Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic nephropathy is a common cause of end-stage renal disease. The administration of an oral adsorbent, AST-120, prevents the progression of chronic renal failure in uremic rats and undialyzed uremic patients. This study was designed to determine if AST-120 slows the progression of diabetic nephropathy using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetic mellitus. At 21 weeks of age the OLETF rats were divided into 2 groups: AST-120-administered OLETF rats (n = 7), and control OLETF rats (n = 7). LETO rats, which are genetically similar to the OLETF rats but not diabetic, were also included. After the oral administration of AST-120 for 65 weeks, renal function and pathological changes were investigated in the 3 groups. The administration of AST-120 to the OLETF rats attenuated the progression of glomerular sclerosis, interstitial fibrosis, tubular injury as well as renal dysfunction, and reduced the serum and urinary levels of indoxyl sulfate. Furthermore, AST-120 administration reduced the interstitial expression of transforming growth factor (TGF)-beta(1) and tissue inhibitor of metalloproteinase (TIMP)-1, as well as interstitial infiltration of macrophages. The TGF-beta(1)-stained interstitial area showed positive correlations with the interstitial fibrosis area, the number of TIMP-1-positive cells, and the number of macrophages, and showed a negative correlation with creatinine clearance. In conclusion, AST-120 reduced the interstitial expression of TGF-beta(1) and TIMP-1, and the interstitial infiltration of macrophages, and ameliorates the progression of diabetic nephropathy in OLETF rats.
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PMID:Oral adsorbent AST-120 ameliorates interstitial fibrosis and transforming growth factor-beta(1) expression in spontaneously diabetic (OLETF) rats. 1087 8

To assess the effects of anti-TNF-alpha antibody (infliximab) in experimental steatohepatitis induced by methionine- and choline-deficient (MCD) diet. The study included thirty rats. One group received normal rat food, and two groups received MCD diet. The treatment group received a single dose intra-peritoneal infliximab (4 mg/kg), at week 8. MCD diet increased levels of AST, ALT, TNF-alpha, TGF-beta(1), tissue and plasma MDA (p < 0.05 for each). Moreover, it led to steatosis, ballooning degeneration, inflammation, fibrosis and increased actin expression, histopathologically (p < 0.05 for each). In this experimental steatohepatitis anti-TNF-alpha antibody decreased the levels of AST, ALT, TGF-beta(1) and plasma and tissue MDA (p < 0.05 for each). Moreover, inflammation, necrosis, actin expression and fibrosis decreased in anti-TNF-alpha group compared to placebo group (p < 0.05 for each). This study indicates that anti-TNF-alpha antibody is effective on necrosis, inflammation and fibrosis in the experimental model of non-alcoholic steatohepatitis, induced by MCD diet.
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PMID:The treatment with antibody of TNF-alpha reduces the inflammation, necrosis and fibrosis in the non-alcoholic steatohepatitis induced by methionine- and choline-deficient diet. 1806 56

Sickle cell anemia (SCA) is characterized by a marked endothelial dysfunction, owing to many factors. Arginine metabolism can be related to the inflammatory chronic state presented by patients, playing a key role in their clinical outcome and vascular endothelium. We investigated the serum arginase levels in 50 SCA patients (22 men and 28 women, mean age of 17 +/- 10.5 years) and 28 healthy controls. Serum arginase levels were associated with biochemical hemolysis markers and cytokines involved in Th17 response, as well as levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1). Arginase concentrations were higher in SCA patients, compared with controls (p = 0.005), and were significantly and positively associated with total bilirubin (p = 0.004), indirect bilirubin (p = 0.04), and aspartate aminotransferase (AST; p = 0.039) in the SCA patient group. Moreover, arginase was significantly and positively associated with transforming growth factor-beta (TGF-beta; p = 0.008) among SCA patients. sICAM-1 was significantly and positively associated to reticulocytes (p = 0.014) and AST (p = 0.04). sVCAM-1 was likewise associated with lactate dehydrogenase (p = 0.03). These data suggest a new insight into arginase metabolism, as we show here a shift in arginine catabolism, where TGF-beta may induces the arginase pathway instead of the nitric oxide pathway and a possible involvement of the vascular activation and the serum arginase in chronic hemolysis among SCA patients. Additional studies should be carried out in order to investigate the mechanisms by which TGF-beta participates in the metabolism of arginase in SCA patients.
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PMID:Arginase levels and their association with Th17-related cytokines, soluble adhesion molecules (sICAM-1 and sVCAM-1) and hemolysis markers among steady-state sickle cell anemia patients. 2040 89

Liver fibrosis is a major cause of liver failure, but treatment remains ineffective. In the present study, we investigated the mechanisms and anti-hepatofibrotic activities of asiatic acid (AA) in a rat model of liver fibrosis induced by carbon tetrachloride (CCl(4)) and in vitro in TGF-beta1-stimulated rat hepatic stellate cell line (HSC-T6). Treatment with AA significantly attenuated CCl(4)-induced liver fibrosis and functional impairment in a dosage-dependent manner, including blockade of the activation of HSC as determined by inhibiting de novo alpha smooth muscle actin (a-SMA) and collagen matrix expression, and an increase in ALT and AST (all p<0.01). The hepatoprotective effects of AA on fibrosis were associated with upregulation of hepatic Smad7, an inhibitor of TGF-beta signaling, thereby blocking upregulation of TGF-beta1 and CTGF and the activation of TGF-beta/Smad signaling. The anti-fibrosis activity and mechanisms of AA were further detected in vitro in HSC-T6. Addition of AA significantly induced Smad7 expression by HSC-T6 cells, thereby inhibiting TGF-beta1-induced Smad2/3 activation, myofibroblast transformation, and collagen matrix expression in a dosage-dependent manner. In contrast, knockdown of Smad7 in HSC-T6 cells prevented AA-induced inhibition of HSC-T6 cell activation and fibrosis in response to TGF-beta1, revealing an essential role for Smad7 in AA-induced anti-fibrotic activities during liver fibrosis in vivo and in vitro. In conclusion, AA may be a novel therapeutic agent for liver fibrosis. Induction of Smad7-dependent inhibition of TGF-beta/Smad-mediated fibrogenesis may be a central mechanism by which AA protects liver from injury.
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PMID:Asiatic acid inhibits liver fibrosis by blocking TGF-beta/Smad signaling in vivo and in vitro. 2236 27