Markers Of Hepatic Damage Research Articles

Elevated serum γ-glutamyl transferase is associated with low muscle function in adults independent of muscle mass

ObjectiveElevated serum γ-glutamyl transferase (GGT), a hepatic cholestasis or liver damage marker, has been associated with low lean mass and adiposity. However, whether serum GGT can predict muscle function in adults remains unclear. The aim of this study was to determine whether an elevated serum GGT is associated with low peak weight-corrected jump power (JP) and low handgrip strength (HGS). MethodsThis study included 662 individuals aged ≥50 y in the final cohort (women, 86%; mean age, 64.8 y). The primary outcome was low peak weight-corrected JP defined as <23.8 W/kg and <19W/kg in men and women, respectively, and the secondary outcome was low HGS (<28 kg in men; <18 kg in women). ResultsParticipants with low JP had a higher GGT level, older age, lower HGS, and higher body fat than those without low JP. Serum GGT showed a negative association with JP (adjusted β = –1.16, P = 0.005) and HGS (adjusted β = –0.92, P = 0.018). One log-unit increment in GGT was associated with elevated odds of low JP (adjusted odds ratio [aOR] 2.13, P = 0.002) after adjustment for age, sex, lean mass, and body fat percentage, particularly in individuals without hepatic steatosis (aOR, 2.30) versus those with hepatic steatosis (aOR, 0.80; Pinteraction = 0.020). ConclusionElevated serum GGT was associated with low muscle function in adults independent of age, muscle mass, and adiposity, indicating that serum GGT may play a role as an independent marker of muscle function. <END ABSTRACT>

Preparation and Characterisation of Liposomes of Bergenia Ciliata Extract and Evaluation of their Hepatoprotective Activity

Acute liver damage (ALD) can cause biochemical and pathological changes, which can lead to major complications and even death. The goal of the study was to examine the therapeutic efficacy of liposomes of Bergenia ciliata extract against thioacetamide-induced liver damage in rats. Liposomal batches of B. ciliata extract were prepared by altering the kind and amount of phospholipids and characterized through various physiochemical properties such as laser diffraction, TEM, encapsulation efficiency, stability and in-vitro release studies. In-vivo hepatoprotective studies were performed on TAA-induced acute hepatic damage model. Further, in-silico studies of bergenin against the three hepatic damage markers viz. TGF-β1, TNF-α and interleukin-6 were also performed. Laser diffraction and TEM showed that most stable liposome batch of B. ciliata extract were in the range of 678–1170 nm with encapsulation efficiency of 84.3±3.5. Extract was found to be rapidly dissociated from B. ciliata liposomes in HCl than PBS, according to in-vitro release data. In-vivo data revealed a significant decline in LFT indicators, amelioration of pathological changes and high bergenin bioavailability in the liposomal group. Protective activity of bergenin against ALD targets like TGF-β1, TNF-α and interleukin-6 was anticipated via molecular docking research. As a result, the current findings of the study indicate that B. ciliata liposomes and bergenin have promising ameliorative potential in the management of ALD.

Updated upper limit of normal for serum alanine aminotransferase value in Vietnamese population

BackgroundAlanine aminotransferase (ALT) is a marker of hepatic damage and its range can be affected by viral hepatitis, alcoholic hepatitis and non-alcoholic fatty liver diseases. We aimed to study the...

Higher hepatic advanced glycation end products and liver damage markers are associated with nonalcoholic steatohepatitis

Advanced glycation end products (AGEs) may be associated with nonalcoholic fatty liver disease (NAFLD) from stimulation of oxidative stress, inflammation, and fibrosis. We hypothesized that patients with NAFLD would have a lower concentration of soluble AGEs receptor and higher quantity of serum and liver AGEs and an increase in hepatic smooth muscle actin alpha (α-SMA) and transforming growth factor beta 1 (TGF-β1) compared with a control group. We compared the presence of hepatic and serum AGEs, AGE soluble receptor (sRAGE), and markers associated with hepatic damage between NAFLD patients and controls without disease. Histological characteristics, plasma biochemical parameters, serum AGEs, serum receptor sRAGE, and liver proteins (α-SMA, TGF-β1, AGEs, immunohistochemistry) were assessed in participants aged 18 to 65 years, with NAFLD (simple steatosis [SS]: n = 7; steatohepatitis [NASH]: n = 15) and controls (n = 11). NASH patients presented higher glycated hemoglobin levels (%) (5.7; 5.4-6.3) compared with SS (5.4; 5.2-5.7) and controls (5.4; 5.3-5.5). The NAFLD activity score (NAS) for NASH patients was 4.9 ± 1.3; for SS patients, 2.0 ± 1.0. NASH patients showed higher hepatic AGEs, TGF-β1, and α-SMA compared with SS and control groups. The NAS score indicates that patients with 5 to 8 had higher hepatic AGEs, TGF-β1, and α-SMA compared with a NAS of 1 to 4 and 0. For α-SMA, a NAS of 1 to 4 was higher than NAS 0. No difference was found in serum AGEs and sRAGE between groups. Higher hepatic AGEs, TGF-β1, and α-SMA were observed with increasing disease severity (according to NAS); therefore, endogenous liver AGEs may participate in hepatic damage progression.

FGF4 protects the liver from nonalcoholic fatty liver disease by activating the AMP-activated protein kinase-Caspase 6 signal axis.

NAFLD represents an increasing health problem in association with obesity and diabetes with no effective pharmacotherapies. Growing evidence suggests that several FGFs play important roles in diverse aspects of liver pathophysiology. Here, we report a previously unappreciated role of FGF4 in the liver. Expression of hepatic FGF4 is inversely associated with NAFLD pathological grades in both human patients and mouse models. Loss of hepatic Fgf4 aggravates hepatic steatosis and liver damage resulted from an obesogenic high-fat diet. By contrast, pharmacological administration of recombinant FGF4 mitigates hepatic steatosis, inflammation, liver damage, and fibrogenic markers in mouse livers induced to develop NAFLD and NASH under dietary challenges. Such beneficial effects of FGF4 are mediated predominantly by activating hepatic FGF receptor (FGFR) 4, which activates a downstream Ca2+ -Ca2+ /calmodulin-dependent protein kinase kinase beta-dependent AMP-activated protein kinase (AMPK)-Caspase 6 signal axis, leading to enhanced fatty acid oxidation, reduced hepatocellular apoptosis, and mitigation of liver damage. Our study identifies FGF4 as a stress-responsive regulator of liver pathophysiology that acts through an FGFR4-AMPK-Caspase 6 signal pathway, shedding light on strategies for treating NAFLD and associated liver pathologies.

α-Lipoik asit ve N-asetilsisteinin sıçan karaciğerinde dietilnitrozamin ve yüksek yağlı diyetin neden olduğu oksidatif stres ve preneoplastik lezyonlar üzerine etkisi

Aim: Oxidative stress and inflammation are important for development of nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). High fat diet (HFD) acts as promoter and induces cancer formation by diethylnitrosamine (DEN)-initiated carcinogenesis. DEN+HFD experimental model may be suitable to investigate the relationship between diet, cirrhosis and cancer.&#x0D; Methods: Rats were injected with DEN (50 mg/kg/once a week; i.p.) for 4 weeks. After 15 days, rats received HFD with/without supplementations of α-lipoic acid (ALA; 2 g/kg chow), N-acetylcysteine (NAC; 1% w/v drinking water) and their combination for 12 weeks. &#x0D; Results: DEN+HFD-treatment resulted in increase of serum hepatic damage markers, hepatic oxidative stress parameters (lipid/protein oxidation products) and fibrotic changes. However, no HCC nodule was detected. Hepatic GST-pi and Ki-67 expressions also increased. Accordingly, DEN+HFD-treatment resulted in precancerous lesions and high rate of proliferation in the liver. NAC supplementation decreased hepatic oxidative stress and formation of fibrotic and preneoplastic lesions of DEN+HFD-treated rats. However, ALA supplementation did not have a curative effect on these lesions. No synergistic effect was seen with co-administration of ALA and NAC.&#x0D; Conclusions: According to present results NAC, acting as an antioxidant, has ameliorating effect on DEN+HFD-induced oxidative stress and the formation of preneoplastic lesions in liver.

Hepatoprotective Effects of Indole, a Gut Microbial Metabolite, in Leptin-Deficient Obese Mice.

ABSTRACTBackgroundThe gut microbiota plays a role in the occurrence of nonalcoholic fatty liver disease (NAFLD), notably through the production of bioactive metabolites. Indole, a bacterial metabolite of tryptophan, has been proposed as a pivotal metabolite modulating inflammation, metabolism, and behavior.ObjectivesThe aim of our study was to mimic an upregulation of intestinal bacterial indole production and to evaluate its potential effect in vivo in 2 models of NAFLD.MethodsEight-week-old leptin-deficient male ob/ob compared with control ob/+ mice (experiment 1), and 4–5-wk-old C57BL/6JRj male mice fed a low-fat (LF, 10 kJ%) compared with a high-fat (HF, 60 kJ%) diet (experiment 2), were given plain water or water supplemented with a physiological dose of indole (0.5 mM, n ≥6/group) for 3 wk and 3 d, respectively. The effect of the treatments on the liver, intestine, adipose tissue, brain, and behavior was assessed.ResultsIndole reduced hepatic expression of genes involved in inflammation [C-C motif chemokine ligand 2 (Ccl2), C-X-C motif chemokine ligand 2 (Cxcl2); 3.3- compared with 5.0-fold, and 2.4- compared with 3.3-fold of control ob/+ mice, respectively, P < 0.05], and in macrophage activation [Cd68, integrin subunit α X (Itgax); 2.1- compared with 2.5-fold, and 5.0- compared with 6.4-fold of control ob/+ mice, respectively, P < 0.01] as well as markers of hepatic damage (alaninine aminotransferase; −32%, P < 0.001) regardless of genotype in experiment 1. Indole had no effect on hepatic inflammation in mice fed the LF or HF diet in experiment 2. Indole did not change hepatic lipid content, anxiety-like behavior, or inflammation in the ileum, adipose tissue, and brain in experiment 1.ConclusionsOur results support the efficacy of indole to reduce hepatic damage and associated inflammatory response and macrophage activation in ob/ob mice. These modifications appear to be attributable to direct effects of indole on the liver, rather than through effects on the adipose tissue or intestinal barrier.

Evaluation of Hepatoprotective and Antioxidant Activity of Ethanolic Extract of Artabotrys zeylanicus Stem against Various Hepatotoxins Induced Hepatotoxicity in Albino Wister Rats

The objective of the present study was to investigate the antioxidant and hepatoprotective activity of ethanolic stem extract of Artabotrys zeylanicus against paracetamol (PCT), Ethanol (ETN) and Isoniazid and Rifampicin (IR) induced hepatotoxicity in Albino wister rats.&#x0D; Methodology: The material was dried in shade, they were powdered and extracted with ethanol. Preliminary Phytochemical tests were done. The hepatoprotective activity of the ethanol extract was assessed in Albino wister rats. PCT (3 g/kg), ETN (5 gm/kg) and IR (100 mg/kg) has enhanced the levels of various biochemical markers of hepatic damage like Serum Glutamic Oxaloacetic Trasaminase (SGOT), Serum Glutamic pyruvic transaminase (SGPT), Alkaline phosphatise (ALP), bilirubin. Antioxidant levels were tested in all the Hepatotoxins treated and untreated groups.&#x0D; Results: The various biochemical and Histopathological investigations done were Serum Glutamic Oxaloacetic Trasaminase (SGOT), Serum Glutamic pyruvic transaminase (SGPT), Alkaline phosphatise (ALP), Bilirubin, antioxidant activity by 1,1-diphenyl 2-picryl hydrazyl (DPPH), Nitro Blue Tetrazolium (NBT), Hyderogen peroxide (H2O2), lipid perioxidation, hyderoxil radical and nitric oxide. Treatment of ethanolic extract of stem of A. zeylanicus (100mg/kg, 200mg/kg and 400mg/kg body weight) has brought back the altered levels of biochemical markers to the near normal levels in the dose dependent manner. Ethanolic extract of A. zeylanicus were observed to inhibit oxidant stress with the maximum value of 71% and 62% at the concentration of 100 µg/mL. The crude ethanolic extract of A. zeylanicus had a calculated IC50 value of 62.2 and 63.25 μg/mL, which is nearly similar to the calculated IC50 value of the known antioxidant, ascorbic acid, ie 65.3 μg/mL. While the rats treated with AZ extract (100, 200 and 400 mg/kg) which were shown as reduction/absence of inflammatory cells, vascular congestion, cellular degeneration, necrosis and vacuoles. In contrast, the lower doses (100 mg/kg) of ethanolic extract of AZ stem shown low protection than at higher dose 400 mg/kg.&#x0D; Conclusion: Our findings suggested that A. zeylanicus ethanol stem extract possessed a potent antioxidant and hepatoprotective activity.

Immunological and antioxidant role of curcumin in ameliorating fipronil toxicity in Nile tilapia ( Oreochromis niloticus )

This study was carried out to investigate the ameliorating effect of dietary curcumin Curcuma longa (CUR) against the subacute toxicity of fipronil (FIP) on Oreochromis niloticus. One hundred and eighty fish were divided into six groups and kept for 30 days; the first group was kept as a control group fed on commercial diet, while the second and third groups were fed on commercial diets supplemented with 1% (CUR1) and 3% (CUR3) curcumin powder/kg diet respectively. The fourth (FIP), fifth (FIP1) and sixth (FIP3) experimental groups were intoxicated with FIP (1/10 96 h LC50), where (FIP1) and (FIP3) groups were fed on a commercial diet supplemented with 1% and 3% of curcumin powder respectively. Hepatorenal damage markers, immunological, tissue antioxidant parameters and anterior kidney expression of IL-8, IL-1β and TGF-β1 genes were determined. Curcumin alleviated the deteriorative effects of FIP intoxication through decreasing hepatic and renal damage markers, improving serum respiratory burst and lysozyme activities. Curcumin provoked a marked decrease in hepatic and renal malondialdehyde and nitric oxide concentration with a significant improvement in tissues' antioxidant status in FIP-intoxicated fish. Gene expression analysis revealed a significant down-expression of pro-inflammatory markers genes after supplementation of curcumin in FIP-intoxicated fish. In conclusion, the use of 3% curcumin as a feed additive could be implemented to protect fish against the toxic effects of agrochemical wastes via restoring antioxidant and immunological parameters of intoxicated fish.

White adipose tissue-infiltrated CD11b+ myeloid cells are a source of S100A4, a new potential marker of hepatic damage

The endocrine and immunological properties of subcutaneous vs visceral adipose tissue (sWAT and vWAT, respectively) have turned a milestone in the study of metabolic diseases. The cytokine S100A4 is increased in obesity and has a role in adipose tissue dysfunction. However, the cellular source and its potential role in hepatic damage in obesity has not been elucidated. We aim to study the regulation of S100A4 in immune cells present in sWAT and vWAT, as well as its potential role as a circulating marker of hepatic inflammation and steatosis. A cohort of 60 patients with obesity and distinct metabolic status was analyzed. CD11b+ myeloid cells and T cells were isolated from sWAT and vWAT by magnetic-activating cell sorting, and RNA was obtained. S100A4 gene expression was measured, and correlation analysis with clinical data was performed. Liver biopsies were obtained from 20 patients, and S100A4 circulating levels were measured to check the link with hepatic inflammation and steatosis. S100A4 gene expression was strongly upregulated in sWAT- vs vWAT-infiltrated CD11b+ cells, but this modulation was not observed in T cells. S100A4 mRNA levels from sWAT (and not from vWAT) CD11b+ cells positively correlated with glycemia, triglycerides, TNF-α gene expression and proliferation markers. Finally, circulating S100A4 directly correlated with liver steatosis and hepatic inflammatory markers. Our data suggest that sWAT-infiltrated CD11b+ cells could be a major source of S100A4 in obesity. Moreover, our correlations identify circulating S100A4 as a potential novel biomarker of hepatic damage and steatosis.

Hepatocellular damage and inflammation in various forms of alcoholic liver disease

The aim of the study was to evaluate hepatocellular damage and immune inflammation in various forms of alcoholic liver disease (ALD). 104 patients with ALD were examined: 15 (14.4%) with liver steatosis (LS), 19 (18.3%) with steatohepatitis and 70 (67.3%) with liver cirrhosis (LC); men 50 (48.1%), women 54 (51.9%); age 45.78.4 years. Traditional clinical, laboratory, instrumental studies were performed, the levels of fragments of cytokeratin-18 (FCK-18), cytokines IL-1, TNF-, IL-4, IL-6, IL-8 were determined by ELISA. The control group consisted of 39 healthy individuals: men 20 (51.2%), women 19 (48.7%), age 48.58.3 years. In LS, an increase in the level of FCK-18 was noted with normal aminotransferase activity, the content of TNF-, IL-6, IL-1, IL-8 increased and the level of IL-4 decreased compared to those in healthy individuals. In steatohepatitis, a triple increase in aminotransferases and FCK-18 was observed compared with LS, as well as an increase in the level of inflammatory mediators, to a greater extent IL-6, to a lesser extent IL-8, TNF-, a decrease in IL-4, IL-1 remained at the same level. In LC, there was a further increase in FCK-18, significantly more pronounced than an increase in AST, and the increase in cytokines continued to the same extent, the levels of IL-6 and IL-8, to a lesser extent IL-1 and TNF-, and the level of IL-4. With the progression of ALD from LS to steatohepatitis, hepatic cell damage was carried out by equally pronounced processes of hepatocyte necrosis and apoptosis, with the development of cirrhosis of the liver, parenchyma damage occurred mainly due to hepatocyte apoptosis. The immuno-inflammatory process progressively increased from the stage of LS to LC with IL-6 and IL-8 undergoing the greatest dynamics. FCK-18 can serve as a non-invasive marker of hepatic cell damage, and IL-6 and IL-8 markers of immune inflammation in ALD.

A greener protocol for the synthesis of phosphorochalcogenoates: Antioxidant and free radical scavenging activities.

In this contribution, a metal- and base-free protocol has been developed for the synthesis of phosphorochalcogenoates (Se and Te) by using DMSO as solvent at 50°C. A variety of phosphorochalcogenoates were prepared from diorganyl dichalcogenides and H-phosphonates, leading to the formation of a Chal-P(O) bond, in a rapid procedure with good to excellent yields. A full structural elucidation of products was accessed by 1D and 2D NMR, IR, CGMS, and HRMS analyses, and a stability evaluation of the phosphorochalcogenoates was performed for an effective operational description of this simple and feasible method. Typical 77Se{1H} (δSe=866.0ppm), 125Te{1H} (δTe=422.0ppm) and 31P{1H} (δP=-1.0,-13.0 and-15.0ppm) NMR chemical shifts were imperative to confirm the byproducts, in which this stability study was also important to select some products for pharmacological screening. The phosphorochalcogenoates were screened invitro and exvivo tests for the antioxidant potential and free radical scavenging activity, as well as to investigation toxicity in mice through of the plasma levels of markers of renal and hepatic damage. The pharmacological screening of phosphorochalcogenoates indicated that compounds have antioxidant propriety in different assays and not changes plasma levels of markers of renal and hepatic damage, with excision of 3g compound that increased plasma creatinine levels and decreased plasma urea levels when compared to control group in the blood mice. Thus, these compounds can be promising synthetic antioxidants that provide protection against oxidative diseases.

S0984 Long-Term Efficacy and Safety of Obeticholic Acid in Patients With Primary Biliary Cholangitis: A Demographic Subgroup Analysis of 5-Year Results From the POISE Trial

INTRODUCTION: Primary biliary cholangitis (PBC) is a rare, progressive autoimmune liver disease that leads to fibrosis, cirrhosis, and liver transplantation. PBC primarily affects females, but male patients and those with earlier age at diagnosis are at high risk for disease progression. Obeticholic acid (OCA) is approved as second-line treatment of PBC in patients nonresponsive or intolerant to ursodeoxycholic acid. The efficacy and safety of 12-month OCA treatment in patients with PBC was previously demonstrated in the POISE trial.1 We report the long-term efficacy and safety of OCA for more than 5 years in demographic patient subgroups from the POISE trial. METHODS: POISE was a randomized, double-blind, placebo-controlled, 12-month, phase 3 trial evaluating the efficacy and safety of OCA 5–10 mg or 10 mg vs placebo in patients with PBC. This was followed by a 5-year open-label extension (OLE) study during which all patients received OCA. The current analysis evaluated efficacy and safety outcomes in patient subgroups based on sex (male vs female), median age at study entry (≤55 years vs > 55 years), and median age at diagnosis (≤47.5 years vs > 47.5 years). Assessments included changes from OCA baseline in clinical laboratory tests and adverse events (AEs). Paired t-tests assessed within group comparisons. RESULTS: A total of 193 patients were included in the OLE study (median exposure: 5.4 y). In the OLE analysis, significant decreases in mean alkaline phosphatase (ALP) values were observed from OCA baseline for each subgroup from month 3 through month 72 (Figure 1). Similar trends were observed for other key markers of cholestasis and hepatic damage in each subgroup (Table 1). AEs were consistent with previous OCA studies. Over the course of six years of study conduct, 69%–79% of patients reported a pruritus event. CONCLUSION: These findings provide additional information on OCA safety and efficacy in various demographic patient subgroups. Treatment with OCA resulted in improvements in ALP, ALT, AST, and GGT values in patients with PBC in all demographic subgroups assessed. In the OLE, improvements in ALP were achieved by 3 months after OCA treatment initiation and were sustained after 5 years; these are important findings given the progressive nature of the disease.Figure 1Table 1

Análise do estresse oxidativo em ratos Wistar submetidos a treina-mento intervalado de alta intensidade

Physical exercise is a known factor that can promote oxidative stress and may result in cellular damage if not neutralized by antioxidant mechanisms. The aim of this study was to determine if the level of hepatic oxidative stress resulting from high-intensity interval training (HIIT) is affected by the frequency pattern (consecutive vs. non-consecutive) of the training sessions. Thirty-two Wistar rats were divided equally into four groups: two control groups, (CS1) and (CS2), remained sedentary throughout the experiment, and two test groups, (CT1) and (CT2), and were submitted to HIIT for 12 consecutive and nonconsecutive (12 sessions, 3 times/wk over four weeks) days, respectively. There were no significant differences in markers of oxidative damage measured in hepatic tissue (TBARS) and markers of antioxidant activity (Sulfhydryl, FRAP), as well as markers of hepatic damage (AST and ALT) and antioxidant defense (Uric Acid) measured in plasma of both HIIT groups after training compared to the control groups. The results indicate that both HIIT performed for 12 consecutive and nonconsecutive sessions did not promote hepatic oxidative damage in rats.

HEPATOPROTECTIVE ACTIVITY OF WHOLE FLOWER OF HIBISCUS ROSA-SINENSIS LINN EXTRACTS IN WISTAR RATS

The aim of the present study was to evaluate the hepatoprotective effect of ethanolic and aqueous extracts of Hibiscus rosa-sinensis Linn flowers..Carbon tetrachloride-induced hepatic injury in rats and pentobarbitone induced hypnosis methods were used to evaluate the hepatoprotective activity. Alteration in biochemical parameters of hepatic damage, such as alanine transminase (ALT), aspartate transminase (AST), alkaline phosphatase (ALP), triglycerides (TG), cholesterol, total bilirubin, direct bilirubin and pentobarbitone induced sleeping time were tested in different groups of study. Carbon tetrachloride (1mL/kg i.p.) enhances the level of biochemical markers of hepatic damage and increases the sleeping time in mice. Treatment with ethanolic and aqueous extracts of H. rosa-sinensis flowers (200mg/kg and 400mg/kg) has significantly brought back the altered levels of biochemical markers to near normal levels in a dose dependent manner, as compared to silyamarin (100mg/kg) and control group (1% w/V CMC).The result indicaes that the hepatoprotective activity shown may be due to the presence of flavonoids, mucilage, tannins or alkaloids, which justify its folkloric use.

Lipid-encapsulated siRNA for hepatocyte-directed treatment of advanced liver disease

Lipid-based RNA nanocarriers have been recently accepted as a novel therapeutic option in humans, thus increasing the therapeutic options for patients. Tailored nanomedicines will enable to treat chronic liver disease (CLD) and end-stage liver cancer, disorders with high mortality and few treatment options. Here, we investigated the curative potential of gene therapy of a key molecule in CLD, the c-Jun N-terminal kinase-2 (Jnk2). Delivery to hepatocytes was achieved using a lipid-based clinically employable siRNA formulation that includes a cationic aminolipid to knockdown Jnk2 (named siJnk2). After assessing the therapeutic potential of siJnk2 treatment, non-invasive imaging demonstrated reduced apoptotic cell death and improved hepatocarcinogenesis was evidenced by improved liver parenchyma as well as ameliorated markers of hepatic damage, reduced fibrogenesis in 1-year-old mice. Strikingly, chronic siJnk2 treatment reduced premalignant nodules, indicative of tumor initiation. Furthermore, siJnk2 treatment led to a significant activation of the immune cell compartment. In conclusion, Jnk2 knockdown in hepatocytes ameliorated hepatitis, fibrogenesis, and initiation of hepatocellular carcinoma (HCC), and hence might be a suitable therapeutic option, to define novel molecular targets for precision medicine in CLD.

Dietary Supplementation with Chestnut (Castanea sativa) Reduces Abdominal Adiposity in FVB/n Mice: A Preliminary Study.

The production of chestnut (Castanea sativa Miller) is mostly concentrated in Europe. Chestnut is recognized by its high content of antioxidants and phytosterols. This work aimed to evaluate the effects of dietary chestnut consumption over physiological variables of FVB/n mice. Eighteen FVB/n male 7-month-old mice were randomly divided into three experimental groups (n = 6): 1 (control group) fed a standard diet; 2 fed a diet supplemented with 0.55% (w/w) chestnut; and 3 supplemented with 1.1% (w/w) chestnut. Body weight, water, and food intake were recorded weekly. Following 35 days of supplementation, the mice were sacrificed for the collection of biological samples. Chestnut supplementation at 1.1% reduced abdominal adipose tissue. Lower serum cholesterol was also observed in animals supplemented with chestnut. There were no significant differences concerning the incidence of histological lesions nor in biochemical markers of hepatic damage and oxidative stress. These results suggest that chestnut supplementation may contribute to regulate adipose tissue deposition.

Aging and biomarkers: Transcriptional levels evaluation of Osteopontin/miRNA-181a axis in hepatic tissue of rats in different age ranges.

Osteopontin (OPN), a novel hepatic damage marker, as well as several non-coding RNA seem to be associated with liver aging, a little studied and not yet defined process. The aim of the study was to evaluate the expression variations of OPN and miRNA-181a, the transcriptional profiling of long non coding (lnc) RNA GAS-5/miRNA-222 axis and lncRNA NEAT-1 in liver tissue of rats. In addition, to monitor the senescence process, the telomere shortening and TERT/TERC gene expression were also measured. Three groups of male Wistar rats were studied: A (n=6, young); B (n=13, adult); C (n=10, old). Total RNA, including miRNAs, was extracted from liver and analysed by Real-Time PCR. Ultrasound and biochemical evaluation were performed in all rats as well as the histological analysis. OPN mRNA resulted lower in C with respect to A and B while miRNA-181a expression was significantly increased as a function of age. An increasing of both NEAT-1 and miRNA-222 expression as a function of age in parallel with a decreasing of GAS-5 expression in young and old rats, but not in the adults, was observed. A positive correlation was detected between miRNA-181a and miRNA-222. The hepatic ultrasound analysis revealed areas of hyperechogenicity distributed as a function of age. A significant telomere shortening was measured as a function of age while the two subunits TERT and TERC expressions showed an opposite trend. This work could provide a valid starting point to better understand the physiopathological changes during aging, pinpointing in the OPN/miRNA-181a axis significant predictors of successful aging.

Restoration of liver function in malnourished mice orally administered with Pleurotus ostreatus fruiting bodies extract

Context: Malnutrition is considered worldwide as an important burden because it provokes serious damage in several physiological and metabolic mechanisms, among them the hepatic function. Currently, natural products are being used to reduce the negative impact of some pathological disorders in liver. Pleurotus genus of edible mushrooms has shown a wide spectrum of medicinal effects, but its role in the management of liver complications associated to malnutrition is not clear. Aims: To evaluate the restoration of hepatic function in BALB/c malnourished mice, orally administered with a crude water extract (CW-P) from Pleurotus ostreatus fruiting bodies. Methods: Animals (8-week old female BALB/c mice) were starved for 3 days and then refed with commercial diet supplemented with or without CW-P (100 mg/kg) for 8 days. Serum ALP, GGT and amylase activities, hepatic enzymes (ALT, AST, ALP, LDH, GGT), and liver histological examination were assayed. Results: CW-P (34.3 % proteins, 42.6 % carbohydrates and 3.8 g/ 100 g of phenolics) administered to malnourished mice: (i) increased total serum proteins concentration that was correlated with the stimulation in liver protein anabolism, (ii) alleviated hepatic damage markers such as decrease serum ALP levels as well as, in ALP, GGT y AST activities in liver samples, and (iii) improved liver histological architecture similar to control group with decreased lipid accumulation. Conclusions: CW-P supplementation favored liver restoration in malnourished mice. Nutritional interventions with this mushroom extract may be suggested to prevent liver complications associated to malnutrition.

Role of 7-chloro-4-(phenylselanyl) quinoline as an anti-aging drug fighting oxidative damage in different tissues of aged rats.

This study investigated whether subacute treatment with 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) presented antioxidant action in oxidative stress associated with aging in different rat tissues. We also investigated whether plasma selenium levels were altered by aging, as well as the contribution of 4-PSQ administration to these levels. Aged Wistar male rats (23month old) were intragastrically treated with 4-PSQ (5mg/kg) for seven days. On the 14th day of the experimental protocol, plasma was collected to determine selenium levels and biochemical markers of renal and hepatic damage. Furthermore, liver, kidney, spleen and cerebral cortex were removed to determine thiobarbituric acid reactive species (TBARS), non-protein thiols (NPSH), glutathione S-transferase (GST), catalase (CAT) and δ-aminolevulinate dehydratase (ALA-D). Our results showed that one or more parameters changed markedly in the liver, kidney, spleen and cerebral cortex of aged rats. Moreover, biochemical markers of renal and hepatic damage and selenium levels are changed in the plasma of aged rats. Treatment with 4-PSQ repaired redox homeostasis in tissues of aged rats, as well as plasma biochemical markers of renal and hepatic damage and selenium levels. In conclusion, 4-PSQ presented an antioxidant effect in tissues of aged rats, restoring selenium levels, and contributing to the restoration of the damage caused by aging. Thus, 4-PSQ could be a potential candidate for the management of age-related oxidative damage, acting as an anti-aging drug.