Supplementing rabbit diets with butylated hydroxyanisole affects oxidative stress,growth performance,and meat quality

Butylated hydroxyanisole (BHA) is a synthetic antioxidant analogous of vitamin E. It is used as a preservative to prevent free radical-mediated oxidation in high-fat foods, and this study's objective was to investigate the effects of BHA on oxidative stress and apoptosis in addition to delineating its efficacy as a growth-promoting feed additive. 60 weaned male rabbits (V-line) were randomly divided into four equal groups: BHA0.0 (control), BHA50, BHA100, and BHA150, administered basal diets with 0.0, 50, 100, and 150 mg BHA/kg of feed for 60 days. Animals were examined for growth performance, markers of oxidative stress and apoptosis, and meat characteristics. Compared to the control group, rabbits receiving BHA-supplemented diets exhibited increases in BW and average daily gain (P < 0.01), where BHA50 and BHA100 groups showed increased muscle content of methionine aspartic acid, serine, and glutamine (P < 0.05). These two groups also exhibited elevated catalase and superoxide dismutase activities and diminished malondialdehyde levels in the liver. Butylated hydroxyanisole upregulated fatty acid synthase gene (FASN), especially in BHA100 animals. Bcl-2-associated X/B-cell lymphoma-2 (Bax/Bcl-2) ratio significantly increased in animals receiving higher doses of BHA, and the weight of the liver significantly increased following BHA treatment. Supplementing growing rabbits with lower doses of dietary BHA may promote growth performance and meat quality via maintaining the redox balance. Hence, the 50–100 mg/kg may be recommended as a safe and still effective feed additive as well as an oxidative stress attenuator.     

Serum levels of anti-heat shock protein 27 antibodies in patients with chronic liver disease

Heat shock protein 27 (HSP27), an intracellular molecular chaperone, is involved in the pathogenesis of cancer by promoting both tumor cell proliferation and resistance to therapy. HSP27 is also present in the circulation and circulating HSP27 (sHSP27) can elicit an autoimmune response with production of antibodies. Levels of sHSP27 are enhanced in patients with hepatocellular carcinoma (HCC); it is, however, unknown whether changes in HSP27 antibody levels occur in patients with HCC and can be exploited as a circulating biomarker of HCC. Our aim was to assess the potential association between newly diagnosed HCC and serum anti-HSP27 antibody levels. In this cross-sectional study, anti-HSP27 antibody levels were measured in serum samples from 71 HCC patients, 80 subjects with chronic liver disease, and 38 control subjects by immunoenzymatic assay. Anti-HSP27 antibody levels did not differ significantly among groups. However, in patients with chronic active hepatitis/cirrhosis, anti-HSP27 levels were significantly higher in subjects with a positive history of alcoholism (p = 0.03). Our data do not support the hypothesis that anti-HSP27 antibody levels may help identify patients with HCC among subjects with chronic liver disease. However, our finding that alcohol-related liver disease is associated with higher anti-HSP27 levels is novel and deserves further investigations.     

益生菌对肝硬化患者肠道菌群和肠道屏障功能的影响

目的探讨益生菌对肝硬化患者肠道菌群、肠道屏障功能及肝脏功能的影响,为肝硬化患者的治疗提供参考。方法选取2017年1月至2019年6月我院收治的60例乙肝肝硬化患者为研究对象。入选患者随机分为观察组和对照组,各30例。对照组患者采用常规治疗,观察组患者在此基础上加用地衣芽孢杆菌胶囊进行治疗。两组患者疗程均为1个月。比较两组患者治疗后肠道菌群、肠道屏障功能、免疫功能、细胞因子水平及肝脏功能变化情况。结果治疗后,对照组患者肠道菌群数量与治疗前比较差异无统计学意义(均P>0.05);观察组患者肠道双歧杆菌、乳杆菌、肠球菌、肠杆菌数量显著高于治疗前及对照组,酵母样真菌数量显著低于治疗前及对照组(均P<0.05)。治疗后,两组患者血清DAO、PCT、ET及D-lac水平均显著降低,同时观察组低于对照组(均P<0.05)。治疗后,观察组患者血清CD3⁺细胞、CD4⁺细胞及CD4⁺/CD8⁺水平均显著上升,同时高于对照组(均P<0.05)。治疗后,两组患者血清IL-2水平显著上升,血清IL-6、TNF-α水平均显著下降(均P<0.05)。治疗后,两组患者Child-Pugh评分,血清TBil、ALT、AST水平均显著降低,且观察组低于对照组(均P<0.05)。结论益生菌可有效调节肠道菌群,提高肠道屏障功能,增强细胞免疫力,减轻炎症反应,改善肝功能,具有较好的辅助治疗作用。     

肝硬化合并结核病患者的临床特征

目的分析肝硬化合并结核病患者的临床特征,为该类患者的治疗提供参考。方法回顾性分析2014年9月至2017年7月于浙江大学医学院附属第一医院住院的肝硬化合并结核病患者的相关资料,总结患者的临床特征。结果共收治68例肝硬化合并结核病患者,其中男性50例(73.5%),女性18例(26.5%),平均年龄(59.9±13.7)岁。在所有患者中,肝硬化最常见的原因是HBV感染(46例,67.7%)和酒精(9例,13.2%)。肺结核(43例)、结核性腹膜炎(13例)、结核性胸膜炎(12例)是最常见的结核类型,此外骨关节结核、结核性脑膜炎、结核性心包炎、泌尿系结核、肠结核、淋巴结结核均可见。该类患者常见临床表现为乏力、腹胀,出现发热的患者不足半数,有盗汗表现的更为罕见。结论肝硬化患者并发结核后可使病情复杂化,增加治疗难度。此外部分患者临床表现不典型,需提高警惕,避免漏诊。     

人体肠道微生态与肝脏免疫关系研究进展

人体微生态学是研究微生物与其宿主相互关系的科学,其中肠道微生态对于人体有最直接的作用。肠道微生态是一个被遗忘的"人体新陈代谢器官",具有维持能量稳态等重要的生理作用。肝脏是人类的重要器官,肝脏中四分之三的血液来自于肠道回流血,其中含有肠道中的细菌产物、环境毒素和食物抗原等。因此肝脏与肠道有最直接的关系。人体肠道微生态中的大量微生物不仅参与调控肠道内的免疫应答,还参与调控肝脏等器官的免疫反应,因此肠道微生态与肝脏免疫密不可分。本文就肠道微生态与肝脏免疫的相关性研究作一综述,以期为人体微生态与肝脏免疫的相关研究提供科学依据。     

Alrp,a survival factor that controls the apoptotic process of regenerating liver after partial hepatectomy in rats

Abstract

Augmenter of Liver Regeneration (Alrp) enhances, through unknown mechanism/s, hepatocyte proliferation only when administered to partially hepatectomized (PH) rats. Liver resection, besides stimulating hepatocyte proliferation, induces reactive oxygen species (ROS), triggering apoptosis. To clarify the role of Alrp in the process of liver regeneration, hepatocyte proliferation, apoptosis, ROS-induced parameters and morphological findings of regenerating liver were studied from PH rats Alrp-treated for 72 h after the surgery. The same parameters, evaluated on regenerating liver from albumin-treated PH rats, were used as control. The results demonstrated that Alrp administration induces the anti-apoptotic gene expression, inhibits hepatocyte apoptosis and reduces ROS-induced cell damage. These and similar data from in vitro studies and the presence of ‘Alrp homologous proteins’ in viruses as well as in mammals (i) allow to hypothesize that Alrp activity/ies may not be exclusive for regenerating liver and (ii) suggest the use of Alrp in the treatment of oxidative stress-related diseases.     

ReviewA Review of the Role of Reactive Oxygen and Nitrogen Species in Alcohol-induced Mitochondrial Dysfunction

Our understanding of the mechanisms involved in the development of alcohol-induced liver disease has increased substantially in recent years. Specifically, reactive oxygen and nitrogen species have been identified as key components in initiating and possibly sustaining the pathogenic pathways responsible for the progression from alcohol-induced fatty liver to alcoholic hepatitis and cirrhosis. Ethanol has been demonstrated to increase the production of reactive oxygen and nitrogen species and decrease several antioxidant mechanisms in liver. However, the relative contribution of the proposed sites of ethanol-induced reactive species production within the liver is still not clear. It has been proposed that chronic ethanol-elicited alterations in mitochondria structure and function might result in increased production of reactive species at the level of the mitochondrion in liver from ethanol consumers. This in turn might result in oxidative modification and inactivation of mitochondrial macromolecules, thereby contributing further to mitochondrial dysfunction and a loss in hepatic energy conservation. Moreover, ethanol-related increases in reactive species may shift the balance between pro- and anti-apoptotic factors such that there is activation of the mitochondrial permeability transition, which would lead to increased cell death in the liver after chronic alcohol consumption. This article will examine the critical role of these reactive species in ethanol-induced liver injury with specific emphasis on how chronic ethanol-associated alterations to mitochondria influence the production of reactive oxygen and nitrogen species and how their production may disrupt hepatic energy conservation in the chronic alcohol abuser.     

Inactivation of Rabbit Liver Carbonyl Reductase by Phenylglyoxal and 2,3,4-Trinitrobenzenesulfonate Sodium

The chemical modifications of rabbit liver carbonyl reductase (RLCR) with phenylglyoxal (PGO) and 2,3,4-trinitrobenzenesulfonate sodium (TNBS), which are respective chemical modifiers of arginine and lysine residues, were examined. RLCR was rapidly inactivated by these modifiers. Kinetic data for the inactivation demonstrated that each one of arginine and lysine residues is essential for catalytic activity of the enzyme. Furthermore, based on the protective effects of NADP +, NAD + and their constituents against the inactivation of RLCR by PGO and TNBS, we propose the possibility that the functional arginine and lysine residues are located in the coenzyme-binding domain of RLCR and interact with the 2′-phosphate group of NADPH.     

Use of precision cut human liver slices for studying the metabolism and genotoxic potential of xenobiotics by means of the 32P-postlabelling technique: steps towards method validation using testosterone and 2-aminofluorene

In the present study, a new in vitro model combining the short-term incubation of precision-cut human liver slices with DNA-adduct analysis by the ³²P-postlabelling technique is proposed for investigation of the genotoxic potential of xenobiotics. For method validation, the metabolic turnover of testosterone (TES) and the DNA-adduct inducing potential of 2-aminofluorene (2-AF) were used. Precision-cut human liver slices were prepared from a total of 12 human liver samples which were freshly obtained as parts of resectates from liver surgery. The slices were incubated as submersion cultures with TES and 2-AF for up to 6 h in 12-well tissue culture plates at concentrations of 10-50 and 0.06-28 μM, respectively. Slices recovered from the slicing procedure in the 4 °C cold Krebs-Henseleit buffer as indicated by intracellular potassium concentrations which increased for 2 h and then remained stable until the end of the incubation. TES was extensively metabolized by human liver slices with a similar metabolite pattern as observed in vivo. Almost 90% of the metabolites were conjugates. Major phase-I metabolites were androstendione, 6β-OH-androstendione, 6β-OH-TES, and 15β-OHTES. After incubation with 2-AF, substance related DNA-adducts were detected which increased dose-dependently from 12 to 1146 adducts per 10⁹ nucleotides. The adduct pattern consisted of one major adduct spot, A, representing 80-90% of the total adduct level and up to four minor adduct spots, B-E. In summary, the present data demonstrate that precision-cut liver slices are a valuable alternative in vitro system for DNA-adduct determination to screen chemicals for potential genotoxicity in humans.     

Autometallography and metallothionein immunohistochemistry in hepatocytes of turbot (Scophthalmus maximus L.) after exposure to cadmium and depuration treatment

In this study, autometallography and immunohistochemistry were used to localize and quantify cadmium and metallothionein (MT) levels, respectively, in cellular compartments of turbot liver on exposure to cadmium for 7 days and further depuration treatment for 14 days. Metals weakly bound to proteins (i.e. MTs) in hepatocyte lysosomes were visualized as black silver deposits (BSDs) using a light microscope. With the aid of a newly developed immunohistochemical procedure, MTs were localized and semi-quantified in both the cytosolic and the lysosomal compartments of hepatocytes. The BSD extent in the lysosomes of hepatocytes increased significantly as a result of cadmium exposure. This response was evidenced after 1h. Further, a progressive increase in the volume density of BSDs occurred up to the seventh day. Total MT immunohistochemical levels increased at a lower rate, starting after 1 day of cadmium exposure. BSD extent values recovered after depuration, whilst MT levels remain unchanged. It is possible that the detoxification rate of metals via lysosomes was diminished, whilst MT levels remained unchanged, at least after 14 days of depuration. It can be concluded that autometallography and MT immunohistochemistry are good tools for clarifying metal and metal-MT trafficking routes in hepatocytes, and also that BSD extent and MT immunohistochemical levels in the lysosomes and cytosol of fish hepatocytes can be considered to be useful biomarkers of metal exposure.