Markers In Liver Tissue Research Articles

Hepatoprotective effect of 17β-estradiol as antioxidant modulators against stress damage.

Background:Liver is one of the most important organs affected by exercise. According to the literature a few study to date has investigated the effects of estrogen supplementation on exercise-induced oxidative stress in liver tissue of rats.Objectives:We aimed to investigate the effects of estrogen supplementation on oxidative stress markers in liver tissue of exercised rats.Materials and Methods:Male rats (n = 35) were divided as estrogen supplemented (n = 18) and non-supplemented groups (n = 17); these groups were further divided as rest and eccentric exercised groups. Eccentric exercise groups were further divided as rats killed after 1 hour and 48 hours of eccentric exercise. Estrogen (10 mg/kg) was administered subcutaneously for 30 days. Eccentric exercise was applied as treadmill run (15° downhill, 20 m/min) consisting of periods of "5 min" run and 2 min rest repeated 18 times. The rat liver was examined biochemically and histologically. Activities of GST, GSH-Px, CAT, SOD and MDA concentration were also measured spectrophotometrically.Results:Some disruptions were detected in experimental groups compared with the control group. Additionally, exercise training caused an increase in SOD and decrease in GSH-Px activities in some experimental groups. SOD activities increased significantly in group 3 (Estrogen (-), eccentric exercise (+) killed (after 1 h), compared with group 5 (Estrogen (-), eccentric exercise (+) killed (after 48 h). On the other hand, GSH-Px activities were also significantly decreased in groups 3, 4 and 5 compared with the control group. Leukocyte infiltration in liver increased after 48 hours compared with after 1 hour and estrogen supplementation was not able to prevent this infiltration.Conclusions:Estrogen seemed to be not very effective to prevent eccentric exercise-induced liver damage.

Methylmercury-induced oxidative stress in rainbow trout (Oncorhynchus mykiss) liver: ameliorating effect of vitamin C.

The present study was undertaken to evaluate methylmercury-induced alterations in hepatic enzymes and oxidative stress markers in liver tissue of rainbow trout (Oncorhynchus mykiss) by using a perfusion method, and to explore possible protective effect of vitamin C against these alterations. Forty-eight fish were divided into six groups containing control, test, and amelioration groups. The liver of fish in the test groups were exposed to different doses of methylmercury, i.e., 0.6, 1.2, and 2.4μgL(-1), respectively, for 120min. In the amelioration group, liver was treated with vitamin C (17.2μgL(-1)) along with high dose (2.4μgL(-1)) of methylmercury. The results of the present study showed that exposure with 0.6, 1.2, and 2.4μgL(-1) of methylmercury significantly increased (p < 0.05) hepatic enzyme activities (alanine transaminase (ALT), aspartate transaminase (AST), and Lactate dehydrogenase (LDH)) and malondialdehyde (MDA) level, as a marker of lipid peroxidation. On the other hand, the concentration of reduced glutathione (GSH) and total antioxidant capacity of the liver decreased (p < 0.05) in the methylmercury-exposed groups when compared to the control group. Pearson's correlation analysis revealed a positive correlation between MDA concentration and ALT, AST, and LDH activities in the methylmercury groups, suggesting that the enhanced lipid peroxidation may be linked to hepatic damage caused by methylmercury. Treatment with vitamin C in methylmercury-exposed group led to a significant decrease (p < 0.05) in MDA concentration and hepatic enzyme activities and significant increase (p < 0.05) in levels of GSH and total antioxidant capacity. The values of measured parameters in the methylmercury + vitamin C group were comparable to those of the control group. The results of the present study demonstrated that methylmercury exposure induces oxidative stress in the liver of rainbow trout and treatment with vitamin C can protect fish liver against this oxidative insult.

Digital quantitation of HCC-associated stem cell markers and protein quality control factors using tissue arrays of human liver sections

The most common type of liver cancer, hepatocellular carcinoma (HCC), affects over 500,000 people in the world. In the present study, liver tumor resections were used to prepare tissue arrays to examine the intensity of fluorescence of IHC stained stem cell markers in liver tissue from malignant HCC tumors and accompanying surrounding non-tumor liver. We hypothesized that a correlation exists between the fluorescence intensity of IHC stained HCC and surrounding non-tumor liver compared to liver tissue from a completely normal liver. 120 liver resection specimens (including four normal controls) were placed on a single slide to make a tissue array. They were examined by digitally quantifying the intensity of fluorescence using immuno-histochemically stained stem cell markers and protein quality control proteins. The stem cell markers were OCT3/4, Nanog, CD133, pEZH2, CD49F and SOX2. The protein quality control proteins were FAT10, UBA-6 and ubiquitin. The data collected was used to compare normal liver tissue with HCCs and parent liver tissue resected surgically using antibodies to stem cell markers and quality control protein markers. The measurements of the stem cell marker CD133 indicated an increase of fluorescence intensity for both the parent liver tissue and the HCC liver tissues. The other stem cell markers changed as follows: Nanog and OCT3/4 were decreased in both the HCCs and the parent livers; PEZH2 was reduced in the HCCs; SOX2 was increased in the parent livers compared to the controls; and CD49f was decreased in HCCs only. Protein quality control markers FAT10 and ubiquitin were downregulated in both the HCCs and the adjacent non-tumor tissue compared to the controls. UBA6 was increased in both the HCCs and the parent livers, and the levels were higher in the HCCs compared to the parent livers.

Viral Hepatitis Markers in Liver Tissue in Relation to Serostatus in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) incidence is increasing in the United States. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of HCC. Hepatitis infection in patients with HCC is generally diagnosed by serology, which is not always consistent with the presence of HBV and HCV in the liver. The relationship of liver viral status to serostatus in hepatocarcinogenesis is not fully understood. HBV and HCV were evaluated in formalin-fixed, paraffin-embedded liver tissue specimens in a retrospective study of 61 U.S. HCC cases of known serologic status. HBV DNA and HCV RNA were detected by PCR, reverse transcription PCR (RT-PCR), and pyrosequencing, and HBsAg and HBcAg were evaluated by immunohistochemistry. Viral markers were detected in the liver tissue of 25 of 61 (41%) HCC cases. Tissue viral and serologic status were discordant in 27 (44%) cases, including those with apparent "occult" infection. Specifically, HBV DNA was detected in tissue of 4 of 39 (10%) serum HBsAg (-) cases, including 1 anti-HCV(+) case; and HCV RNA was detected in tissue of 3 of 42 (7%) anti-HCV seronegative cases, including two with serologic evidence of HBV. Viral hepatitis, including HBV-HCV coinfection, may be unrecognized in up to 17% of patients with HCC when based on serology alone. Further research is needed to understand the clinical significance of viral makers in liver tissue of patients with HCC in the absence of serologic indices. The contribution of HBV and HCV to the increasing incidence of HCC in the United States may be underestimated.

Effect of Rosiglitazone on Liver Structure and Function in Genetically Diabetic Akita Mice

Genetically diabetic Akita mice, kept on a high-fat and high-cholesterol diet, and treated with the peroxisome proliferator-activated receptor-γ agonist rosiglitazone (10mg/kg per day during 4months), displayed rosiglitazone-induced side effects, similar to those observed in patients, including weight and fat gain and early signs of hypertrophic cardiomyopathy. As several cases of hepatotoxicity were reported in patients receiving rosiglitazone treatment, this study evaluated whether rosiglitazone also induced hepatotoxicity in these diabetic animals. Liver structure and function was analysed in wild-type and rosiglitazone-treated and untreated Akita mice, kept for 4months on the high-fat and high-cholesterol diet. Decreased circulating levels of the liver enzymes aspartate and alanine aminotransferase and increased levels of alkaline phosphatases were observed upon rosiglitazone treatment, whereas liver weight was markedly increased. Rosiglitazone administration was associated with liver steatosis, as demonstrated by triglyceride accumulation. However, gene expression of steatosis markers in liver tissue was not markedly affected by rosiglitazone treatment, while expression of fatty acid transport protein was reduced by rosiglitazone treatment, suggesting an impairment of the fatty acid β-oxidation pathway. mRNA expression of pro- and anti-oxidant enzymes and liver 3-nitrotyrosine content was not affected. Furthermore, gene and protein expression of macrophage markers and of cell adhesion molecules did not indicate progression to steatohepatitis, whereas an unaltered collagen deposition did not suggest steatofibrosis. In conclusion, rosiglitazone treatment of diabetic Akita mice induced liver steatosis without, however, progression to more advanced stages of liver disease.

Effects of Grape Seed Polyphenols on Oxidative Damage in Liver Tissue of Acutely and Chronically Exercised Rats

The objective of the present study was to investigate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant defense markers in liver tissue of acutely and chronically exercised rats. Rats were randomly assigned to six groups: Control (C), Control Chronic Exercise (CE), Control Acute Exercise (AE), GSE-supplemented Control (GC), GSE-supplemented Chronic Exercise(GCE) and GSE-supplemented Acute Exercise (GAE). Rats in the chronic exercise groups were subjected to a six-week treadmill running and in the acute exercise groups performed an exhaustive running. Rats in the GSE supplemented groups received GSE (100 mg.kg(-1) .day(-1) ) in drinking water for 6 weeks. Liver tissues of the rats were taken for the analysis of malondialdehyde (MDA), nitric oxide (NO) levels and total antioxidant activity (AOA) and xanthine oxidase (XO) activities. MDA levels decreased with GSE supplementation in control groups but increased in acute and chronic exercise groups compared to their non-supplemented control. NO levels increased with GSE supplementation. XO activities were higher in AE group compared to the CE group. AOA decreased with GSE supplementation. In conclusion, while acute exercise triggers oxidative stress, chronic exercise has protective role against oxidative stress. GSE has a limited antioxidant effect on exercise-induced oxidative stress in liver tissue.

The effect of extract of ginkgo biloba leaf during the formation of HBV-related hepatocellular carcinoma

To investigate the effect of extract of ginkgo biloba leaf (EGb) during the formation of HBV-related hepatocellular carcinoma (HCC). 99 HBV transgenic mice were randomly divided into control group, high-dose group, low-dose group. High-dose group and low-dose group were intraperitoneal injected 35mg/(kg x d) and 17.5 mg/(kg x d) of the shuxuening injection. Control group without special treatment. The serological markers and immunohistochemical markers in liver tissue will be done at the first 12 months and 18 months. (1) HBV transgenic mice can be found HCC at the 18 months. The incidence of HCC was lower in high-dose group and low-dose group, there was statistically different among the three groups. (2) The semi-quantitative scoring of liver HBx expression was highest in the control group at the 12 months. The semi-quantitative scoring of liver HBx, p53 and Bcl-2 expression was highest in the control group at the 18 months. They all appeared statistically different among the three groups. (3) Spearman correlation analysis showed that HCC incidence and liver tissue HBx, p53, Bcl-2 expression was a certain degree of positive correlation, r was 0.536, 0.487 and 0.403, P < 0.05. EGb can reduced the incidence of the HCC with HBV transgenic mice. The reason may be that the EGb can reduce liver HBx, p53, Bcl-2 protein expression in the HBV transgenic mice.

Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation

Ischemia/reperfusion (IR) injury in transplanted livers contributes to organ dysfunction and failure and is characterized in part by loss of NO bioavailability. Inhalation of NO is nontoxic and at high concentrations (80 ppm) inhibits IR injury in extrapulmonary tissues. In this prospective, blinded, placebo-controlled study, we evaluated the hypothesis that administration of inhaled NO (iNO; 80 ppm) to patients undergoing orthotopic liver transplantation inhibits hepatic IR injury, resulting in improved liver function. Patients were randomized to receive either placebo or iNO (n = 10 per group) during the operative period only. When results were adjusted for cold ischemia time and sex, iNO significantly decreased hospital length of stay, and evaluation of serum transaminases (alanine transaminase, aspartate aminotransferase) and coagulation times (prothrombin time, partial thromboplastin time) indicated that iNO improved the rate at which liver function was restored after transplantation. iNO did not significantly affect changes in inflammatory markers in liver tissue 1 hour after reperfusion but significantly lowered hepatocyte apoptosis. Evaluation of circulating NO metabolites indicated that the most likely candidate transducer of extrapulmonary effects of iNO was nitrite. In summary, this study supports the clinical use of iNO as an extrapulmonary therapeutic to improve organ function following transplantation.