Liver GSH Research Articles

The Hepatoprotective Effects of Camellia sinensis on Cisplatin-Induced Acute Liver Injury.

Acute liver injury is an increasing global health problem. It is a widespread side effect of cisplatin treatment in the clinic and can lead to liver failure if not treated promptly. Previous studies have revealed that green tea can protect some organs from treatments. However, the potential of white tea to prevent the negative effects of acute liver injury has not been addressed so far. The purpose of this study was to investigate the reduction in cisplatin-induced liver injury in rats receiving white tea. Female Sprague Dawley rats with similar weight were selected in this study. Twenty-four rats were divided into three groups of eight animals each and ad libitum nutrition was provided. The control and cisplatin groups were given tap water only, while the white tea + cisplatin group received white tea at a 0.5% weight/volume concentration for four weeks. At the end of the fourth week, the white tea + cisplatin group and the cisplatin group received a single dose of cisplatin (7 mg/kg) via the intraperitoneal route. Five days after that procedure, the rats were anesthetized. Liver tissues and blood samples were collected, which were used for biochemical and histopathological analyses. According to biochemical results, liver tissue MDA and GSH, serum ALT, and AST levels significantly increased in the cisplatin group compared to the control group. Compared with the cisplatin group, although MDA, AST, ALT, and GSH levels were lower in the white tea + cisplatin group, only GSH levels were statistically different. The examination of histopathological and immunohistochemical findings revealed apoptotic cells, vascular congestion, and sinusoidal dilatation in the cisplatin group compared to the control group. This adverse event decreased in the white tea + cisplatin group compared to the cisplatin group. In conclusion, white tea exhibits an ameliorating effect on cisplatin-induced liver injury.

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.

The Protective Role of Nigela Sativa Volatile Oil on Antioxidant and Oxidative Stress Enzymes

Hepatotoxicity is the outcome of a paracetamol overdose.In this study, 40 adult male rats, weighing 180–260 gm and aged between 9 and 13 weeks, were given doses of Nigela sativa oil and their liver enzymes were examined to see how paracetamol affected them. The rats were kept in an environment at a temperature of 25 Co in an animal house. ,There were four groups of rats, and food was provided for them. (G). (G1) The only injections given to the control group are food and regular saline (0.9% of the time). (G2) 200 mg/kg of N. sativa and (G3) 400 mg/kg of paracetamol Addition of 400 mg/kg body weight of paracetamol. supplying 300 mg/kg B.W. of N. sativa to (G4)400 milligrams/kg B.W. of aspirin. Rat G2, GPT 87.80 IUL, and GOT hepatic enzyme concentration (129.32 IUL) all exhibit significant increases in comparison to the control. Furthermore, the levels of the liver GSH enzyme in rats (G2 )1.24 IUL shown a substantial increase, whereas G3 ( GOT ) 91.9 IUL, (GPT )76.70 IUL, and group (G4) GOT 109.88 IUL and enzyme (GPT ) 55.66 IUL exhibited significant declines as compared with control. While MDA enzyme in rats G2 (0.259 IUL) shows a major increase in comparison to the control, rats G3 (0.139 IUL) and G4 (0.112) show a noticeable decrease in comparison to G2. While body weight indicates that G2's outcomes are significantly lower than those of the other three groups. Groups G3 (2.55 gm) and G4 (2.7 gm) demonstrated a significant rise in liver weight compared to controls and G2, whereas groups G2 (24.23 gm) demonstrated a significant increase in liver weight compared to controls and group G2. Male rats in groups G2 (1.7 gm) demonstrated a significant drop in liver weight compared to controls.

Reparative potentials of commensal-derived cellular components in juvenile Lateolabrax maculatus fed high soybean meal diet: Insight into growth performance, immunity, antioxidant capacity and liver health

An eight-week feeding trial was designed to estimate the effects of commensal Bacillus siamensis LF4-derived whole cell wall (CW), cell wall protein (CWP), lipoteichoic acid (LTA) and peptidoglycan (PGN) supplementation in a high soybean meal (SM) diet on the growth, immunity and liver health of spotted seabass (Lateolabrax maculatus). Fish continuously fed low SM (containing 16 % SM) and high SM (containing 40 % SM) diets were served as positive (LSM) and negative (HSM) control, respectively. After feeding high SM diet for 28 days, fish were fortified with B. siamensis LF4-derived CW, CWP, LTA or PGN until 56 days. The results showed that CW, LTA, and PGN application significantly increased FBW, WGR, and SGR (P<0.05), but not affect CF, VSI, HSI, IFR, ILI, and ISI (P＞0.05) in spotted seabass (L. maculatus) fed with high SM diet. Distal intestinal protease activity reduction caused by dietary high SM inclusion was significantly repaired when spotted seabass (L. maculatus) fortified with LTA and PGN (P<0.05). CW, LTA and PGN administration effectively increased serum immunity by enhancing ACP activity and C3, C4, IgM contents and reduced IL-1β content in serum of spotted seabass (L. maculatus) fed high SM diet (P<0.05). Significantly decreased serum MDA content in groups CW, LTA and PGN and significantly increased liver GSH content in group CWP were observed as compared to those in group HSM (P<0.05). Dietary CW, LTA and PGN supplementation, rather than CWP, repaired SM-induced liver injury by improving liver morphology and significantly reducing GOT and GPT activities (P<0.05). In summary, CW, LTA and PGN derived from B. siamensis LF4 effectively repaired SM-induced growth, feed utilization, immunity suppression and liver injury in spotted seabass (L. maculatus).

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.

Pleurotus eryngii root waste and soybean meal co-fermented protein improved the growth, immunity, liver and intestinal health of largemouth bass (Micropterus salmoides)

The present study aimed to evaluate the effect of king oyster mushroom (Pleurotus eryngii) root waste and soybean meal co-fermented protein (CFP) on growth performance, feed utilization, immune status, hepatic and intestinal health of largemouth bass (Micropterus salmoides). Largemouth bass (12.33 ± 0.18 g) were divided into five groups, fed with diets containing 0 %, 5 %, 10 %, 15 % and 20 % CFP respectively for 7 weeks. The growth performance and dietary utilization were slightly improved by the supplementation of CFP. In addition, improved immunoglobulin M (IgM) content and lysozyme activity in treatments confirm the enhancement of immunity in fish by the addition of CFP, especially in fish fed 20 % CFP (P < 0.05). Furthermore, CFP significantly improved liver GSH (glutathione) content in groups D10 and D15 (P < 0.05), and slightly improved total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity while slightly reduced malondialdehyde (MDA) content. Simultaneously, the upregulation of lipolysis-related genes (PPARα, CPT1 and ACO) expression and downregulation of lipid synthesis-related genes (ACC and DGAT1) expression was recorded in the group D20 compared with the control (P < 0.05), which were consistent with the decreased liver lipid contents, suggests that lipid metabolism was improved by CFP. In terms of intestinal structural integrity, ameliorated intestinal morphology in treatments were consistent with the upregulated Occludin, Claudin-1 and ZO-1 genes expression. The intestinal pro-inflammatory cytokines (TNF-α and IL-8) expression were suppressed while the anti-inflammatory cytokines (IL-10 and TGF-β) were activated in treatments. The expression of antimicrobial peptides (Hepcidin-1, Piscidin-2 and Piscidin-3) and intestinal immune effectors (IgM and LYZ) were slightly up-regulated in treatments. Additionally, the relative abundance of intestinal beneficial bacteria (Firmicutes) increased while the relative abundance of potential pathogenic bacteria (Fusobacterium and Proteobacteria) decreased, which indicated that the intestinal microbial community was well-reorganized by CFP. In conclusion, dietary CFP improves growth, immunity, hepatic and intestinal health of largemouth bass, these data provided a theoretical basis for the application of this novel functional protein ingredient in fish.

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.

Beneficial Effects of Probiotics on Liver Injury Caused by Chronic Alcohol Consumption

Alcoholic liver injury is a serious risk to human health. Probiotics have become a popular form of treatment. Lacticaseibacillus casei Grx12 and Limosilactobacillus fermentum Grx07 isolated from the gut of long-lived people in Rugao, Jiangsu, were studied to determine their protective effects and possible mechanisms of action on alcoholic liver injury. The results showed that rat serum ALT and AST were restored, and liver injury was reduced after the probiotics intervention. The level of antioxidant enzymes and antioxidants such as SOD, GSH and GSH-Px in the rat liver was significantly increased (p &lt; 0.05), which reduces the level of MDA, a peroxidation product in the liver, and thus alleviates liver oxidative stress. L. casei Grx12 and L. fermentum Grx07 also could significantly enhance the expression of Nrf2 protein in the rat liver to regulate the anti-oxidative stress response in the body and cells (p &lt; 0.05). The levels of ADH, Na+-K+-ATPase and Ca2+-ATPase in the rat liver were significantly increased (p &lt; 0.05), which enhanced the body’s metabolism of alcohol. The rat serum LPS and liver TNF-α, IL-6, VEGF, TGF-β1 and NF-κB levels were significantly reduced (p &lt; 0.05), indicating that the probiotics could relieve liver inflammation. The results of this study indicate that L. casei Grx12 and L. fermentum Grx07 have certain protective effects on alcoholic liver injury in rats, likely because of their antioxidant properties and ability to prevent oxidative stress and relieve inflammation.

Dietary glycine supplementation enhances glutathione availability in tissues of pigs with intrauterine growth restriction.

This study tested the hypothesis that dietary supplementation with glycine enhances the synthesis and concentrations of glutathione (GSH, a major antioxidant) in tissues of pigs with intrauterine growth restriction (IUGR). At weaning (21 d of age), IUGR pigs and litter mates with normal birth weights (NBW) were assigned randomly to one of two groups, representing supplementation with 1% glycine or 1.19% l-alanine (isonitrogenous control) to a corn- and soybean meal-based diet. Blood and other tissues were obtained from the pigs within 1wk after the feeding trial ended at 188 d of age to determine GSH, oxidized GSH (GSSG), and activities of GSH-metabolic enzymes. Results indicated that concentrations of GSH + GSSG or GSH in plasma, liver, and jejunum (P < 0.001) and concentrations of GSH in longissimus lumborum and gastrocnemius muscles (P < 0.05) were lower in IUGR pigs than in NBW pigs. In contrast, IUGR increased GSSG/GSH ratios (an indicator of oxidative stress) in plasma (P < 0.001), jejunum (P < 0.001), both muscles (P < 0.05), and pancreas (P = 0.001), while decreasing activities of γ-glutamylcysteine synthetase and GSH synthetase in liver (P < 0.001) and jejunum (P < 0.01); and GSH reductase in jejunum (P < 0.01), longissimus lumborum muscle (P < 0.01), gastrocnemius muscle (P < 0.05), and pancreas (P < 0.01). In addition, IUGR pigs had greater (P < 0.001) concentrations of thiobarbituric acid reactive substances (TBARS; an indicator of lipid peroxidation) in plasma, jejunum, muscles, and pancreas than NBW pigs. Compared with isonitrogenous controls, dietary glycine supplementation increased concentrations of GSH plus GSSG and GSH in plasma (P < 0.01), liver (P < 0.001), jejunum (P < 0.001), longissimus lumborum muscle (P = 0.001), and gastrocnemius muscle (P < 0.05); activities of GSH-synthetic enzymes in liver (P < 0.01) and jejunum (P < 0.05), while reducing GSSG/GSH ratios in plasma (P < 0.001), jejunum (P < 0.001), longissimus lumborum muscle (P < 0.001), gastrocnemius muscle (P = 0.01), pancreas (P < 0.05), and kidneys (P < 0.01). Concentrations of GSH plus GSSG, GSH, and GSSG/GSH ratios in kidneys were not affected (P > 0.05) by IUGR. Furthermore, glycine supplementation reduced (P < 0.001) TBARS concentrations in plasma, jejunum, muscles, and pancreas. Collectively, IUGR reduced GSH availability and induced oxidative stress in pig tissues, and these abnormalities were prevented by dietary glycine supplementation in a tissue-specific manner.

Hypolipidemic and hepatoprotective effects of corn silk extract in nicotine-administered male mice.

This study is done to investigate the hypolipidemic and hepatoprotective effects of corn silk extract in nicotine-administered male mice. Nicotine can induce pathophysiological effects in the liver tissue through oxidative stress and damage cells. Corn silk can improve liver function with its antioxidant effects. In this experimental study, 30 male NMRI mice (25-30 gr) were divided into 5 groups: controls, sham, nicotine 2.5 mg/kg, nicotine+aqueous extract of corn silk 400 mg/kg, and nicotine+methanolic extract of corn silk 400 mg/kg for 1 month. One day after the last nicotine and extracts consumption, the serum samples were performed for biochemical measurement, and the supernatant of the homogenized liver was administered for antioxidant variables assessment. There was no significant difference in the body weight of different groups. Liver weight and GSH decreased in the nicotine group compared to the control group (P<0.05). Triglycerides, total cholesterol, HDL-C, LDL-C, liver enzymes, and MDA increased in the nicotine group compared to the control group (P<0.05). Also, the expansion of sinusoids, the presence of inflammatory cells, and necrosis of liver cells were observed in the nicotine group compared to the control group. Using aqueous and methanolic extracts of corn silk in mice receiving nicotine led to the improvement of the mentioned variables (P<0.05). The results of this study showed that the use of nicotine can lead to the induction of hepatotoxicity. The use of aqueous and methanolic extracts of corn silk improved them through its antioxidant activity.

262 Weaning-Induced Changes in Tissue Cysteine Utilization in Pigs

Abstract Weaning stress in pigs is associated with low and variable feed intake, poor nutrient utilization, and high feed costs. Cysteine is a sulfur amino acid with key roles in pig production, but how cysteine metabolism and requirements are affected by weaning stress should be better defined. The objective of this study was to determine weaning-induced changes in tissue cysteine metabolism. Pigs (initial BW = 7.23 ± 0.68 kg) were either weaned at 21 d age and euthanized at 23 d age (W; n = 9) or remained with the sow and euthanized at 23 d age (NW; n = 9). Weaned pigs were fasted to simulate acute nutritional stress but had free access to water. At euthanasia, blood, liver, jejunum, and ileum tissues were collected. Plasma and tissue amino acids and amino thiols were analyzed by HPLC. The abundance of proteins central to liver cysteine utilization were determined by immunoblot and enzyme activity assays. Glutathione (GSH) concentrations were less in jejunum (1,379 versus 1,720 ± 70 nmol/g; P &amp;lt; 0.01) and ileum (1,497 versus 1,740 ± 74 nmol/g; P &amp;lt; 0.05) in W than NW pigs. However, liver GSH concentration was not different between W and NW pigs (P &amp;gt; 0.10). While cysteine in jejunum and ileum were not affected by weaning (P &amp;gt; 0.10), γ-glutamylcysteine (γ-GC), the immediate precursor of GSH, declined in both jejunum (9.7 versus 14.3 ± 1.4 nmol/g; P &amp;lt; 0.01) and ileum (6.4 versus 11.2 ± 0.8 nmol/g; P &amp;lt; 0.001) in W compared with NW pigs. In liver, cysteine concentration was greater in W compared with NW pigs (417 versus 298 ± 33 nmol/g; P &amp;lt; 0.05). Although liver cysteine was greater in W pigs, liver activity of glutamate cysteine ligase (GCL; 2.49 versus 4.15 ± 0.25 nmol γ-GC/(mg protein•min); P &amp;lt; 0.001) and glutathione synthetase (GSS; 1.54 versus 1.92 nmol GSH/(mg protein•min); P &amp;lt; 0.001), enzymes needed for GSH production, were less in W than NW pigs. Immunoblot analysis of the catalytic subunit of GCL (GCLC; P &amp;lt; 0.05) and modifier subunit of GCL (GCLM; P = 0.057) were also lower in W compared with NW pigs, but GSS was not different between groups (P &amp;gt; 0.10). While plasma taurine was lower in W compared with NW pigs (64 versus 128 ± 7 µmol/L, P &amp;lt; 0.001), liver taurine was greater in W compared with NW pigs (4,726 versus 2,250 ± 471 nmol/g; P &amp;lt; 0.01). Despite an increase systemic and liver availability of cysteine, the rate-limiting amino acid for GSH synthesis, small intestine GSH concentrations decline. This suggests that systemic cysteine is not effectively utilized for gut GSH production in pigs after weaning.

Anti-inflammatory and Antioxidant Effects of Grapefruit Juice on Ulcerative Colitis induced by Acetic Acid in Rats

Grapefruit is commonly consumed around the world due to its nutritional and medicinal properties. Ulcerative colitis (UC) accounts for an inflammatory bowel disease (IBD) accompanied by irritation, recurrent inflammation, and ulceration of the colon's mucosa. Our objective was to assess the antiinflammatory and antioxidant impacts of grapefruit juice (GFJ) in rat with UC induced by acetic acid (AA). There were five groups made up of 35 mature male rats. Group 2 served as a positive control with UC, whereas group 1 was preserved as a negative control. For 8 weeks, groups 3, 4, and 5 received UC while also given 2.5, 5 or 10% of GFJ orally. Feed efficiency ratio (FER), body weight growth (BWG), and feed intake (FI) were computed. From rat eye orbital plexuses blood samples were taken to separate the serum after centrifugation. The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were assessed utilizing serum samples. The antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) in serum were quantified. Serum inflammatory cytokines as tumor necrosis factor alpha (TNFα), interleukin 1 β (IL1 β), IL6 and IL8, as well as triglycerides (TG) and total cholesterol (TC) were measured. In liver homogenate, glutathione (GSH) and malondialdehyde (MDA) were determined. Additionally, histopathology of the colon was accomplished. Our findings specified that GFJ at 10% significantly decreased FI, BWG and FER, cytokines TNFα, IL1 β, IL6 and IL8 and TC and TG. Relative to the positive controls, the rats treated with GFJ exhibited elevated serum concentrations of SOD, GPx, and CAT enzymes. Liver GSH was elevated and MDA was reduced. Histopathological examination of the colon showed that GFJ at 10% reduced ulcerative colitis. Because grapefruit juice has strong anti-inflammatory and antioxidant characteristics and reduces oxidative stress and inflammation in rats, grapefruit juice, at a concentration of 10%, likely protects against ulcerative colitis. Patients with ulcerative colitis may find it helpful to consume grapefruit juice as a beverage.

Ethyl acetate fraction of Mucuna pruriens leaves mitigates diclofenac-induced hepatotoxicity via modulation of biochemical and histological parameters changes in Wistar Rats

Mucuna pruriens contains saponins and flavonoids, which help to decrease cholesterol, treat hypertension, provide protein and vitamins and prevent premature ageing. This research followed the NIH guidelines (NIH publication 85–23, revised in 1996). Rats weighing 200–250 g were assigned into six groups (n = 6), normal saline only (control), normal saline (NS), Ethyl acetate fraction of Mucuna pruriens leaves (EAFMP) (100, 200 and 400 mg/kg) and Silymarin (100 mg/kg) treated orally for five days, diclofenac (DFN) was administered on days 3 and 4 via intraperitoneal route, biochemical and histology parameters were determined in serum and liver. This research revealed that treatment with EAFMP reversed the elevation of liver enzymes, total bilirubin, LDL and total cholesterol and lipid peroxidation; liver SOD, GSH, and CAT were elevated in EAFMP and Silymarin groups. The hepatic histological lesions in EAFMP were reduced in a dose-dependent manner. This research shows that EAFMP attenuates the deleterious effect of diclofenac-induced liver toxicity in rats.

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.

Expected adverse health influences due to exposure to glyphosate-based herbicide (GBH) and its environmental outcomes using Wistar rats as experimental animals

A sum of 32 Wistar rats were divided into four equal groups, each containing 8 rats. Study animals were freely subject to normal rodent diet and tap water. One group was put as control. The applied agents were exposed to glyphosate-based herbicide (GBH-400 mg kg–1) GSH (nmol g–1 tissue), (GBH-600 mg kg–1) GSH (nmol g–1 tissue) and (GBH-850 mg kg–1) GSH (nmol g–1 tissue) once per day as oral gavage for 6 weeks. Study results clearly revealed that (GBH) significantly (p≤0.05) decreased the levels of GSH in liver, kidney, and brain tissues, due to many reasons including poor diet, chronic disease, infection and constant stress, besides aging. Biological negative influences of glyphosate herbicide through the scientific community, including government and non-government organizations have increased their interest in detecting and controlling the environmental agents responsible for damages to the human health and sustainability of the ecosystems.

Endotoxin lipopolysaccharide (LPS)-induced peripheral inflammation and its impact on brain and liver function

Endotoxin Lipopolysaccharide (LPS) induces an innate immune response and activates sickness behavior. During neuroinflammation, the activated microglial cells change its morphology and release various chemicals that could be harmful such as nitric oxide (NO), reactive oxygen species (ROS) and enzymes for proteolysis. Through the buildup of free radicals and ROS, these neuroinflammations can also result in oxidative stress. This ROS reacts with cellular macromolecules, triggering a cascade that results in membrane porosity caused by membrane lipid peroxidation (LPO), which is measured by the quantity of malondialdehyde (MDA). On LPS challenge, the complex behaviour that decreased common activities and explorations, is noticed and with rising anxiety, cognitive impairment and decreased social activities. It also decreased closed arm time, although closed arm entries were higher which may be related to the increased locomotion. It raised open arm time and open arm entries, suggesting of reduced anxiety and also increased exploratory behaviour. AChE and nNOS were increased in the forebrain part. Reduction in brainstem and MDA activity decreased on both forebrain and brain stem. MDA in the liver increased by LPS challenge indicating upregulated hepatic tissue damage and oxidative stress. As a result of LPS-induced lipid peroxidation and oxidative stress, brain Glutathione (GSH), a substrate for cytosolic Glutathione peroxidase, increased in the forebrain and decreased in the brainstem. Decreased scavenging of ROS was indicated by the LPS-induced decrease in liver GSH levels.

Protective Effect of Chrysin Against Chlorpyrifos-induced Hepatotoxicity in Rats: Biochemical and Histopathological Approaches in a Sub-chronic Study.

Chrysin (CH) is one of the important natural flavonoids with antioxidant and anti-inflammatory activity. The aim of this study was to assess the protective effects of CH on biochemical indexes and histopathological changes in the liver of male Wistar rats exposed to chlorpyrifos (CPF). We induced sub-chronic toxicity in rats using CPF (10 mg/kg/day, orally) and administrated CH at 12.5, 25, and 50 mg/kg/day for 45 days. In this study, CPF increased liver enzyme activities compared with the control group (p < 0.05), and co-treated CH with CPF reduced them compared with the non-treated CPF group (p < 0.05). A significant reduction in the liver GSH concentration along with a significant elevation in the concentrations of MDA and NO in the CPF group was observed compared with the control group (p < 0.001). However, CH at a dose of 50 mg could reverse them nearly to the control group (p < 0.001). In the CPF, CPF + CH1, and CPF + CH2 groups, a marked (p < 0.05) increase was found in the serum concentration of IL-6 compared with the control animals. No significant changes were found in the IL-6 concentration of the CPF + CH3 compared with the controls. Moreover, the coadministration of CH plus CPF induced histopathological alterations in liver. These results suggest that CH attenuates hepatic enzymes and histopathological alterations induced by CPF via modulating oxidative stress and inflammatory indices in rats.

Protective Effect of Water-Soluble Acacetin Prodrug on APAP-Induced Acute Liver Injury Is Associated with Upregulation of PPARγ and Alleviation of ER Stress.

A water-soluble acacetin prodrug has been synthesized and reported by our group previously. Acetaminophen (APAP) overdose is a leading cause of acute liver injury. We found that subcutaneous injection of acacetin prodrug (5, 10, 20 mg/kg) decreased serum ALT, AST, and ALP, corrected the abnormal MDA and GSH in liver, and improved intrahepatic hemorrhage and destruction of liver structures in APAP (300 mg/kg)-treated mice. Molecular mechanism analysis revealed that the expressions of endoplasmic reticulum (ER) stress markers ATF6, CHOP, and p-PERK, apoptosis-related protein BAX, and cleaved caspase 3 were decreased by acacetin in a dose-dependent manner in vivo and in vitro. Moreover, via the acacetin-upregulated peroxisome-proliferator-activated receptor gamma (PPARγ) of HepG2 cells and liver, the suppressive effect of acacetin on ER stress and apoptosis was abolished by PPARγ inhibitor (GW9662) or PPARγ-siRNA. Molecular docking revealed that acacetin can bind to three active pockets of PPARγ, mainly by hydrogen bond. Our results provide novel evidence that acacetin prodrug exhibits significant protective effect against APAP-induced liver injury by targeting PPARγ, thereby suppressing ER stress and hepatocyte apoptosis. Acacetin prodrug is likely a promising new drug candidate for treating patients with acute liver injury induced by APAP.

Sodium Pentaborate Prevents Acetaminophen-Induced Hepatorenal Injury by Suppressing Oxidative Stress, Lipid Peroxidation, Apoptosis, and Inflammatory Cytokines in Rats.

Acetaminophen (N-acetyl-p-aminophenol, APAP, or paracetamol) is one of the drugs that may be damaging to the kidneys and liver when used in excess. In this context, it is vital to treat these side effects on the liver and kidneys with various antioxidants. Diseases have been treated using herbal and mineral remedies since ancient times. The mineral boron, found in rocks and water, is a crucial ingredient with multiple positive biological effects. The primary objective of this research is to determine whether or not boron has a protective effect against the toxicity generated by APAP in rats. Male Sprague-Dawley rats were pretreated orally with boron-source sodium pentaborate (B50 and B100 mg/kg) for 6 days by gastric gavage in order to counteract the toxicity caused by a single dose of APAP (1g/kg). APAP increased lipid peroxidation as well as serum BUN, creatinine concentrations, and serum activities of AST, ALP, and ALT by consuming GSH in liver and kidney tissues. In addition, the activity of antioxidative enzymes, including SOD, CAT, and GPx, was diminished. Inflammatory indicators such as TNF-α, IL-1β, and IL-33 were elevated in conjunction with APAP toxicity. In kidney and liver tissues, APAP dramatically increased the activity of caspase-3 and triggered apoptosis. Sodium pentaborate therapy on a short-term basis reduced biochemical levels despite these effects of APAP. This study showed that boron protects rats from the harmful effects of APAP by acting as an anti-inflammatory, antioxidant, and anti-apoptotic agent.

Substituting Fish Meal with Tubiechong (Eupolyphaga sinensis) By-Product in the Diets of Largemouth Bass (Micropterus salmoides): Effects on Growth, Meat Quality, and Liver Health.

A feeding trial was conducted to evaluate the effect of replacing 0% (control), 10% (T10), 20% (T20), 30% (T30), and 40% (T40) fish meal with a Tubiechong (Eupolyphaga sinensis) by-product in largemouth bass (Micropterus salmoides). Triplicate groups of 30 fish (5.36 ± 0.01 g) were fed two times daily to apparent satiation for 60 days. The experimental results showed that the Tubiechong by-product could improve the growth performance of largemouth bass by increasing the FBW, WGR, and SGR until the replacement ratio was 40%. The quadratic regression analysis showed that the proportion of the Tubiechong by-product was 20.79% and 20.91%, respectively, when WGR and SGR were the best. Concurrently, the meat quality in the replacement groups was higher, specifically, the lightness and white values were higher, and the water loss rates were lower (P < 0.05) than that in the control group. Moreover, the changes of the activities of CAT and GSH in the liver and T-AOC and GSH in serum could reveal the antioxidant capacity improvement of fish by the Tubiechong by-product. In the study, the replacement groups had lower T-CHO and HDL-C in serum (P < 0.05), indicating that the Tubiechong by-product had an active role in improving blood lipid and regulating lipid metabolism. Simultaneously, the replacement groups had a normal structure with central hepatocytes' nuclei and deviated from the center partly, while most of the hepatocytes were swollen in the control group with nuclear degeneration. The results showed that the Tubiechong by-product had a positive effect on the liver health of fish. Conclusively, the present study indicated that the partial dietary replacement of fish meal using the Tubiechong by-product (for up to 40% replacement level) in the diet of largemouth bass not only caused no adverse effects on fish health but also improved the growth performance, meat quality, antioxidant capacity, and hepatic health and is conducive to supplying nutritious, high-quality, and healthy aquatic products.