Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AIM:To investigate effect of losartan, an AT1 receptor antagonist, on hepatic fibrosis induced by CCl(4); and to determine whether or not AT1 receptors are expressed on hepatic stellate cells. METHODS AND RESULTS:Fifty male Sprague-Dawley rats, weighing (180 plus minus20)g, were randomized into five groups (control group, model group, and three losartan treated groups), in which all rats were given the subcutaneous injection of 40% CCl(4)(every 3 days for 6 weeks) except for rats of control group. Rats of losartan-treated groups were treated with losartan (20 mg/kg, 10 mg/kg, 5 mg/kg, daily gavage). After 6 weeks liver tissue and serum samples of all rats were examined. Serum hyaluronic acid (HA), procollagen type III (PC III) were detected by radioimmunoassays. van Giesion collagen staining was used to evaluate the extracellular matrix of rats with liver fibrosis. The expression of AT1 receptors, transforming growth factor-beta (TGF-beta), and alpha-smooth muscle actinalpha-SMA) in liver tissue were determined by immunohistochemical techniques. Compared with model group, serum ALT and AST of losartan-treated groups were significantly reduced (italic>t = 4.20,P < 0.01 and italic>t = 4.57,P < 0.01). Serum HA and PC III also had significant differences (italic>t = 3.53,P<0.01 and t=2.20, P<0.05). The degree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors, TGF-beta, and alpha-SMA in liver tissue.CONCLUSION:AT1 receptor antagonist, losartan, could limit the progression of the hepatic fibrosis induced by CCl(4). The mechanism may be related to the decrease in the expression of AT1 receptors and TGF-beta, ameliorating the injury of hepatocytes; activation of local renin-angiotensin system might relate to hepatic fibrosis; and during progression of fibrosis, activated hepatic stellate cells might express AT1 receptors.
 ...
PMID:Effects of AT1 receptor antagonist, losartan, on rat hepatic fibrosis induced by CCl(4). 1181 43

Oxidative burst provides the mechanism for specialized phagocytes, such as granulocytes or monocytes, to kill invading microorganisms through generation of superoxide anions. However, the oxidants generated during the burst damage DNA of the phagocytes and neighboring cells. Human blood leukocytes treated with phorbol myristate acetate (PMA) are considered to represent the experimental model of induction of oxidative burst. We recently reported that DNA damage in PMA-treated leukocytes is assessed by cytometric analysis of the induction of histone H2AX phosphorylation and Ataxia Telangiectasia Mutated (ATM) activation. In the present study we observed that hyaluronic acid (HA) of average molecular weight (MW) 5.4x10(6) and 2x10(6) at 0.1% (w/v) concentration significantly attenuated H2AX phosphorylation and ATM activation induced in leukocytes during oxidative burst. HA also reduced the intracellular level of PMA-induced reactive oxidants as measured by the ability of cells to oxidize 2',7'-dihydro-dichlorofluorescein-diacetate. No such effect was seen with HA of 6x10(4) MW. The data are consistent with earlier observations that HA of high MW protects DNA from oxidative damage induced by endo- or exogenous oxidants. The anti-oxidant effect of HA seen during oxidative burst also explains its anti-inflammatory effect when used to treat arthritic joints.
 ...
PMID:Attenuation of the oxidative burst-induced DNA damage in human leukocytes by hyaluronan. 1936 Mar 30