蜂胶黄酮对卡介苗联合脂多糖诱导小鼠免疫性肝损伤的保护作用

目的 探讨蜂胶黄酮(PF)对卡介苗(BCG)与脂多糖(LPS)诱导小鼠免疫性肝损伤的作用.方法 除正常对照组外,采用BCG和LPS诱导小鼠建立免疫性肝损伤模型,随机分为5组,药物实验组分别用300 ms/ks、150 mg/ks、75 mg/ks的蜂胶黄酮干预后,计算肝指数;检测血清中谷丙转氨酶(ALT)和谷草转氨酶(...     

N-acetylcysteine protects against liver injure induced by carbon tetrachloride via activation of the Nrf2/HO-1 pathway

Chronic liver injury is an important clinical problem which eventually leads to cirrhosis, hepatocellular carcinoma and end-stage liver failure. It is well known that cell damage induced by reactive oxygen species (ROS) is an important mechanism of hepatocyte injure. N-acetylcysteine (NAC), a precursor of glutathione (GSH), is well-known role as the antidote to acetaminophen toxicity in clinic. NAC is now being utilized more widely in the clinical setting for non-acetaminophen (APAP) related causes of liver injure. However, the mechanisms underlying its beneficial effects are poorly defined. Thus, Aim of the present study was to investigate potential hepatic protective role of NAC and to delineate its mechanism of action against carbon tetrachloride (CCl₄)-induced liver injury in models of rat. Our results showed that the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as malondialdehyde (MDA) contents decreased significantly in CCl₄-induced rats with NAC treatment. GSH content and superoxide dismutase (SOD) activities remarkably increased in the NAC groups compared with those in CCl₄-induced group. Treatment with NAC had been shown to an increase in nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA levels. In conclusion, these results suggested that NAC upregulated HO-1 through the activation of Nrf2 pathway and protected rat against CCl₄-induced liver injure. The results of this study provided pharmacological evidence to support the clinical application of NAC.     

Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver

Endotoxemia-induced hepatotoxicity is characterized by disturbed intracellular redox balance, excessive reactive oxygen species (ROS) generation inducing DNA, proteins and membrane lipid damages. In the present study, the protective effects of montelukast (MNT) against Escherichia coli lipopolysaccharides (LPS)-induced oxidative stress were investigated in rat liver. LPS (10 mg/kg, i.p.) was injected and the animals were sacrificed 6 h after LPS challenge. MNT (10 mg/kg) was administered orally for seven successive days before endotoxemia induction. Blood samples were withdrawn for assessing the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and levels of serum total bilirubin, total protein, tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β). Livers were dissected out and used for histological examination or stored for the determination of malondialdehyde (MDA), protein carbonyl content (PCC), reduced glutathione (GSH) levels, enzymatic activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO). Sepsis significantly increased ALT, AST, ALP, LDH, total bilirubin, TNF-α and IL-1β, MPO, MDA and PCC levels and decreased total protein, GSH and enzymatic antioxidants (CAT, SOD and GSH-Px). MNT decreased the markers of liver injury (AST, ALT, ALP, LDH, and total bilirubin), inflammatory biomarkers (TNF-alpha, IL-1β), MDA, PCC and MPO after LPS challenge. In conclusion, MNT abrogates LPS-induced markers of liver injury and suppresses the release of inflammatory and oxidative stress markers via its antioxidant properties and enhancement enzymatic antioxidant activities.     

Protective effects of sesamin on liver fibrosis through antioxidative and anti-inflammatory activities in rats

Abstract

Context: Sesamin (Ses) from Sesamun indicum seeds has potent antioxidants and anti-inflammatory effects.

Objective: This study focused on the antioxidant and anti-inflammatory effects of Ses on Carbon tetrachloride (CCl₄)-induced hepatic fibrosis in experimental rats and the potential mechanism underlying the activation of NF-kB pathway.

Materials and methods: Hepatic fibrosis was induced by interaperitoneally (i.p.) administered with 20% CCl₄ in corn oil (2?mL/kg for 8 weeks) in rats. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were checked. The levels of protein carbonyls and antioxidant enzymes such as superoxide dismutase (SOD) and GSH-Px were determined after Ses administration. H&E and Masson’s trichrome staining for histopathological changes of liver tissues were observed. Western blotting was used to detect expression of IL-6, cyclooxygenase-2 (COX-2), and NF-kB activation. Finally, the levels of hydroxyproline in liver tissues were also determined.

Results: Ses decreased the release of liver enzymes – ALT, AST, and TBIL, reduced protein carbonyls, attenuated the reduction of SOD and GSH-Px activities induced by CCl₄ in the liver tissue. It also significantly reduced the levels IL-6 and COX-2 in the liver caused by CCl₄ by inhibition of NF-kB activation. Histological results indicated that Ses significantly improved the pathological lesions of liver fibrosis.

Conclusions: Ses exerted hepatoprotective effects possibly due to the antioxidant effect and suppressing the NF-kB activation.     

Coenzyme Q10 and Silymarin Reduce CCl4-Induced Oxidative Stress and Liver and Kidney Injury in Ovariectomized Rats—Implications for Protective Therapy in Chronic Liver and Kidney Diseases

Oxidative stress is one of the key factors in the pathophysiology of liver disease. The present study aimed to evaluate the potential impact of two antioxidants, namely coenzyme Q10 (CoQ10) and silymarin, on carbon tetrachloride (CCl₄)-induced oxidative stress and hepatic damage in ovariectomized rats. Female Long Evans rats were divided into six groups (n = 6): control, CCl₄, CCl₄ + CoQ10 (200 mg/kg), CCl₄ + silymarin (140 mg/kg), Control + CoQ10, and Control + silymarin. Plasma and tissues from liver and kidney were analyzed for oxidative stress parameters and antioxidant enzyme activities using biochemical assays. Infiltration of inflammatory cells and fibrosis were assessed by histological staining of tissue sections. Both CoQ10 and silymarin significantly lowered serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels that were detected to be higher in CCl₄ rats compared to controls. Significant reduction in CCl₄-induced elevated levels of oxidative stress markers malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) was observed with both antioxidants. However, in control rats, CoQ10 and silymarin did not produce a significant effect. Histological analysis revealed that CCl₄ markedly increased the level of inflammatory cells infiltration and fibrosis in liver and kidney tissues, but this was significantly reduced in CCl₄ + CoQ10 and CCl₄ + silymarin groups. Taken together, our results suggest that CoQ10 and silymarin can protect the liver against oxidative damage through improved antioxidant enzyme activities and reduced lipid peroxidation. Thus, supplementation of the aforementioned antioxidants may be useful as a therapeutic intervention to protect liver health in chronic liver diseases.     

Effect of Potassium Bromate on the Liver of Adult Male Albino Rat and A Possible Protective Role of Vitamin C: Histological,Immunohistochemical, and Biochemical Study

Potassium bromate (KBrO₃) is a food additive which is used primarily as a maturing agent for flour. It is proved as a toxic agent with significant reduction in the activities of antioxidant capacity. The therapeutic efficacy of vitamin C as antioxidant may provide a possible solution to KBrO₃ mediated oxidative damage. Twenty four adult male albino rats were used to evaluate the protective role of vitamin C against KBrO₃ induced hepatotoxicity and divided into four groups; Group 1 (control), Group 2: received 30 mg/Kg/day vitamin C orally for 4 weeks, Group 3: received 20 mg/Kg/dose KBrO₃ orally twice weekly for 4 weeks and Group 4: received both KBrO₃ and vitamin C. Liver specimens were processed for histological study by light and electron microscopes and stained immunohistochemically to detect glial fibriller acidic protein (GFAP). Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated as well as the levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities in all dissected tissues were determined. KBrO₃ induced histological alterations in the form of degeneration, cellular infiltration and significant increase in collagen deposition in portal tracts with a significant increase in immunoexpression of GFAP. Significant rise in serum levels of AST, ALT, and MDA in liver tissues were recorded. However, levels of GSH and SOD were significantly decreased. Most of these changes were improved by vitamin C treatment. In conclusion, vitamin C ameliorates the histological and biochemical alterations of the liver induced by KBrO₃. Anat Rec, 299:1256–1269, 2016. © 2016 Wiley Periodicals, Inc.     

Danshensu-mediated protective effect against hepatic fibrosis induced by carbon tetrachloride in rats

The culprit of hepatic fibrosis (HF) is linked to suprathreshold deposition of collagen. Thus, collagen reduction by improved metabolism contributes to HF management. In this study, we aimed to investigate the hepatoprotective effects of Danshensu (DSS) against carbon tetrachloride (CCl₄)-induced HF rats. The results showed that DSS-administrated rats resulted in decreasing in hepatosomatic indexes, and lowering serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Meanwhile, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were increased, while the content of malonaldehyde (MDA) was lessened in liver tissue of DSS administration group. In addition, the pro-fibrotic markers of hydroxyproline (Hyp), type III procollagen (PCIII) and hyaluronic acid (HA) contents were decreased. Histopathological examination confirmed that the hepatotoxicity in CCl₄-injured rats was alleviated following the DSS administration. Furthermore, intrahepatic protein expressions of alpha-smooth muscle actin (α-SMA), phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) were effectively down-regulated, respectively. Overall, this work demonstrates that DSS played the protective effect against CCl₄-induced cytotoxicity in liver tissue, which the probable mechanism is associated with attenuation of lipid peroxidation, collagen accumulation and enhancement of anti-oxidative defense capability, as well as regulation of intrahepatic JAK/STAT pathway for maintaining collagenic homoeostasis.     

Hepatoprotective effects of phloretin against CCl4-induced liver injury in mice

This study was designed to characterize the protective capacity of phloretin against acute liver oxidative injury induced by CCl₄ in mice. Administration of phloretin at 100, 200 and 500?mg/kg·bw orally daily in mice for 21 consecutive days, prior to intraperitoneal injection of 0.5% CCl₄/peanut oil (ip, 0.3?mL), significantly reduced the CCl4-induced inhibition of serum alanine aminotransferase, aspartate aminotransferase and lactic dehydrogenase activities. Furthermore, phloretin elevated glutathione and superoxide dismutase activities and reduced formation of malonaldehyde in the liver of mice, when compared with CCl₄-intoxication mice. Moreover, phloretin also prevented the CCl₄-caused liver histological alteration, as indicated by histopathological evaluation. These data collectively demonstrated the potential prospect of phloretin as functional ingredient to prevent liver injury.     

Hepatoprotective Properties of Aqueous Leaf Extract of Persea Americana,Mill (Lauraceae) ‘Avocado’ Against CCL4-Induced Damage in Rats

Background

Natural products from plants have received considerable attention in recent years due to their diverse pharmacological properties, including antioxidants and hepatoprotective activities. The protective effects of aqueous extract of Persea americana (AEPA) against carbon tetrachloride (CCl₄)-induced hepatotoxicity in male albino rats was investigated.

Materials and Methods

Liver damage was induced in rats by administering a 1:1 (v/v) mixture of CCl₄ and olive oil [3 ml/kg, subcutaneously (sc)] after pre-treatment for 7 days with AEPA. Hepatoprotective effects of AEPA was evaluated by estimating the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and levels of total bilirubin (TBL). The effects of AEPA on biomarkers of oxidative damage (lipid peroxidation) and antioxidant enzymes namely, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were measured in liver post mitochondrial fraction.

Results

AEPA and Reducdyn® showed significant (p<0.05) hepatoprotective activity by decreasing the activities of ALT, AST, ALP and reducing the levels of TBL. The activities of antioxidant enzymes, levels of malondialdehyde and protein carbonyls were also decreased dose-dependently in the AEPA-treated rats. Pre-treatment with AEPA also decreased the serum levels of glutathione significantly.

Conclusion

These data revealed that AEPA possesses significant hepatoprotective effects against CCl₄-induced toxicity attributable to its constituent phytochemicals. The mechanism of hepatoprotection seems to be through modulation of antioxidant enzyme system.     

Effects of erdosteine on acetaminophen-induced hepatotoxicity in rats

We investigated the effects of erdosteine on acetaminophen (APAP)-induced hepatotoxicity in rats. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), AST (aspartate aminotransferase), and ALT (alanine transaminase) activities, and malonyldialdehyde (MDA) and nitric oxide levels as oxidant/antioxidant biochemical parameters were investigated with light microscopic evaluation in adult female Wistar Albino rats. APAP administration produced a decrease in hepatic SOD, CAT, and GSH-Px activities, and coadministration of erdosteine (150 and 300 mg/kg) resulted in increases in the activities. MDA and NO levels increased in the APAP group, and erdosteine treatments prevented these increases. Significant elevations in serum AST and ALT levels were observed in the APAP group, and when erdosteine and APAP were coadministered, their serum levels were close to those in the control group. Light microscopic evaluation of livers showed that there were remarkable centrilobular (zone III) hepatic necrosis and mild to moderate sinusoidal congestion in the APAP group, whereas in the erdosteine group, cellular necrosis was minimal and the hepatocytes maintained a better morphology when compared to the APAP group. Erdosteine prevented APAP-induced liver injury and toxic side effects probably through the antioxidant and radical scavenging effects of erdosteine.     

Studies of the protective effect and antioxidant mechanism of blueberry anthocyanins in a CC14-induced liver injury model in mice

This study investigated the protective effects and antioxidant mechanisms of blueberry anthocyanin extract (BBAE) in vivo and in vitro using the model of acute CC1₄-induced liver injury in mice. It was found that BBAE significantly inhibited CC1₄-induced liver injury and inhibited acute ethanol-induced increases in alanine aminotransferase, aspartate aminotransferase and malondialdehyde in a dose-dependent manner (P<0.05). The activities of superoxide dismutase, catalase and glycogen and glutathione reductase were markedly increased in the anthocyanin group (P<0.01). BBAE also significantly suppressed cellular injury and apoptotic cell death. In summary, BBAE possesses marked protective effects against CC1₄-induced liver injury, related to its ability to reduce human embryonic-liver cell (L-02) apoptosis and damage induced by oxidative stress. These findings indicate that BBAE may be of value in protecting against acute liver injury, providing pharmacological evidence supporting its clinical application.     

Hepatoprotective effects of Lycium chinense Miller fruit and its constituent betaine in CCl4-induced hepatic damage in rats

The hepatoprotective activities of Lycium chinense Miller (LC) fruit extract and its component betaine were investigated under carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. The treatment of LC fruit extract significantly suppressed the increase of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the sera of CCl₄ injured rats, and restored the decreased levels of anti-oxidant enzymes such as total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and suppressed the expression of inflammatory mediators including inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-1 and -2. To visualize the potential activity of betaine, a component of LC fruit, betaine was substituted for LC extract in CCl₄ injured rats. The biochemical profile in CCl₄ injured rats co-treated with betaine matched those of LC fruit treated CCl₄ injured rats. The ameliorative effects of LC extract, as well as betaine, were also confirmed by histopathological examination. Collectively, the present findings imply that LC fruit, via its component betaine, mitigate CCl₄-induced hepatic injury by increasing antioxidative activity and decreasing inflammatory mediators including iNOS and COX-1/COX-2.     

Chlorella vulgaris extract ameliorates carbon tetrachloride-induced acute hepatic injury in mice

The possible protective effects of Chlorella vulgaris extract (CVE) on carbon tetrachloride (CCl₄)-induced acute hepatic injury in mice and the mechanism underlying these effects was investigated. CCl₄ administration caused a marked increase in the levels of serum aminotransferases, lipid peroxidation and cytochrome P450-2E1 (CYP450) expression. Also, decreased glutathione (GSH) content and activities of cellular antioxidant defense enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and glutathione-S-transferase (GST) were found after CCl₄ exposure. All of these phenotypes were markedly reversed by preadministration of the mice with CVE. In addition, CVE exhibited antioxidant effects on FeCl₂–ascorbate induced lipid peroxidation in mouse liver homogenates, and on superoxide radical scavenging activity. Taken together, these results suggest that CVE produced a protective action on CCl₄-induced acute hepatic injury in mice, presumably through blocking CYP-mediated CCl₄ bioactivation, inducing the GSH levels, antioxidant enzyme activities and free radical scavenging effect. Therefore, CVE may be an effective hepatoprotective agent and viable candidate for treating hepatic disorders and other oxidative stress-related diseases.     

Hepatoprotective effect of acetonic and methanolic extracts of Heterotheca inuloides against CCl4-induced toxicity in rats

A model of hepatotoxicity by carbon tetrachloride (CCl₄) in rats was used in order to evaluate the protective potential of the acetonic and methanolic extracts of Heterotheca inuloides. Pretreatment with the two H. inuloides extracts attenuated the increase in the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) observed in CCl₄-induced liver injury. The protective effect was confirmed by the analysis of tissue slides stained with hematoxylin-eosin and periodic acid/Schiff’s reagent. Additionally, the two extracts are scavengers to the superoxide radical as was observed by electron paramagnetic resonance. Due to the fact that the methanolic extract resulted in a better protective effect in the previous experiments, it was used to investigate in more detail the mechanism of hepatoprotection. Quercetin, one of the main components of the extract, with known hepatoprotective and antioxidant activity was used as a positive control. Pretreatment of animals with the methanolic extract or quercetin, was associated with the prevention of 4-hydroxynonenal and 3-nitrotyrosine increase in the liver, two markers of oxidative stress. Furthermore, the decrease in the activity of several antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase in CCl₄-induced liver injury was alleviated by the pretreatment with H. inuloides methanolic extract or quercetin. These results suggest that the hepatoprotective capacity of H. inuloides methanolic extract is associated with its antioxidant properties, which would also explain the biomedical properties attributed to this plant.     

Trillin Reduces Liver Chronic Inflammation and Fibrosis in Carbon Tetrachloride (CCl4) Induced Liver Injury in Mice

Trillin is an active ingredient isolated from Dioscorea nipponica Makino. This study investigated the anti-inflammatory and anti-fibrosis effects of trillin on CCl₄-induced hepatotoxicity in C57BL/6 mice. Chronic inflammation and fibrosis were induced by intraperitoneal administration of CCl₄ 0.5 μL/g of body weight twice a week for 6 weeks. Trillin (50 mg/kg, 100 mg/kg) was administered by gavage for 12 days before finishing the CCl₄ induction. Aspartate amino-transferase (AST) and glutamic-pyruvic transaminase (ALT) in serum were determined by AST and ALT kits. Superoxidase dismutase (SOD) activity and malondialdehyde (MDA) levels in serum were assayed by SOD and MDA kits. Meanwhile, the levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in serum were detected by enzyme-linked immunosorbent assay (ELISA) method. Pathological changes were observed by hematoxylin-eosin (HE) staining. The proteins of the NF-κB pathway and the TGF-β/Smad pathway were measured by western blot. The trillin-treated group exhibited reduced AST, ALT, MDA, IL-6, TNF-α, and IL-1β, and increased SOD. Histological analyses of the trillin-treated group exhibited reduced inflammatory process and prevented liver fibrosis. Western blot analyses of the trillin-treated group showed reduced NF-κB pathway and TGF-β/Smad pathway. Significance: Based on the results of the present study, trillin can be used as a potential anti-inflammatory drug for chronic hepatic inflammation.     

Attenuation of CCl4-induced hepatic oxidative stress in rat by Launaea procumbens

Antioxidant effects of Launaea procumbens methanol extract (LPME) were evaluated against CCl₄-induced oxidative stress in liver of rat. 48 male rats were equally divided in to 8 groups (06 rats each). Group I (control) remained untreated, while Group II was given vehicles (olive oil and DMSO). Animals of Groups III, IV, V, VI and VII were injected intraperitoneally with CCl₄ (3 ml/kg b.w.; i.p., 20% CCl₄/olive oil) twice a week for four weeks. Group III received only CCl₄ while Group IV was given rutin (50 mg/kg b.w.). Group V, VI and VII were administered LPME at a dose of 100, 150 and 200 mg/kg b.w., respectively. Animals of Group VIII received LPME (200 mg/kg b.w.) alone. Oxidative stress induced with CCl₄ in liver was evident by a significant increase in triglycerides, total cholesterol, LDL-cholesterol, and enzymatic activities of AST, ALT, ALP, LDH, γ-GT activities in serum. Level of lipid peroxidation, nitrite, and hydrogen peroxide concentration, DNA injuries in liver samples was also increased with CCl₄. GSH concentration in liver was significantly decreased, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GST, GSR, QR. Co-treatment of rats with LPME and rutin prevented all the changes observed with CCl₄. Hepatic lesions and telomerase activity induced with CCl₄ was also suppressed with LPME and rutin. It is suggested that LPME effectively prevented the CCl₄-induced oxidative injuries in liver, possibly through antioxidant and/or free radical scavenging effects of flavonoids and phenolic compounds in the extract.     

Antioxidant potential of rat liver in experimental infection with Fasciola hepatica

The aim of this paper is to assess the antioxidant properties of rat liver in the course of acute and chronic fasciolosis. Wistar rats were infected per os with 30 metacercariae of Fasciola hepatica. Liver activities of antioxidant enzymes and concentrations of non-enzymatic antioxidants were determined at 4, 7, and 10 weeks post-infection. Activities of superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R) were decreased, catalase (CAT) activity was increased and non-enzymatic antioxidant concentrations (reduced glutathione, vitamins C, E and A) were reduced simultaneously with enhancement of lipid peroxidation processes as evidenced by increased levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Changes in the antioxidant abilities of the liver and in the phospholipid structure of the cell membrane were accompanied by rising activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as markers of liver damage.     

铜过量小鼠肝损伤模型的建立及各项指标的观察研究

目的探讨昆明小鼠在不同剂量的铜负荷时所引起的肝脏抗氧化水平和相关病理的改变。方法32只昆明小鼠平均分为4组，第1组为对照组，每天灌胃生理盐水2次，第2、3、4组作为实验组，分别用不同浓度（12．8、25．6和38．4mg／mL）的硫酸铜每日灌胃2次，16周后，观察肝组织中丙二醛（MDA）含量、超氧化物歧化酶（SOD）以及谷胱甘肽过氧化物酶（GSH-Px）的活性，测定血清谷丙转氨酶（ALT）和谷草转氨酶（AST）以及血清和肝组织中铜含量，并做肝脏病理以及电镜检查。结果与正常对照组相比，实验组肝组织中MDA含量明显升高（P〈0．05），而SOD和GSH-Px活性明显下降（P〈0．05）；血清ALT、AST活性以及血清、肝脏铜含量明显升高（P〈0．05）；病理组织学检查可见高剂量铜灌胃组小鼠肝细胞变性坏死以及少量铜颗粒沉积：电镜提示肝细胞核、线粒体等细胞器异常．并可见铜颗粒。结论过量的铜可对肝脏造成损害，其机制可能与释放出的铜离子介导脂质过氧化而造成肝脏损害有关。其病变过程与Wilson’s病相似，可为进一步研究铜代谢异常等疾病提供动物模型。     

Resolvin D1 attenuates CCl4-induced acute liver injury involving up-regulation of HO-1 in mice

Acute hepatic failure involves in excessive oxidative stress and inflammatory responses, leading to a high mortality due to lacking effective therapy. Resolvin D1 (RvD1), an endogenous lipid mediator derived from polyunsaturated fatty acids, has been shown anti-inflammatory and anti-oxidative actions, however, whether RvD1 has protective effects on hepatic failure remains elusive. In this study, the roles and molecular mechanisms of RvD1 were explored in carbon tetrachloride (CCl₄)-induced acute liver injury. Our results showed that RvD1 protected mice against CCl₄-induced hepatic damage, as evaluated by reduced aminotransferase activities and malondialdehyde content, elevated glutathione and superoxide dismutase activities, and alleviated hepatic pathological damage. Moreover, RvD1 significantly attenuated serum tumor necrosis factor-α and interleukin-6 levels as well as hepatic myeloperoxidase activity, whereas enhanced serum IL-10 level in CCl₄-administered mice. Further, RvD1 markedly up-regulated the expression and activity of heme oxygenase-1 (HO-1). However, inhibition of HO-1 activity reversed the protective effects of RvD1 on CCl₄-induced liver injury. These results suggest that RvD1 could effectively prevent CCl₄-induced liver injury by inhibition of oxidative stress and inflammation, and the underlying mechanism may be related to up-regulation of HO-1.     

葡萄籽原花青素减轻小鼠急性化学性肝损伤

 背景：目前关于葡萄籽原花青素的研究很多,但是对小白鼠化学性肝脏损伤的保护作用研究较少。 目的:探讨葡萄籽原花青素对小白鼠化学性肝损伤的保护作用。 方法:复制两种小白鼠化学性肝损伤的动物模型,用五种不同剂量葡萄籽原花青素分别灌胃,取各组小白鼠血清以及肝脏组织并测量血清中ALT、AST以及肝脏组织中SOD、MDA的含量,取各组小白鼠肝脏组织做病理切片观察。 结果:小白鼠CCl4和酒精性肝损伤动物模型均复制成功,模型组各项指标与空白对照组比较,差异均有显著性（P＜0.01）。两种肝损伤实验中各给药组肝脏MDA含量随着给药剂量的增加而下降,而且与模型组比较差异均有显著性（P＜0.05）;各给药组SOD含量随着给药剂量的增加而增加,与模型组比较差异均有显著性（P＜0.05）;各给药组血清中ALT、AST含量随着给药剂量的增加而下降,与模型组比较除10mg/kg时ALT含量差异无显著性（P>0.05）之外其他各给药组与模型组比较差异均有显著性（P＜0.05）。 结论:GSP对小白鼠CCl4肝损伤有一定的保护作用;GSP对酒精性肝损伤有一定的保护作用;在一定范围内GSP剂量与肝脏保护作用有一定的剂量反应关系。