Home About us Contact
|
Home About us Contact | ||
|
|
||
Alanine Aminotransferase Activities (alanine + aminotransferase_activity)
Selected AbstractsAntifibrotic effects of tetrandrine on hepatic stellate cells and rats with liver fibrosisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2007Yi-Chao Hsu Abstract Background:, Anti-inflammation strategies are one of the proposed therapeutic approaches to hepatic fibrosis. Tetrandrine (C38H42O8N2, molecular weight: 622; Tet), an alkaloid isolated from the Chinese medicinal herb Stephania tetrandra, has been shown to exert anti-inflammatory activity in pulmonary diseases. The purpose of the present study was to investigate the in vitro and in vivo effects of Tet on hepatic fibrosis. Methods:, A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with transforming growth factor-,1 (TGF-,1) or tumor necrosis factor-, (TNF-,). The inhibitory effects of Tet on the nuclear factor ,B (NF,B) signaling cascade and molecular markers including intercellular adhesion molecule-1 (ICAM-1) and ,-smooth muscle actin (,-SMA) secretion were assessed. Fibrosis was induced by dimethylnitrosamine (DMN) administration in rats for 4 weeks. Fibrotic rats were randomly assigned to one of the four groups: vehicle (0.7% carboxyl methyl cellulose, CMC), Tet (1 mg/kg), Tet (5 mg/kg), or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting after 1 week of DMN administration. At the end of the study, liver tissues were scored for fibrosis and analyzed for molecular markers of fibrosis. Results:, Tetrandrine (0.5,5.0 µmol/L) concentration-dependently inhibited NF,B transcriptional activity induced by TNF-,, including I,B, phosphorylation and mRNA expressions of ICAM-1 in HSC-T6 cells. In addition, Tet also inhibited TGF-,1-induced ,-SMA secretion and collagen deposition in HSC-T6 cells. Fibrosis scores of livers from DMN-treated rats with high-dose Tet (1.3 ± 0.3) were significantly reduced in comparison with DMN-treated rats receiving saline (2.0 ± 0.2). Hepatic collagen content of DMN rats was significantly reduced by either Tet or silymarin treatment. Double-staining results showed that ,-SMA- and NF,B-positive cells were decreased in the fibrotic livers by Tet and silymarin treatment. In addition, mRNA expression of ICAM-1, ,-SMA, and TGF-,1 was attenuated by Tet treatment. Moreover, levels of plasma aspartate aminotransferase and alanine aminotransferase activities were reduced by Tet and silymarin treatment. Conclusion:, Tetrandrine exerts antifibrotic effects in both HSC-T6 cells and in rats with DMN-induced fibrosis. [source] A caspase inhibitor, IDN-6556, ameliorates early hepatic injury in an ex vivo rat model of warm and cold ischemia,LIVER TRANSPLANTATION, Issue 3 2007Niel C. Hoglen This study examined the efficacy of the caspase inhibitor, IDN-6556, in a rat model of liver ischemia-reperfusion injury. Livers from male Sprague-Dawley rats were reperfused for 120 minutes after 24 hours of 4°C cold storage in University of Wisconsin solution. Portal blood flow measurements estimated sinusoidal resistance, and bile production, alanine aminotransferase activities, and Suzuki scores were evaluated as parameters of hepatocyte/liver injury. Treated livers were exposed to 25 or 50 ,M of IDN-6556 in University of Wisconsin storage solution and/or the perfusate. All treatment regimens with IDN-6556 significantly improved portal blood flow measured at 120 minutes, and significant improvements were seen as early as 30 minutes when inhibitor was also present in the perfusate (P < 0.01). All treatment groups with IDN-6556 significantly increased bile production by 3-4-fold compared with controls (P < 0.01), and reductions in alanine aminotransferase activities were seen within 90 minutes of reperfusion (P < 0.05). These data were confirmed by improved Suzuki scores (less sinusoidal congestion, necrosis, and vacuolization) in all treated groups. Livers from the IDN-6556,treated groups had markedly reduced caspase activities and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-positive cells, suggesting reductions in apoptosis. IDN-6556 present in cold storage media ameliorated liver injury due to cold ischemia and reperfusion injury and may be a rational therapeutic approach to reduce the risk of liver ischemia in the clinical setting. Liver Transpl 13: 361,366, 2007. © 2007 AASLD. [source] Quantitative dietary threonine requirement of juvenile Pacific white shrimp, Litopenaeus vannamei (Boone) reared in low-salinity waterAQUACULTURE RESEARCH, Issue 8 2009Ming-Yan Huai Abstract An 8-week feeding trial was conducted to determine the threonine requirement of juvenile Pacific white shrimp Litopenaeus vannamei (Boone) in low-salinity water (0.50,1.50 g L,1). Diets 1,6 were formulated to contain 360 g kg,1 crude protein with fish meal, wheat gluten and pre-coated crystalline amino acids with six graded levels of l -threonine (9.9,19.0 g kg,1 dry diet). Diet 7, which was served as a reference, contained only intact proteins (fish meal and wheat gluten). Each diet was randomly assigned to triplicate groups of 30 shrimps (0.48±0.01 g), each four times daily. Shrimps fed the reference diet had similar growth performance and feed utilization efficiency compared with shrimps fed the diets containing 13.3 g kg,1 or higher threonine. Maximum specific growth rate (SGR) and protein efficiency ratio were obtained at 14.6 g kg,1 dietary threonine, and increasing threonine beyond this level did not result in a better performance. Body compositions, triacyglycerol and total protein concentrations in haemolymph were significantly affected by the threonine level; however, the threonine contents in muscle, aspartate aminotransferase and alanine aminotransferase activities in haemolymph were not influenced by the dietary threonine levels. Broken-line regression analysis on SGR indicated that optimal dietary threonine requirement for L. vannamei was 13.6 g kg,1 dry diet (37.8 g kg,1 dietary protein). [source] Immunohistochemical Characterization of Hepatic Malondialdehyde and 4-Hydroxynonenal Modified Proteins During Early Stages of Ethanol-Induced Liver InjuryALCOHOLISM, Issue 6 2003Brante P. Sampey Background: Chronic ethanol consumption is associated with hepatic lipid peroxidation and the deposition or retention of aldehyde-adducted proteins postulated to be involved in alcohol-induced liver injury. The purpose of this study was to characterize hepatocellular formation of aldehyde-protein adducts during early stages of alcohol-induced liver injury. Methods: Female Sprague Dawley® rats were subjected to the intragastric administration of a low-carbohydrate/high-fat total enteral nutrition diet or a total enteral nutrition diet containing ethanol for a period of 36 days. Indexes of hepatic responses to ethanol were evaluated in terms of changes in plasma alanine aminotransferase activity, hepatic histopathologic analysis, and induction of cytochrome P-4502E1 (CYP2E1). Immunohistochemical methods were used to detect hepatic proteins modified with malondialdehyde (MDA) or 4-hydroxynonenal (4-HNE) for subsequent quantitative image analysis. Results: After 36 days of treatment, rats receiving the alcohol-containing diet displayed hepatic histopathologies characterized by marked micro- and macrosteatosis associated with only minor inflammation and necrosis. Alcohol administration resulted in a 3-fold elevation of plasma alanine aminotransferase activity and 3-fold increases (p < 0.01) in hepatic CYP2E1 apoprotein and activity. Quantitative immunohistochemical analysis revealed significant (p < 0.01) 5-fold increases in MDA- and 4-HNE modified proteins in liver sections prepared from rats treated with alcohol. The MDA- or 4-HNE modified proteins were contained in hepatocytes displaying intact morphology and were colocalized primarily with microvesicular deposits of lipid. Aldehyde-modified proteins were not prevalent in parenchymal or nonparenchymal cells associated with foci of necrosis or inflammation. Conclusions: These results suggest that alcohol-induced lipid peroxidation is an early event during alcohol-mediated liver injury and may be a sensitizing event resulting in the production of bioactive aldehydes that have the potential to initiate or propagate ensuing proinflammatory or profibrogenic cellular events. [source] Review article: management of patients with chronic hepatitis C virus infection and ,normal' alanine aminotransferase activityALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2006S. ZEUZEM Summary Background Hepatitis C virus infection, a major cause of chronic liver disease, occurs with normal serum alanine aminotransferase activity in approximately 25% of patients. These patients have historically remained untreated but substantial evidence indicates liver damage, progression of disease and impaired quality of life in some individuals. Aim To review the current management of patients with chronic hepatitis C and normal alanine aminotransferase activity. Methods This review represents the summary of discussions at a Clinical Workshop with a comprehensive literature searching of available databases (PubMed and Embase). Results Current limits defining normal serum alanine aminotransferase activity are not representative of a ,healthy' status. Most patients with hepatitis C and normal alanine aminotransferase levels have histologically proven liver damage that, although generally mild, may be significant (,F2) in up to 20% of patients and progresses at approximately 50% of the rate in patients with elevated alanine aminotransferase levels. Some patients have persistently normal alanine aminotransferase activity and may have a more benign outcome, but a significant proportion (,20%) experience periods of increased serum alanine aminotransferase activity which may be associated with enhanced disease progression. Conclusions A treatment approach that considers host and virus-related variables and optimizes patient and cost benefits may therefore provide more effective management of patients with chronic hepatitis C and normal alanine aminotransferase activity. [source] | ||||||||||