Acetaminophen-Induced Rat Hepatotoxicity Based on M1/M2-Macrophage Polarization,in Possible Relation to Damage-Associated Molecular Patterns and Autophagy

Overdose of acetaminophen (APAP), an antipyretic drug, is an important cause of liver injury. However, the mechanism in the rat model remains undetermined. We analyzed APAP-induced hepatotoxicity using rats based on M1/M2-macrophage functions in relation to damage-associated molecular patterns (DAMPs) and autophagy. Liver samples from six-week-old rats injected with APAP (1000 mg/kg BW, ip, once) after 15 h fasting were collected at hour 10, and on days 1, 2, 3, and 5. Liver lesions consisting of coagulation necrosis and inflammation were seen in the affected centrilobular area on days 1 and 2, and then, recovered with reparative fibrosis by day 5. Liver exudative enzymes increased transiently on day 1. CD68⁺ M1-macrophages increased significantly on days 1 and 2 with increased mRNAs of M1-related cytokines such as IFN-γ and TNF-α, whereas CD163⁺ M2-macrophages appeared later on days 2 and 3. Macrophages reacting to MHC class II and Iba1 showed M1-type polarization, and CD204⁺ macrophages tended to be polarized toward M2-type. At hour 10, interestingly, HMGB1 (representative DAMPs) and its related signals, TLR-9 and MyD88, as well as LC3B⁺ autophagosomes began to increase. Collectively, the pathogenesis of rat APAP hepatotoxicity, which is the first, detailed report for a rat model, might be influenced by macrophage functions of M1 type for tissue injury/inflammation and M2-type for anti-inflammatory/fibrosis; particularly, M1-type may function in relation to DAMPs and autophagy. Understanding the interplayed mechanisms would provide new insight into hepato-pathogenesis and contribute to the possible development of therapeutic strategies.     

Antioxidant activities of chicken liver hydrolysates by pepsin treatment

This study was divided into two parts: (i) an optimal hydrolysing procedure of chicken liver hydrolysates (CLHs) and (ii) the in vivo antioxidant properties of CLHs via a D‐galactose‐induced mouse model. A pepsin‐to‐raw chicken liver mass ratio (1:400, w:w) and 2‐h hydrolysing period were chosen to manufacture CLHs based on yield, peptide level and antioxidant effect. Molecular masses of CLHs were lower than 10 kDa. CLH was rich in aspartic acid and glutamic acid, and also contained both manganese and selenium, which are essential cofactors of superoxide dismutase and glutathione peroxidase, respectively. The contents of cadmium, mercury, tin, and arsenic in CLHs were very low and even no detectible. Regarding the in vivo antioxidant activity of CLHs, a dosage of 1.2 g D‐galactose kg^?1 body weight increased (P < 0.05) 2‐thiobarbituric acid reactive substances values and decreased (P < 0.05) glutathione and Trolox equivalent antioxidant capacity values, as well as superoxide dismutase, catalase, and glutathione peroxidase activities in serum and organs of mice. However, the in vivo antioxidant capacities were improved (P < 0.05) by supplementing CLHs.     

Neuroprotective Role of Liver Growth Factor “LGF” in an Experimental Model of Cerebellar Ataxia

Cerebellar ataxias (CA) comprise a heterogeneous group of neurodegenerative diseases characterized by a lack of motor coordination. They are caused by disturbances in the cerebellum and its associated circuitries, so the major therapeutic goal is to correct cerebellar dysfunction. Neurotrophic factors enhance the survival and differentiation of selected types of neurons. Liver growth factor (LGF) is a hepatic mitogen that shows biological activity in neuroregenerative therapies. We investigate the potential therapeutic activity of LGF in the 3-acetylpiridine (3-AP) rat model of CA. This model of CA consists in the lesion of the inferior olive-induced by 3-AP (40 mg/kg). Ataxic rats were treated with 5 µg/rat LGF or vehicle during 3 weeks, analyzing: (a) motor coordination by using the rota-rod test; and (b) the immunohistochemical and biochemical evolution of several parameters related with the olivo-cerebellar function. Motor coordination improved in 3-AP-lesioned rats that received LGF treatment. LGF up-regulated NeuN and Bcl-2 protein levels in the brainstem, and increased calbindin expression and the number of neurons receiving calbindin-positive projections in the cerebellum. LGF also reduced extracellular glutamate and GABA concentrations and microglia activation in the cerebellum. In view of these results, we propose LGF as a potential therapeutic agent in cerebellar ataxias.     

Relationship between Non-Alcoholic Fatty Liver Disease and Psoriasis: A Novel Hepato-Dermal Axis?

Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra-hepatic organ systems and interacts with the regulation of several metabolic and immunological pathways. In this review we discuss the rapidly expanding body of clinical and epidemiological evidence supporting a strong association between NAFLD and chronic plaque psoriasis. We also briefly discuss the possible biological mechanisms underlying this association, and discuss treatment options for psoriasis that may influence NAFLD development and progression. Recent observational studies have shown that the prevalence of NAFLD (as diagnosed either by imaging or by histology) is remarkably higher in psoriatic patients (occurring in up to 50% of these patients) than in matched control subjects. Notably, psoriasis is associated with NAFLD even after adjusting for metabolic syndrome traits and other potential confounding factors. Some studies have also suggested that psoriatic patients are more likely to have the more advanced forms of NAFLD than non-psoriatic controls, and that psoriatic patients with NAFLD have more severe psoriasis than those without NAFLD. In conclusion, the published evidence argues for more careful evaluation and surveillance of NAFLD among patients with psoriasis.     

Effect of ultrasonic pretreatment on the antioxidant properties of porcine liver protein hydrolysates

In this study, the effect of ultrasonic pretreatment on the antioxidant activity of porcine liver protein hydrolysates (PLPHs) was investigated. The results showed that the degree of hydrolysis (DH) and peptide contents of the PLPHs increased as the time of ultrasonication increased. The hydrolysate pretreated with ultrasonication for 60 s exhibited the highest DH and peptide contents. The hydrolysate pretreated with ultrasonication for 45 s exhibited the highest ferrous ion chelating ability and reducing power. The hydrolysate pretreated with ultrasonication for 30 s exhibited the highest 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging activity and the higher inhibitory activity in the linoleic acid autoxidation system. The molecular weight of peptides in the hydrolysates was less than 6.2 kDa. The results clearly demonstrated that ultrasonic pretreatment enhances the antioxidant activities of the PLPHs in a short period of time (15–30 s).     

Turkey liver: Physicochemical characteristics and functional properties of protein fractions

Turkey liver is an important edible meat by-product. However, it is generally unprocessed, underutilized and low-priced compared to mammalian livers. The present investigation was conducted to provide information on physicochemical composition and functional characteristics of turkey liver. Proximate composition (%) was: moisture (72.3 ± 1.2), protein (21.9 ± 0.6), fat (2.9 ± 1.6), carbohydrate (1.4 ± 0.7), and total ash (1.5 ± 0.1). Cholesterol, glycogen and total heme pigments (g/kg) in the turkey liver were 2.05 ± 0.06, 5.36 ± 0.01 and 2.3 ± 0.08, respectively. Contents in saturated, monounsaturated and polyunsaturated fatty acids (%) were 42.5, 14.6 and 32.6 respectively. Interestingly, turkey liver fat also contains 5% of camphor (oxygenated monoterpene). Mineral concentrations (mg/kg) in liver were: Na (817 ± 14), K (1390 ± 90), Ca (31.4 ± 0.3), Mg (23 ± 0.4), Fe (161 ± 5), Zn (40 ± 2) and Cu (34 ± 2). Liver proteins extracted at 5 or 10 g/l NaCl showed the highest foaming capacity (P < 0.05). Addition of xanthan (1-3 g/l) to liver proteins improved both foam formation and its stability (P < 0.05). Turkey liver also showed interesting emulsifying properties. The emulsion stability of liver proteins was more pronounced at high NaCl concentration (20 g/l). The highest emulsion stability was obtained at acidic or basic pH values (P < 0.05) and decreased at pH 6.     

肝CT图像中阴影部分的精确检测

肝部阴影是肝癌的重要疑似对象,因此检测肝癌可以先将肝部阴影检测出来.但肝部阴影与正常肝组织密度接近,很难分割.为此,提出一种CV分割方法的初始距离函数的设置方法,该方法使初始曲线一开始就接近图像的分割边缘,极大地减少了CV方法的迭代次数,加快了CV方法目标提取的速度.最后将该方法应用于肝部阴影的精确检测,成功地分割了图像中的肝部组织与其中的阴影部分.     

Inhibitory effects of curcumin on activity of cytochrome P450 2C9 enzyme in human and 2C11 in rat liver microsomes

Cytochrome P450 2C9 (CYP2C9), one of the most important phase I drug metabolizing enzymes, could catalyze the reactions that convert diclofenanc into diclofenac 4′-hydroxylation. Evaluation of the inhibitory effects of compounds on CYP2C9 is clinically important because inhibition of CYP2C9 could result in serious drug–drug interactions. The objective of this work was to investigate the effects of curcumin on CYP2C9 in human and cytochrome P450 2C11 (CYP2C11) in rat liver microsomes. The results showed that curcumin inhibited CYP2C9 activity (10?µmol?L^–1 diclofenac) with half-maximal inhibition or a half-maximal inhibitory concentration (IC50) of 15.25?µmol?L^–1 and Ki?=?4.473?µmol?L^–1 in human liver microsomes. Curcumin’s mode of action on CYP2C9 activity was noncompetitive for the substrate diclofenanc and uncompetitive for the cofactor NADPH. In contrast to its potent inhibition of CYP2C9 in human, diclofenanc had lesser effects on CYP2C11 in rat, with an IC50 ≥100?µmol L^–1. The observations imply that curcumin has the inhibitory effects on CYP2C9 activity in human. These in vitro findings suggest that more attention should be paid to special clinical caution when intake of curcumin combined with other drugs in treatment.