Histological Changes In Liver Research Articles

Anti-toll-like receptor 2 antibody ameliorates hepatic injury, inflammation, fibrosis and steatosis in obesity-related metabolic disorder rats via regulating MAPK and NF-κB pathways

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, which includes a spectrum of histological liver changes. Non-alcoholic steatohepatitis (NASH) is considered to be the progressive subtype of NAFLD, which is characterized by lobular inflammation and cellular ballooning on the basis of steatosis. There is a critical need to develop novel and effective therapeutic approaches for NAFLD/NASH. The activation of toll-like receptor 2 (TLR2) signaling pathway plays a key role in high-fat-related inflammation, triggering the occurrence and development of NASH. Herein, the anti-TLR2 monoclonal antibody (TLR2 mAb) was prepared and investigated for its ability to ameliorate the inflammatory response in vivo and in vitro. The anti-inflammatory role of TLR2 mAb in vitro was examined in NR8383 macrophage cells and THP-1 derived macrophage cells. For confirmation in vivo, three groups of SD rats were treated for 20 weeks: rats in the control were fed with a standard diet; rates in the IgG and TLR2 mAb groups were fed with a high-fat diet and with IgG or TLR2 mAb, respectively. Liver tissue and serum were collected for further analysis. Results showed that after 4-week treatment with TLR2 mAb, metabolic parameters in rats were improved markedly (body weight, fasting blood glucose level, liver steatosis, inflammatory response and fibrosis). Moreover, western blotting demonstrated that the TLR2 mAb blocked MAPKs and NF-κB activation, and inhibited the expression of inflammatory factors in rat liver tissue. These effects suggested that TLR2 mAb could improve HFD-induced hepatic injury, inflammation, fibrosis and steatosis by suppressing inflammatory response and regulating the hepatic MAPKs and NF-κB signaling pathways. This suggests that TLR2 may be a novel therapeutic target for metabolic diseases especially NASH.

Protective Effect of Curcumin on Acrylamide-Induced Hepatic and Renal Impairment in Rats: Involvement of CYP2E1

As a chemical extensively used in industrial areas and formed during heating of carbohydrate-rich foods and tobacco, acrylamide (ACR) has been demonstrated to exert a variety of systemic toxic effects including hepatotoxicity and nephrotoxicity. In the present study, we investigated the effect of curcumin, a natural polyphenolic compound in a popular spice known as turmeric, on the hepatic and renal impairment caused by ACR exposure to 40 mg/kg for 4 weeks in rats. The administration of curcumin at doses of 50 and 100 mg/kg to ACR-intoxicated rats significantly decreased the serum levels of alanine transaminase, aspartate transaminase, creatinine, and urea; improved the histological changes of liver and kidney caused by ACR; reduced the number of apoptotic cells; as well as relieved ACR-induced hepatic and renal oxidative stress. Moreover, curcumin inhibited the CYP2E1 overexpression induced by ACR in the liver and kidney tissues. Therefore, curcumin could be applied as a potential strategy for the intervention of ACR-induced systemic toxicity. The inhibition of CYP2E1 might be involved in the protection of curcumin against ACR-induced hepatotoxicity and nephrotoxicity.

Adaptation of Mitochondrial Substrate Flux in a Mouse Model of Nonalcoholic Fatty Liver Disease.

Maladaptation of mitochondrial oxidative flux seems to be a considerable feature of nonalcoholic fatty liver disease (NAFLD). The aim of this work was to induce NAFLD in mice fed a Western-style diet (WD) and to evaluate liver mitochondrial functions. Experiments were performed on male C57BL/6J mice fed with a control diet or a WD for 24 weeks. Histological changes in liver and adipose tissue as well as hepatic expression of fibrotic and inflammatory genes and proteins were evaluated. The mitochondrial respiration was assessed by high-resolution respirometry. Oxidative stress was evaluated by measuring lipoperoxidation, glutathione, and reactive oxygen species level. Feeding mice a WD induced adipose tissue inflammation and massive liver steatosis accompanied by mild inflammation and fibrosis. We found decreased succinate-activated mitochondrial respiration and decreased succinate dehydrogenase (SDH) activity in the mice fed a WD. The oxidative flux with other substrates was not affected. We observed increased ketogenic capacity, but no impact on the capacity for fatty acid oxidation. We did not confirm the presence of oxidative stress. Mitochondria in this stage of the disease are adapted to increased substrate flux. However, inhibition of SDH can lead to the accumulation of succinate, an important signaling molecule associated with inflammation, fibrosis, and carcinogenesis.

Protective effects of prebiotic (resistant maltodextrin) and silymarin against toxicity of carbon tetrachloride in liver rat and kidney

Exposure to carbon tetrachloride induces acute and chronic hepatic injuries as well as renal injuries in rats. Therefore, the current study aimed to evaluate the protective role of prebiotic (digestion resistant maltodextrin) and silymarin against carbon tetrachloride -induced heptorenal toxicity in albino rats. Six groups with ten rats each were used for this purpose; these groups included the control vehicle group that received saline daily for 30 days, prebiotic group (1g/kg, orally) daily for 30 days; silymarin group (200 mg/kg orally) daily for 30 days; carbon tetrachloride group (2.5ml/kg intraperitoneally twice per week for three week; the prebiotic – carbon tetrachloride group; the silymarin – carbon tetrachloride group. The results revealed that carbon tetrachloride significantly increased serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin cholesterol, triglyceride, urea and creatinine. In addition, there were substantial increase in lipid peroxidation (malondialdehyde) and level of glucose with significant decreases in albumin, total protein, creatinine kinase, hemoglobin and red blood cells. Carbon tetrachloride also caused histological changes in liver and kidney tissues. However, administration of prebiotic and silymarin alone ameliorated the carbon tetrachloride induced liver and kidney damage with improved hematological, lipid profile and glucose level. Â

Development, diagnosis and therapy of ketosis in non-gravid and non-lactating Guinea pigs

BackgroundKetosis is a metabolic disorder often triggered by anorexia in animals fed on high energy diets. Although mostly described in pregnant female guinea pigs, under the name of pregnancy toxicosis; there is limited information on ketosis in males and non-pregnant females, often presented to clinics with anorexia or inappetence. The objective of this study was to observe progression of ketosis in guinea pigs, document the changes and evaluate diagnostic methods and a therapeutic approach.ResultsTwenty eight adult guinea pigs (Cavia porcellus), castrated males and intact females of obese and slim body condition were fasted for 3 days and refed afterwards. The slim animals served as control group for body condition. Either slim and fat animals were divided into two treatment groups: half of them received fluid replacements with glucose subcutaneously, the other half did not receive any injection and served as treatment control. Serum beta-hydroxybutyrate, and urine acetoacetate and acetone were measured during and after fasting. Serum ALT, bile acids and liver histology were also analyzed after 7 days of refeeding (and therapy). Females and obese guinea pigs showed a significantly higher increase in ketone bodies in serum and urine. Obese, female, or animals not receiving therapy needed more time to regulate ketone bodies to normal levels than slim animals, males or animals receiving therapy. Liver histology revealed increased hepatocyte degeneration and higher glycogen content in obese animals and animals receiving therapy, and additionally more glycogen content in males. Only minor hepatic fat accumulation was documented. Bile acids showed good correlation to histological liver changes whereas ALT did not.ConclusionsFemale and obese animals react more intensively to fasting. As preventive management, animals should be kept in adequate body condition, fasting should be avoided, and anorexia should be treated immediately. In such a case, urinary dip sticks to detect ketone bodies are a useful diagnostic tool. Glucose therapy leads to faster cessation of ketogenesis and should be recommended in cases of ketosis. However, it needs to be adjusted to avoid hepatocyte glycogen overload and degeneration. Measuring bile acids presents a valuable indicator of liver damage.

Bile duct ligation of C57BL/6 mice as a model of hepatic encephalopathy.

BackgroundBile duct ligation (BDL) has been used for experimental research on hepatic encephalopathy (HE) caused by chronic liver disease. However, little research has been done on a BDL model in C57BL/6 mouse. Therefore, we evaluated the suitability of a BDL model in C57BL/6 mouse for the study of HE and determined which behavioral tests are appropriate for the identification of HE in this model.MethodsTwelve to fourteen-week-old male C57BL/6 mice were randomly assigned to either sham group or BDL group. Histological changes in liver were confirmed by hematoxylin/eosin and Masson’s trichrome staining. Liver function alterations were detected by alanine aminotransferase (ALT) and ammonia levels. To identify behavioral changes, open field, elevated plus maze, novel object recognition, and passive avoidance tests were performed.ResultsInflammatory liver injury and fibrosis were observed 14 days after BDL. ALT and ammonia levels were significantly higher in BDL group than in sham group. There were no differences in general locomotor activity or anxiety between the groups. No difference was observed between these two groups in the novel object recognition test, but BDL group showed significant learning/memory impairment in the passive avoidance test compared to sham group.ConclusionsFourteen days of BDL in 12–14-week-old male C57BL/6 mice is a clinically relevant model for HE, as these mice have liver fibrosis with impaired liver function, hyperammonemia, and learning/memory impairment. Passive avoidance can be used as the major behavioral test in this model of HE.

Zingerone Ameliorates Hepatotoxicity

In medical sciences, toxicity is an area wherein extensive studies have been carried to improve the diseases as well as to prevent. So, there is a high requirement for novel and improved alternative therapeutic strategies to manage diseases. The liver is the largest gland in the body, which executes several important mechanisms; it stores minerals and vitamins and releases them in periods of need. The main aim of this study was to give a closer insight into potent non- toxic compounds that is capable of modifying the responses. Animals were divided into five equal groups viz control (Group 1), administered with food and water ad libitum, (Group 2) administered with olive oil, (Group 3) administered with zingerone, (Group 4) administered with concanavalin A, (Group 5) administered with cyclosporine A followed by zingerone. Our results revealed significant changes in liver marker enzymes and liver histology of zingerone treated rats when compared to control rats. A corollary, zingerone has no toxic effect on hepatocytes and was found to be safe at a dose of 10mg/kg b wt and also ameliorates hepatotoxicity.

Histological Changes in Liver and Kidney of Clarias gariepinus (Burchell, 1822) Juvenile Exposed to Sub-lethal Doses of Chloramphenicol (CAP)

Histological Changes in Liver and Kidney of Clarias gariepinus (Burchell, 1822) Juvenile Exposed to Sub-lethal Doses of Chloramphenicol (CAP)

Protective role of poplar propolis against alcohol-induced biochemical and histological changes in liver and testes tissues of rats

Protective role of poplar propolis against alcohol-induced biochemical and histological changes in liver and testes tissues of rats

The effects of Elateriospermum tapos against obese maternal rat in mitigating obesity development among their adult female offspring

Background: Maternal obesity is a metabolic disorder described by chronic inflammation and dyslipidemia and influences non-communicable diseases in offspring. Elateriospermum tapos is a plant containing high alpha-linolenic acid with antiobesity effect. Objectives: This study was aim to investigate the effect of E. tapos supplementation in obese rat prior pregnancy on the female offspring's body weight, liver and kidney profile, and histological changes of heart, liver, kidney, and retroperitoneal white adipose tissue (RpWAT). Materials and Methods: Thirty female Sprague Dawley rats were used in this study. Six rats were assigned to dams normal diet group fed with standard chow diet. The remaining rats were fed with high-fat and cafeteria diet (HFCD) to generate obesity for 5 weeks. The obese rats were further divided into 4 groups; group1; Dams Negative Control (DNC, normal saline only), group 2; Dams Positive Control (DPC, Orlistat drug 200mg/kg), Dams Treatment 1 (DTX1, E. tapos seed 200 mg/kg) and Dams Treatment 2 (DTX2, E. tapos shell 200mg/kg) extracts for 6 weeks daily prior to mating. The weaning offspring were then designated into 6 groups according to their dam's group (n = 6/group). The offspring were culled at 12th week of age in order to have their blood sample and organs. Results: Adult offspring from DTX2 group showed a decrease in weight gain, alanine aminotransferase, and creatinine level compared to adult offspring from DNC. Histological examination showed that liver and RpWAT of offspring from DTX1 and DTX2 groups were comparable with normal diet group, indicating that the extracts were capable in reversing the high fat diet effect to the organ. Conclusion: E. tapos shell supplementation was effective in reducing the development of obesity with no harmful effect among adult female rat offspring.

Effect of new livestock feeds' phytonutrients on productivity, carcass composition and meat quality in pigs.

Abstract Improving pig growth performance, nutrient digestibility and pork quality is a continual goal of the pig breeding. For this reason, an increasing interest in using phytonutrients has been observed recently. The objective of this study was to determine the impact of Larix sibirica dihydroquercetin or dry distilled Rosa damascena petals on growth performance, carcass composition, meat quality, blood characteristics and histological changes in ovaries and liver in native Danube White fattening pigs. A total of 120 pigs were used in the experiment with duration of 45 days prior to harvest. The pigs were divided into five groups. The control group (C) was fed basal diet. The other four experimental groups were fed with the same diets containing either 3.5 or 7.5 mg dihydroquercetin/kg/d and 0.255 or 0.545 g dry distilled rose petals/kg/d. The supplementations with dihydroquercetin or dry distilled rose petals increased average body weight by 7.74-9.05%, average daily gain by 27.06-30.13%, and feed to gain ratio by 12.53-15.99% and decreased feed consumption by 5.24-13.84% and average liver weight by 10.53-21.12% compared to the control group. Two supplementations didn't cause pathological changes in histological structure of pigs' liver and ovaries, and didn't influence pH values and proximate composition of m. Longissimus thoracis and m. Semimebranosus . No pH determined stress-induced muscle damage was found and the pork carcasses were classified in classes E and U. The two used supplements reduced the blood LDL cholesterol by 13.27-14.29% as well as increased erythrocytes, platelets, haematocrit, mean red blood cell count, mean haemoglobin concentration in erythrocytes, triglycerides and total cholesterol.

Immunohistochemical Analysis of P-gp, LC3-II, and Cathepsin-D Associated with Histological Changes in Fish Liver: from the Impacted Environment to Clean Water

Abstract Herein we evaluated the histopathological alterations and expression patterns of multixenobiotic resistence (MXR) and autophagic proteins in liver samples of fish chronically exposed to anthropogenic contaminants in a highly polluted river, and then again after they had been transferred to good quality water. Two groups were established: euthanized on the day of capture (0 h), and maintained for 30 days in a tank (30 d). The fish of 0 h presented liver with vacuolated and hypertrophic hepatocytes. Also, it was observed strong immunostaining of cathepsin-D, LC3-II and P-gp. Necrosis and apoptosis were also observed throughout the liver. Conversely, the second group (30 d) showed recovery of the liver normal histology and weak immunoreaction of the studied proteins. So, our results indicated that there was a hepatic recovery in the fish kept in good quality water, as showed by the decreased expression of cathepsin-D, LC3-II, and the MXR (P-gp). Therefore, the alterations here observed could be proposed as potential biomarkers to be tested for following the impacts of remediation or mitigation measures to environmental impacts.

Chitosan from crustacean shell waste and its protective role against lead toxicity in Oreochromis mossambicus

In the current study heavy metal removing capability and antioxidant properties of chitosan supplemented diet tested in lead poisoning induced Oreochromis mossambicus in comparison with and standard fish diet. O. mossambicus fishes weighed (20 ± 2gm) were purchased from a local commercial fish pond and acclimated to the laboratory conditions for 10 days. After that fish were dived into four groups, each group received respective feed throughout the experimental period. The fish fed with standard diet exhibited drastic weakening of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GR), glutathione peroxidase (GPx), ascorbic acid, α- tocopherol and β-carotene and also displayed abnormal histological changes in gills, liver, and intestine. The fish fed with a chitosan supplemented diet for 10 days showed substantial enhancements in antioxidant levels and also normal histological structures of organs in the fish.

Effect of Nauclea subdita (Korth.) Steud. leaf extract on hematological and histopathological changes in liver and kidney of striped catfish infected by Aeromonas hydrophila.

Aim:The present study was conducted to investigate the efficacy of different doses of Bangkal (Nauclea subdita) leaf extract on hematological and histological changes in kidney and liver of catfish (Pangasius hypophthalmus) infected by Aeromonas hydrophila.Materials and Methods:Catfish were experimentally infected with A. hydrophila at a dose of 108 cells/mL through intraperitoneal injection, and the hematological and histological changes in the kidney and liver of catfish against the pathogen were observed.Results:Not all concentrations of N. subdita caused a toxic effect in striped catfish. The clinical symptoms of catfish after infection with A. hydrophila and treatment with N. subdita leaf extract included morphological and behavioral changes. N. subdita leaf extract reduced mortality caused by A. hydrophila. Treatment with N. subdita leaf extract was effective in reducing the inflammation by decreasing the activity of neutrophils, monocytes, and lymphocytes. The Hb and Ht levels of catfish significantly decreased after exposure to 108 cells/mL of A. hydrophila and increased significantly after N. subdita treatment. Necrosis percentages in the kidney and liver also decrease after N. subdita treatment.Conclusion:The results indicate that N. subdita leaf extract stimulates the immunity and increases the resistance of catfish to A. hydrophila. N. subdita leaf extract may be used as a potential source for future drug development and food applications.

PHYSIOLOGICAL AND HISTOPATHOLOGCAL STUDY FOR THE EFFECT OF BARLEY (HORDEUN VULGARE) FLOUR ON INDUCED DIABETIC

The aim of this study is to evaluate the effect of barley consumption on sugar reduction in diabetic patients in male and female rats. The mice were divided into six groups with 10 mice per group. The mice injected the substance with 200 mg / kg body weight to induce diabetes. The study included 60 mice of both sexes, injected with aloxane and a dose of 200 mg / kg body weight to induce diabetes. The first group was represented by the control group as its members took standard food from the experimental animal food. The second group, which represents the induced control group as its members took the general measure of food, but injected the substance of the aloxane for comparison. While the third and fourth groups were fed an equal mixture of wheat flour and barley in the form of dry paste for both females and males for mice, respectively. The fifth and sixth groups were fed barley flour only for both sexes. Measure both body weight and blood sugar at the beginning and end of the two weeks of the experiment, where it was fed daily with various food treatments mentioned previously. Different blood parameters were measured, The physiological and histological changes of liver, kidney and brain were also studied. The results showed that there was a significant decrease in the percentage of blood clocates in groups with diabetes, and showed groups treated with barley decreased cholesterol and triglyceride with the emergence of changes in the tissue in the liver and kidneys, while the brain appeared in its natural form. Barley has a protective effect against diabetes.

Genipin Ameliorates Carbon Tetrachloride-Induced Liver Injury in Mice via the Concomitant Inhibition of Inflammation and Induction of Autophagy.

Genipin, as the most effective ingredient of various traditional medications, encompasses antioxidative, anti-inflammatory, and antibacterial capacities. More recently, it is suggested that genipin protects against septic liver damage by restoring autophagy. The purpose of the current study was to explore the protective effect of genipin against carbon tetrachloride- (CCl4-) induced acute liver injury (ALI) and its underlying molecular machinery. Our results indicated that treatment with genipin significantly reduced CCl4-induced hepatotoxicity by ameliorating histological liver changes, decreasing the aspartate aminotransferase and alanine transaminase levels, alleviating the secretion of inflammatory cytokines, and promoting autophagic flux. Moreover, genipin effectively induced the conversion of LC3 and inhibition of p62 accumulation. The liver expressions of ATG5, ATG7, and ATG12 were significantly increased by genipin pretreatment in the ALI mice model. This protective effect may be mediated by the inhibition of mTOR and the activation of p38 MAPK signaling pathways. Meanwhile, genipin attenuated CCl4-induced inflammatory response by inhibiting the NF-κB and STAT3 signaling pathway. In addition, pretreatment with autophagy inhibitor 3-methyladenine (3-MA) or inhibition of p38 MAPK by SB203580 abolished the hepatoprotective effect of genipin. Taken together, our study implicates that genipin has a protective potential against CCl4-induced hepatotoxicity, which might be strongly associated with the induction of autophagy and the attenuation of inflammatory response.

Effects of Belapectin, an Inhibitor of Galectin-3, in Patients With Nonalcoholic Steatohepatitis With Cirrhosis and Portal Hypertension

Increased levels of galectin 3 have been associated with nonalcoholic steatohepatitis (NASH) and contribute to toxin-induced liver fibrosis in mice. GR-MD-02 (belapectin) is an inhibitor of galectin 3 that reduces liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies. We performed a phase 2b,randomized trial of the safety and efficacy of GR-MD-02 in patients with NASH, cirrhosis, and portal hypertension. Patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient [HVPG] ≥ 6 mm Hg) from 36 centers were randomly assigned, in a double-blind manner, to groups that received biweekly infusions of belapectin 2 mg/kg (n= 54), 8 mg/kg (n= 54), or placebo (n= 54) for 52 weeks. The primary endpoint was change in HVPG (Δ HVPG) at the end of the 52-week period compared with baseline. Secondary endpoints included changes in liver histology and development of liver-related outcomes. We found no significant difference in ΔHVPG between the 2 mg/kg belapectin group and placebo group (-0.28 mm HG vs 0.10 mm HG, P= 1.0) or between the 8 mg/kg belapectin and placebo group (-0.25 mm HG vs 0.10 mm HG, P= 1.0). Belapectin had no significant effect on fibrosis or nonalcoholic fatty liver disease activity score, and liver-related outcomes did not differ significantly among groups. In an analysis of a subgroup of patients without esophageal varices at baseline (n= 81), 2 mg/kg belapectin was associated with a reduction in HVPG at 52 weeks compared with baseline (P= .02) and reduced development of new varices (P= .03). Belapectin (2 mg/kg) was well tolerated and produced no safety signals. In a phase 2b study of 162 patients with NASH, cirrhosis, and portal hypertension, 1 year of biweekly infusion of belapectin was safe but not associated with significant reduction in HVPG or fibrosis compared with placebo. However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce HVPG and development of varices. ClinicalTrials.gov number: NCT02462967.

Bisphenol A-induced oxidative damage in the hepatic and cardiac tissues of rats: The modulatory role of sesame lignans.

Bisphenol A (BPA) is an environmental pollutant that is widely produced throughout the world. It is primarily used in the manufacture of polycarbonate plastics, epoxy resins, paints and dental materials. BPA has been reported to promote hepatotoxicity and cardiotoxicity. The antioxidant activity of sesame lignans is well established. The current study assessed the protective efficiency of sesame lignans against BPA-induced hepatotoxicity and cardiotoxicity. Rats were divided into 4 groups: A control group, a BPA-treated group, a sesame lignans-treated group and a sesame lignans and BPA-treated group. Rats were orally administered their respective doses daily [30 mg/kg body weight (BW) BPA and/or 20 mg/kg BW sesame lignans] for 6 weeks. Liver function tests were performed using serum of all groups. Lipid profile and antioxidant status were also measured in liver tissue of the studied groups. The results were confirmed by histopathological examination of liver and heart tissues. The oral administration of BPA was revealed to elicit significant decreases in the activities of hepatic glutathione peroxidase, glutathione reductase, superoxide dismutase and glutathione. It also significantly increased levels of malondialdehyde. Furthermore, BPA-treatment resulted in lipid accumulation, elevated activities of alanine aminotransferase, creatine kinase MB and lactate dehydrogenase, and histological changes of liver and heart tissues. However, the co-administration of sesame lignans and BPA attenuated hepatotoxicity, cardiotoxicity and BPA-induced histological changes. The results of the current study indicated that sesame lignans may be helpful in the development of novel natural drugs to treat hepatic and cardiovascular disorders.

Alterations to transcriptomic profile, histopathology, and oxidative stress in liver of pikeperch (Sander lucioperca) under heat stress

Pikeperch (Sander lucioperca) is an economically important cool-water fish. In recent years, its cultivation has become threatened by higher temperatures in summer. We previously investigated the effects of heat stress on pikeperch liver under different temperatures, but the molecular mechanism of the heat-stress response is still unknown. This study applied consistent heat stress (29 °C, 0–48 h) to pikeperch juveniles, and a transcriptomic profile of pikeperch liver under heat stress (29 °C, 0 h) was performed by RNA-Seq. The antioxidant status, changes in liver histology, and antioxidant gene expression at different time points were examined. We identified 403 differentially expressed genes (DEGs), many of which were enriched in KEGG pathways, including protein processing in endoplasmic reticulum (ER), insulin signaling, and immune-related pathways. Among these, the most significant heat-stress-related pathway was protein processing in ER, indicating that this pathway is critical for the heat-stress response. After consistent heat stress at 29 °C, the total antioxidant capacity (T-AOC), the activities of total superoxide dismutase (T-SOD) and catalase (CAT), and the mRNA expression of manganese SOD (Mn-SOD), CAT, and glutathione peroxidase 1 and 7 (GPx1 and GPx7) in the treated groups showed the same trend of first increasing and then decreasing. Levels of malondialdehyde (MDA) content did not show significant differences between samples at 0 h and 3 h, but significantly increased by 6 h, and thereafter decreased. The liver tissue was normal at 0 h (29 °C); however, it suffered histological damage with increased duration of the heat stress. Above all, heat stress at 29 °C seemed to cause oxidative damage and dysfunction in pikeperch liver between 3 h and 48 h. The present results indicate that pikeperch have the capacity to defend against heat stress and maintain relative balance of oxidation-reduction reactions mainly through activating the antioxidant system, protein processing in ER, the insulin-signaling pathway, and immune-related pathways.

Histone deacetylase 6 inhibitor ACY1215 offers a protective effect through the autophagy pathway in acute liver failure

AimThe purpose of the present study was to elucidate the protective effect of histone deacetylase 6 inhibitor ACY1215 on autophagy pathway in acute liver failure (ALF). Main methodsLipopolysaccharide (LPS) and d-galactosamine (D-Gal) were used to induce ALF model in C57BL/6 mice. D-Gal and tumor necrosis factor alpha (TNF-α) were applied in L02 cell. Autophagy inhibitor 3-MA and ACY1215 were conducted to induce 3-MA group, ACY1215 group and ACY1215+3-MA group. ResultsACY1215 improved liver histological and functional changes in ALF mice model, whereas the autophagy inhibitor 3-MA aggravated liver tissue pathological and functional damage in ALF mice model group. The apoptotic levels (including apoptotic index/rate and apoptotic proteins) in ALF mice and L02 cell were ameliorated with treatment ACY1215. 3-MA accentuated the apoptotic levels in ACY1215 group. D-Gal/TNF-α could reduce L02 cell mitochondrial membrane potential (ΔΨm) in control group. ACY1215 increased the ΔΨm in ALF model. 3-MA also further reduced the ΔΨm in ACY1215 group. ACY1215 could induce autophagy in ALF mice and cell model group accompanied with an increase in expression of LC3-II and beclin-1 proteins and down-regulation of p62 protein. Moreover, the expression of LC3-II and beclin1 proteins were greatly reduced and the expression of p62 protein was ascended after intervention with 3-MA in ACY1215 group. SignificanceHistone deacetylase 6 inhibitor ACY1215 could protect acute liver failure mice and L02 cell by inhibiting apoptosis pathway through enhancing autophagy way.