juvenile Amur sturgeon. Low (5.11%−12.96%) or high lipid (24.88%) diet decreased growth, feed utilization and survival rate. High lipid (24.88%) diet induced excessive lipid deposition, leading to intense oxidative stress, lipid metabolism disorder and inflammation.

Dietary Supplementation of Mixed Organic Acids Improves Growth Performance, Immunity, and Antioxidant Capacity and Maintains the Intestinal Barrier of Ira Rabbits.

The aim of this study was to investigate the effects of mixed organic acids (MOAs) on growth performance, immunity, antioxidants, intestinal digestion, and barrier function in Ira rabbits. A total of 192 weaned male Ira rabbits at 35 days of age were randomly assigned to four groups with six replicates of eight rabbits each. The rabbits in the control group (CON) were fed a basal diet, and the antibiotic group (SAL) was fed a basal diet supplemented with 60 mg/kg salinomycin. The test groups were fed a basal diet supplemented with 1000 mg/kg and 2000 mg/kg MOAs (MOA1 and MOA2, respectively). The experiment lasted for 55 days. The results showed that the ADG of Ira rabbits in the SAL group and MOA1 group was higher than that in the CON group (p < 0.05). The serum IL-6 and liver MDA levels of Ira rabbits in the SAL group, MOA1 group, and MOA2 group were lower than those in the CON group (p < 0.05). In addition, sIgA levels in the jejunal mucosa of Ira rabbits in the SAL group and MOA1 group were increased compared with those in the CON group (p < 0.05). Compared with the CON group, the gene expression of IL-6 was decreased (p < 0.05) in the jejunal mucosa of Ira rabbits in the SAL, MOA1, and MOA2 groups, while the gene expression of IL-1β tended to decrease (p = 0.077) and the IL-10 content tended to increase (p = 0.062). Moreover, the gene expression of ZO-1 in the jejunal mucosa of Ira rabbits was elevated in the MOA1 group compared with the CON group (p < 0.05). In conclusion, dietary supplementation with MOAs can improve growth performance, enhance immune function and antioxidant capacity, and maintain the intestinal barrier in weaned Ira rabbits.

Beneficial effects of silibinin on serum lipids, bile acids, and gut microbiota in methionine-choline-deficient diet-induced mice.

Silibinin (SIL) is a flavonoid lignin isolated from the fruit and seeds of silybum marianum that exhibits good therapeutic potential for NASH. However, the effects of SIL on serum lipids, bile acids (BAs), and gut microbiota (GM) in NASH mice remain unknown. The present work aimed to explore the beneficial effects of SIL supplementation on serum lipids, bile acids, and gut microbiota in MCD mice. After male C57BL/6 mice were fed with a methionine-choline deficient (MCD) diet and simultaneously gavaged with SIL (20 mg/kg. d) for 8 weeks, the pathological changes of liver tissue were observed by oil red O, haematoxylin-eosin, and Masson tricolor staining; the levels of serum AST and ALT, and liver TG and MDA were detected by assay kits; metabonomics and 16S rDNA sequencing were used to analyze the composition of serum lipids and BAs and the abundance of GM; and the mRNA expression levels of hepatic genes related to BAs homeostasis were detected by RT-qPCR. The results indicated that SIL treatment decreased the levels of 26 lipids (including four arachidonic acids, seven FFAs, 12 acyl carnitines, and three GPs) and two BAs (23-DCA, GLCA), while Dubosiella increased the levels of 10 lipids (including TxB3, PG16:0_18:1, Cer t18:0/24:0 and 7 TGs), five BAs (β-MCA, α-MCA, UDCA, 3-oxo-DCA and HCA), and two GMs (Verrucomicrobiota and Akkermansiaceae) of MCD mice, but had no significant effect on the mRNA expression of CYP7A1, CYP27A1, Bsep, Mrp2, Ntcp, or Oatp1b2. Therefore, influencing GM composition and then regulating the levels of serum lipids and BAs through enterohepatic axis should be an important mechanism of SIL-induced alleviative effect on MCD mice. More importantly, we found that SIL had a good coordination in regulating the abundance of GM and the contents of serum lipids and BAs in MCD mice, that is, when the abundance of probiotics was up-regulated, the content of beneficial unsaturated fatty acids in serum was up-regulated, while the serum levels of harmful lipids and BAs were down-regulated. The alleviating effect of SIL on NASH may be closely related to the correction of intestinal bacteria disorder, serum bile acid, and lipid metabolic disturbance in mice.

The potential protective effect of liraglutide on valproic acid induced liver injury in rats: Targeting HMGB1/RAGE axis and RIPK3/MLKL mediated necroptosis.

Valproic acid (VPA) is a commonly used drug for management of epilepsy. Prolonged VPA administration increases the risk of hepatotoxicity. Liraglutide is a glucagon-like peptide 1 receptor (GLP-1R) agonist that act as a novel antidiabetic drug with broad-spectrum anti-inflammatory and antioxidant effects. This study tested the protective effect of liraglutide against VPA-induced hepatotoxicity elucidating the possible underlying molecular mechanisms. Forty adult male rats were allocated in to four equally sized groups; Group I (control group) received oral distilled water and subcutaneous normal saline for 2 weeks followed by subcutaneous normal saline only for 2 weeks. Group II (liraglutide group) received subcutaneous liraglutide dissolved in normal saline daily for 4 weeks. Group III (valproic acid-treated group) received sodium valproate dissolved in distilled water for 2 weeks. Group IV (Combined valproic acid & liraglutide treated group) received valproic acid plus liraglutide daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration. The hepatic index was calculated. Serum AST, ALT, GGT, and ALP activities were estimated. Hepatic tissue homogenate MDA, GSH, SOD, HMGB1, MAPK, RIPK1, and RIPK3 levels were evaluated using ELISA. However, hepatic RAGE and MLKL messenger RNA expression levels using the QRT-PCR technique. Hepatic NF-κB and TNF-α were detected immunohistochemically. Results proved that liraglutide coadministration significantly decreased liver enzymes, MDA, HMGB1, MAPK, RIPK1 RIPK3, RAGE, and MLKL with concomitant increased GSH and SOD in comparison to the correspondent values in VPA-hepatotoxicity group. Conclusions: Liraglutide's protective effects against VPA-induced hepatotoxicity are triggered by ameliorating oxidative stress, inflammation, and necroptosis.

Investigation of the effects of nanoemulsion formulation containing glycyrrhizin in Streptozotocin-induced diabetic rats

This study aims to prepare and in vitro and in vivo characterize nanoemulsion formulation containing GLY (GLY-NE). Firstly, the NE formulation was prepared and in vitro characterized. Later, the hypoglycemic and antioxidant effects of GLY-NE formulations in STZ-induced diabetic rats were investigated. Also, histopathological evaluation was performed. The droplet sizes of blank NE (B-NE; 110.75 ± 9.60) and GLY-NE (126.44 ± 3.86) were in the nano-size range. Furthermore, PDI values of B-NE and GLY-NE formulations were less than 0.3. The zeta potential values of B-NE and GLY-NE were (−)19.02 ± 1.18 mV and (−) 20.52 ± 0.83 mV, respectively. At the end of the 21st day, comparing the same dose groups administered GLY or GLY-NE, the blood glucose levels of the diabetic rats administered GLY-NE (D-GLY-NE groups) were lower than the diabetic rats administered GLY (D-GLY groups). Furthermore, the blood glucose level of D-GLY-NE (40 mg/kg) was significantly lower than that of D-GLY (40 mg/kg; p < 0.05). Compared with the diabetic control, the serum ALT and AST levels and liver MDA of the diabetic rats treated with GLY or GLY-NE (for all doses) were significantly decreased, while the liver SOD activity and GSH levels were significantly increased (p < 0.05). The NE formulation may be a potential dosage form for oral delivery of GLY.

Effects of Rutin and Selenomethionine in Selenium-Enriched Tartary Buckwheat Roasted Grain Tea on Glucose and Lipid Metabolism in db/db Mice

Rutin and selenomethionine in selenium-enriched Tartary buckwheat roasted grain tea have certain effects on glucose and lipid metabolism in type II diabetes mellitus, but the mechanism of intervention is still unclear. This study utilized selenium-enriched Tartary buckwheat tea, rutin, and selenomethionine as research materials, with db/db mice serving as the research subjects. Diabetes control (DC), positive control group (PC), rutin group (RC), selenomethionine group (SC), low dose selenium-enriched Tartary buckwheat tea group (TBG-L), medium dose group (TBG-M) and high dose group (TBG-H) were set up. The effects of selenium enriched Tartary buckwheat tea, rutin and selenomethionine on glucose and lipid metabolism in db/db mice were investigated by blood biochemical analysis, liver function and oxidative stress measurement, histopathology and glycogen determination and mRNA expression analysis. Selenium-enriched Tartary buckwheat tea and its active ingredients rutin and selenomethionine can reduce fasting blood glucose and glucose resistance in db/db mice. Dyslipidemia of db/db mice was improved to some extent. The changes of MDA, CAT, T-SOD and GSH-Px enzyme activities in liver also indicate that TBG can improve the oxidative stress of liver and exert liver protection activities. Selenium-enriched Tartary buckwheat tea, rutin and selenomethionine can mediate glycogen storage by increasing glycogen synthesis and inhibiting gluconeogenesis in the liver of diabetic db/db mice, and can effectively mediate the expression of related genes during gluconeogenesis. Among the selenium-enriched Tartary buckwheat groups, the effect of TBG-H group was the most obvious, which indirectly indicated that rutin and selenomethionine could play synergistic roles in gluconogenesis.

Regulatory Effects and Mechanisms of L-Theanine on Neurotransmitters via Liver-Brain Axis Under a High Protein Diet.

Excessive protein intake causes liver and brain damage and neurotransmitter disorders, thereby inducing cognitive dysfunction. L-theanine can regulate the neurotransmitter content and show great potential in liver and brain protection. However, it remains unclear whether l-theanine effectively regulates neurotransmitter content under high-protein diet. A 40-day feeding experiment was performed in Sprague Dawley rats to investigate the regulatory effects and mechanisms of l-theanine on neurotransmitters via liver-brain axis in high-protein diets. The results showed that a 30% protein diet increased the liver and brain neurotransmitter content while maintaining the normal structure of liver and the hippocampal CA1 of brain and improving the autonomous behavior of rats. In contrast, 40% and 50% protein diets decreased the content of neurotransmitters, affected autonomous behavior, destroyed the hippocampal CA1 of brain structure, increased hepatic inflammatory infiltration, lipid degeneration, and hepatocyte eosinophilic change in liver, increased liver AST, ALT, MDA, CRP, and blood ammonia level, and decreased liver SOD and CAT level. However, l-theanine improved liver and brain neurotransmitter content, autonomous behavior, liver and hippocampal brain structure, and liver biochemical indicators in 40% and 50% protein diets. To explore how LTA can eliminate the adverse effects of a high-protein diet, we analyzed different metabolites and proteomes and using western blotting for validate quantitatively. We found that l-theanine regulates the activity of PF4 and G protein subunit alpha i2, increases the content of brain-derived neurotrophic factor and dopamine under a 20% protein diet. In addition, l-theanine can activate the adenylate cyclase-protein kinase A pathway through the protein alpha/beta-hydrolase domain protein 12 to regulate the content of neurotransmitters under a 40% protein diet, thereby exerting a neuroprotective effect.