IR@PKUHSC  > 北京大学基础医学院  > 药理学系
学科主题基础医学
Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes
Zhang, GL; Wang, YH; Teng, HL; Bin Lin, Z
刊名WORLD JOURNAL OF GASTROENTEROLOGY
2001-06-01
7期:3页:331-334
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Gastroenterology & Hepatology
研究领域[WOS]Gastroenterology & Hepatology
关键词[WOS]NF-KAPPA-B ; SYNTHASE EXPRESSION ; LIVER-DAMAGE ; ACTIVATION ; INHIBITION ; APOPTOSIS ; CELLS ; LIPOPOLYSACCHARIDE ; MACROPHAGES ; INDUCTION
英文摘要

AIM To study the effects of aminoguanidine (AG) and two L-arginine analogues N-omega-nitro-L-arginine methyl ester (L-NAME) and N-omega-nitro-Larginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action.

METHODS Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24 h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG (53.7%, P <0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone ( DEX) and MOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG (0.1 mmol.L-1) and ActD (0.2 ng.L-1) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol.L-1) under similar stimuli conditions (P <0.01).

CONCLUSION AG is a potent selective inhibitor of inducible isoform of NOS, and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.

语种英语
WOS记录号WOS:000170371000007
Citation statistics
Cited Times:28[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66474
Collection北京大学基础医学院_药理学系
作者单位Beijing Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing 100083, Peoples R China
Recommended Citation
GB/T 7714
Zhang, GL,Wang, YH,Teng, HL,et al. Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes[J]. WORLD JOURNAL OF GASTROENTEROLOGY,2001,7(3):331-334.
APA Zhang, GL,Wang, YH,Teng, HL,&Bin Lin, Z.(2001).Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes.WORLD JOURNAL OF GASTROENTEROLOGY,7(3),331-334.
MLA Zhang, GL,et al."Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes".WORLD JOURNAL OF GASTROENTEROLOGY 7.3(2001):331-334.
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