Protective Mechanisms of Juncus effusus and Carbonized Juncus effusus against D-Galactosamine-Induced Acute Liver Injury in Mice.

This study investigated the hepatoprotective effects of Juncus effusus (J. effusus) and Carbonized J. effusus against liver injury caused by D-galactosamine (D-GalN) in mice. J. effusus and Carbonized J. effusus were administered by gavage once daily starting seven days before the D-GalN treatment. The results of the study indicated that J. effusus and Carbonized J. effusus suppressed the D-GalN-induced generation of serum alanine transaminase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) was observed. The values of superoxide dismutase (SOD) exhibited an increase. In addition, J. effusus and Carbonized J. effusus promoted the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NADPH quinone oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1) as well as the mRNA expression of Nrf2, HO-1, NQO-1 and Glutamate cysteine ligase catalytic subunit (GCLC). The compressed Carbonized J. effusus demonstrated the optimum impact. These results suggest that J. effusus and Carbonized J. effusus protect against D-GalN-induced acute liver injury through the activation of the Nrf2 pathway.

BrdU does not induce hepatocellular damage in experimental Wistar rats.

Bromodeoxyuridine (BrdU) is used in studies related to cell proliferation and neurogenesis. The multiple intraperitoneal injections of this molecule could favor liver function profile changes. In this study, we evaluate the systemic and hepatocellular impact of BrdU in male adult Wistar rats in 30 %-partial hepatectomy (PHx) model. The rats received BrdU 50 mg/Kg by intraperitoneal injection at 0.5, 1, 2, 3, 6, 9 and 16 days after 30 %-PH. The rats were distributed into four groups as follows, control, sham, PHx/BrdU(-) and PHx/BrdU(+). On day 16, we evaluated hepatocellular nuclei and analyzed histopathological features by haematoxylin-eosin stain and apoptotic profile was qualified by caspase-3 presence. The systemic effect was evaluated by liver markers such as alanine transferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (AP), bilirubin, total proteins and serum albumin content. The statistical analysis consisted of a student t-test and one-way ANOVA. BrdU did not induce apoptosis or hepatocellular damage in male rats. Multiple administrations of BrdU in male rats did not induce significant decrease body weight, but increased serum ALT and LDH levels were found. Our results show that the BrdU does not produce hepatocellular damage.

Short term deuterium depletion in drinking water reduced tumor induced oxidative stress in mice liver.

The aim of current work was able to show the oxidant effect of cancer cells found in any part of the body on the liver and to investigate the possible protective effect of deuterium-depleted water (DDW) on this oxidant effect by determining of some liver parameters. Ehrlich ascites tumor bearing BALB/c mice were used for this purpose. BALB/c mice were selected randomly and divided into four groups (n = 5 in each group) as control group, tumor group, control+DDW group, tumor+DDW group, fifteen days after tumor cell injection, liver tissue samples were taken for all groups. In the tumor group, liver lipid peroxidation, sialic acid and protein carbonyl levels, xanthine oxidase, myeloperoxidase, catalase, gamma-glutamyl transferase, sorbitol dehydrogenase, glutathione peroxidase and glutathione reductase activities, were significantly higher than those in the control group while glutathione levels and paraoxonase1, sodium potassium ATPase, glutathione-S-transferase, alanine transaminase and aspartate transaminase activities decreased significantly. Compared with the tumor group, the changes in all parameters except sialic acid, catalase, alanine transaminase and aspartate transaminase were reversed in the DDW given tumor groups, while sialic acid and catalase values continued to increase, and alanine transaminase and aspartate transaminase values continued to decrease. In conclusion, the consumption of DDW may be beneficial and protective against excessive oxidative stress in cancer complications.

Effects of carbohydrate and protein supplement strategies on endurance capacity and muscle damage of endurance runners: A double blind, controlled crossover trial.

Background: The purpose of this study is to explore the effect of carbohydrate only or carbohydrate plus protein supplementation on endurance capacity and muscle damage. Methods: Ten recreationally active male runners (VO2max: 53.61 ± 3.86 ml/kg·min) completed run-to-exhaustion test three times with different intakes of intervention drinks. There was a 7-day wash-out period between tests. Each test started with 60 minutes of running at 70% VO2max (phase 1), followed by an endurance capacity test: time-to-exhaustion running at 80% VO2max (phase 2). Participants randomly ingested either 1) 0.4 g/kg BM carbohydrate before phase 1 and before phase 2 (CHO+CHO), 2) 0.4 g/kg BM protein before phase 1 and 0.4 g/kg BM carbohydrate before phase 2 (PRO+CHO), or 3) 0.4 g/kg BM carbohydrate before phase 1 and 0.4 g/kg BM protein before phase 2 (CHO+PRO). All subjects ingested carbohydrate (CHO) 1.2 g/kg BM during phase 1, and blood samples were obtained before, immediately, and 24 h after exercise for measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), and myoglobin (MB). Results: There was no significant difference in time to exhaustion between the three supplement strategies (CHO+CHO: 432 ± 225 s; PRO+CHO: 463 ± 227 s; CHO+PRO: 461 ± 248 s). However, ALT and AST were significantly lower in PRO+CHO than in CHO+CHO 24 h after exercise (ALT: 16.80 ± 6.31 vs. 24.39 ± 2.54 U/L; AST: 24.06 ± 4.77 vs. 31.51 ± 7.53 U/L, p < 0.05). MB was significantly lower in PRO+CHO and CHO+PRO than in CHO+CHO 24 h after exercise (40.7 ± 15.2; 38.1 ± 14.3; 64.3 ± 28.9 ng/mL, respectively, p < 0.05). CK increased less in PRO+CHO compared to CHO+CHO 24 h after exercise (404.22 ± 75.31 VS. 642.33 ± 68.57 U/L, p < 0.05). Conclusion: Carbohydrate and protein supplement strategies can reduce muscle damage caused by endurance exercise, but they do not improve endurance exercise capacity.

The Effects of Combined Vitamin E and C for Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD): A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Antioxidant therapy is a promising treatment option for non-alcoholic fatty liver disease (NAFLD) after failure of lifestyle modification. We aimed to explore the efficacy of combined vitamin E and C therapy compared to no treatment for NAFLD. METHODS: A literature search was performed in Ovid Embase, Ovid Medline, PubMed, Cochrane Library, Scopus, and Web of Science from inception to 28th April 2020. A systematic review and meta-analysis were conducted on randomized controlled trials that assessed vitamin E and C co-treatment in NAFLD. Quality of evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Assessed outcomes were changes in imaging findings, histological features, and serum transaminases. Subgroup analyses that compared adult versus children were further explored. RESULTS: Four studies (n=260) satisfied our eligibility criteria. Vitamin co-treatment  did not improve ultrasonographic liver brightness, histological parameters of hepatocyte injury (steatosis, lobular inflammation, and ballooning), fibrosis grading (standardized mean difference [SMD ]: 0.02, 95% CI: -0.40 to 0.45, I2=13%), serum aspartate transaminase (mean difference [MD]: -0.05, 95% CI: -2.59 to 2.50, I2=0%), and serum alanine transaminase (MD: 2.82, 95% CI: -2.11 to 7.76, I2=57%). Subgroup stratifications illustrated similar findings. CONCLUSION: Vitamin co-treatment may have limited efficacy in NAFLD. However, we have little confidence in our effect estimates due to bias and other major constraints.

Preventive Effect and Mechanism of Anthocyanins from Aronia Melanocarpa Elliot on Hepatic Fibrosis Through TGF-ß/Smad Signaling Pathway.

In order to explore the effect and mechanism of Aornia mealnocarpa Elliot anthocyanins (AMA) at the cellular level on hepatic fibrosis (HF), molecular docking, RT-PCR and Western Blotting were used to explore the molecular mechanism and the effects of different doses AMA on HSC-T6 cells by TGF-ß1 induction. The results showed that the binding energy of anthocyanins on TGF-ß1 (PDB ID: 3KFD) was in the range of -9.5 to 8.6 kcal/mol, with good low energy parameters and binding positions. AMA could effectively inhibit the expressions of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum bilirubin (TSB), and improved the expressions of total protein (TP) and albumin (ALB). RT-PCR and Western bloting results showed that AMA could inhibited the secretion of inflammatory cytokines IL-1, IL-6, TNF-α and COX-2, and inhibit the expression of TGF-ß1, P-Smad2, α-SMA and Collagen I in TGF-ß /Smad signaling pathway. This study revealed the AMA's inhibition effects and mechanism of malignant biological behavior of HSC-T6 cells, in order to provide theoretical basis for the prevention and treatment of HF by Aronia melanocarpa Elliot.

Ameliorative role of Cyanus depressus (M.Bieb.) Soják plant extract against diabetes-associated oxidative-stress-induced liver, kidney, and pancreas damage in rats.

In this original article, we aimed to assess the ameliorative role of Cyanus depressus (CD) plant ethanolic extract treatment of streptozotocin (STZ)-induced liver, kidney, and pancreas damage in rats. The rats were divided into five groups (n = 7): control, CD, Diabetes mellitus (DM), DM + CD, and DM + glibenclamide (Gly). The DM groups were injected with a single dose of 50 mg/kg STZ intraperitoneally (i.p.). While the CD and DM + CD groups received 400 mg/kg/day intragastrically for 21 days, the DM + Gly group received 3 mg/kg/day of Gly intragastrically throughout the experiment. Statistically significance was accepted as p < .05. According to our liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) data, quinic acid, cosmosiin, nicotiflorin, apigenin, and protocatechuic acid were the major compounds, in descending order. Weekly blood glucose, serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and urea, malondialdehyde (MDA) (liver and pancreas), and blood glycosylated hemoglobin % (HbA1c %) were significantly decreased, whereas finally live body weights (LBWs), reduced glutathione (GSH), glutathione S-transferase (GST) and catalase (CAT) (pancreas), and pancreatic islet diameter and area were increased significantly in the CD-treated diabetic group. Moreover, CD administration was found to be effective in the protection of the histology of the liver, kidneys, and pancreatic islets in the STZ-induced rats. Consequently, we concluded that CD administration reduces hyperglycemia, oxidative stress, and histopathology in STZ-induced experimental rats by improving antioxidant defenses. PRACTICAL APPLICATIONS: Today, the prevalence of diabetes is increasing rapidly throughout the world and it causes complications such as kidney damage, blindness, amputations, and cardiovascular diseases. Despite medical technological advances, people's interest in medicinal herbal products is gradually increasing. Biochemical and histopathological findings showed that the use of the plant CD at the determined dose (400 mg/kg/day) in rats with DM by STZ had strong antioxidant and antidiabetic effects. CD may have a drug potential in preventing DM and its complications because of its phytochemical content including some phenolic acids such as quinic acid, cosmosiin, nicotiflorin, apigenin, and protocatechuic acid. Isolation of bioactive compounds from CD and investigation of their therapeutic effects could be planned as further studies.

Anti-inflammatory effect of mesenchymal stem cells on hepatocellular carcinoma in the xenograft mice model.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Sorafenib is the standard treatment used in the advanced stages of HCC. Cell therapy with mesenchymal stem cells (MSCs)-based cell therapy has proven effective in immune regulation and tumour growth inhibition. OBJECTIVES: In this study, we investigated the anti-inflammatory effect of MSCs on HCC xenografts. METHODS: Human HepG2 cell lines were subcutaneously implanted into the flank of 12 nude mice, divided into three groups: the control group, the IV group (intravenous MSCs injection) and the local group (local MSCs injection). Mice were sacrificed 6 weeks after tumour implantation, and tumours were resected entirety. Quantitative real-time polymerase chain reaction (qRT-PCR) measured the gene expression of inflammatory markers, including tumour necrosis factor-α (TNF-α), interleukin (IL)-1α and IL-10. Aspartate transaminase (AST), alanine transaminase (ALT) and urea levels were measured using spectrophotometry to ensure the safety of MSC therapy. RESULTS: Gene expressions for all three inflammatory markers were reduced in both MSCs groups compared to the control group. AST, ALT and urea levels remained in normal ranges. CONCLUSIONS: MSC therapy can reduce inflammation in HCC xenograft mouse models.

Protective effects of methanolic leaf extracts of Monanthotaxis caffra against aflatoxin B1-induced hepatotoxicity in rats.

Aflatoxins are potent hepatotoxic and carcinogenic secondary metabolites produced by toxigenic fungi. The present study investigated the protective effect of methanolic leaf extracts of Monanthotaxis caffra (MLEMC) against aflatoxin B1-induced toxicity in male Sprague-Dawley rats. The rats were randomly divided into 6 groups of 8 animals each. Five groups were administered orally for seven days with three different concentrations of MLEMC (100 mg/kg, 200 mg/kg and 300 mg/kg), curcumin (10 mg/kg) or vehicle (25% propylene glycol). The following day, these groups were administered 1 mg/kg b.w. of aflatoxin B1 (AFB1). The experiment was terminated three days after administration of AFB1. Group 6 represented untreated healthy control. Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatinine and liver histopathology were evaluated. Methanolic leaf extracts of M. caffra decreased the levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and creatinine in the sera of rats as compared with the AFB1 intoxicated group. Co-administration of MLEMC improved the histological characteristics of the hepatocytes in contrast to the AFB1 treated group, which had mild to severe hepatocellular injuries including bile duct proliferation, bile duct hyperplasia, lymphoplasmacytic infiltrate and fibrosis. Extracts of M. caffra were beneficial in mitigating the hepatotoxic effects of AFB1 in rats by reducing the levels of liver enzymes and preventing hepatic injury.

Blood glutamate scavenging as a novel neuroprotective treatment for paraoxon intoxication.

Organophosphate-induced brain damage is an irreversible neuronal injury, likely because there is no pharmacological treatment to prevent or block secondary damage processes. The presence of free glutamate (Glu) in the brain has a substantial role in the propagation and maintenance of organophosphate-induced seizures, thus contributing to the secondary brain damage. This report describes for the first time the ability of blood glutamate scavengers (BGS) oxaloacetic acid in combination with glutamate oxaloacetate transaminase to reduce the neuronal damage in an animal model of paraoxon (PO) intoxication. Our method causes a rapid decrease of blood Glu levels and creates a gradient that leads to the efflux of the excess brain Glu into the blood, thus reducing neurotoxicity. We demonstrated that BGS treatment significantly prevented the peripheral benzodiazepine receptor (PBR) density elevation, after PO exposure. Furthermore, we showed that BGS was able to rescue neurons in the piriform cortex of the treated rats. In conclusion, these results suggest that treatment with BGS has a neuroprotective effect in the PO intoxication. This is the first time that this approach is used in PO intoxication and it may be of high clinical significance for the future treatment of the secondary neurologic damage post organophosphates exposure.

Impact of treatment with praziquantel, silymarin and/or beta-glucan on pathophysiological markers of liver damage and fibrosis in mice infected with Mesocestoides vogae (Cestoda) tetrathyridia.

Mesocestoides vogae tetrathyridia infection in mice causes hepatocyte injury, hepatic granulomatous inflammmation, liver fibrosis and chronic peritonitis manifested with portal hypertension. To reduce the detrimental effect of parasites on the host liver, the effect of the anthelmintic drug praziquantel (PZQ) in combination with natural products silymarin (an antioxidant) and beta-glucan (an immunomodulator) was investigated. The therapeutic effect of drugs was assessed by means of aminotransferase (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) activities, content of albumin, total proteins and hyaluronic acid (HA) in sera of ICR mice infected with M. vogae larvae. Animals were treated with PZQ suspended in oil emulsion (Group 1), PZQ combined with silymarin incorporated into lipid microspheres (LMS) (Group 2), PZQ combined with beta-glucan incorporated into liposomes (LG) (Group 3), PZQ co-administered with LMS and LG (Group 4). Untreated animals (Group 5) served as the control. Treatment of animals started at the early chronic phase of infection (day 14 p.i.) and lasted 10 days; serum samples were collected on days 0, 7, 14, 25, 28, 31, 35 and 45 p.i. ALT and AST activities were significantly (P < 0.05) decreased in Groups 2, 3 and 4. HA content was significantly (P < 0.05 and 0.01) lower in Groups 2 and 4. Albumin levels were decreased in Groups 2 and 4, total protein concentration decreased in Groups 1 and 3 (P < 0.05 and 0.01). These results showed that combined treatment of PZQ with silymarin and/or beta-glucan was able to ameliorate or suppress fibrogenesis in the liver, protect liver cells from oxidative damage and, possibly, stimulate regeneration of the parenchyma.

Attenuation of bacterial lipopolysaccharide-induced hepatotoxicity by betaine or taurine in rats.

The effects of betaine or taurine on hepatotoxicity induced by lipopolysaccharide (LPS) were examined in adult male SD rats. Rats were provided with drinking water containing either 1% betaine or taurine for 2 weeks prior to challenge with LPS (5 mg/kg, iv). Supplementation with betaine or taurine protected the animals from induction of LPS hepatotoxicity as measured by changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities and total bilirubin levels in serum, and hepatic glutathione contents. LPS challenge increased serum TNF-alpha and nitrate/nitrite in rats, which were reduced by betaine or taurine intake. Taurine depletion induced by supply of drinking water containing 3% beta-alanine for 7 days did not enhance the LPS-induced hepatic damage or the decrease in hepatic glutathione level. The results indicate that intake of betaine or taurine attenuates the LPS-induced hepatotoxicity resulting from activation of Kupffer cells.