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Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes

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World Journal of Gastroenterology 2001年第3期7卷 331-334页

作者： Guo Liang Zhang Ye Hong Wang Hui Ling Teng Zhi Bin Lin Department of Pharmacology,School of Basic Medical Sciences,Beijing University,Beijiog 100083,ChinaDr.Guo Liang Zhang graduated from Xinxiang Medical College in 1982,got Ph.D.at Nagoya City University Medical School,Japan in 1994,finished postdoctoral research at Beijing Medical Univcrsity in 1996,now an associate professor of pharmacology,specialized in hepatic pharmacology,having 15 papers published. Department of Pharmacology School of Basic Medical Sciences Beijing University Beijing 100083 China. yuankui@***

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-L-arginine (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 24h. 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 iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x 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 x 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.

关键词： Animals Antineoplastic Agents Cells, Cultured Comparative Study Cyclic GMP Cytokines Dactinomycin Dexamethasone Enzyme Inhibitors Glucocorticoids Guanidines Hepatocytes Interferon Type II Interleukin-1 Lipopolysaccharides Male NG-nitroarginine Methyl Ester Nitric Oxide Nitric Oxide Synthase inhibitors nitroarginine Protein Synthesis Inhibitors Rats Rats, Wistar Research Support, Non-U.S. Gov't Tumor Necrosis Factor-alpha

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Danlou Fang(丹蒌方)reduces microvascular obstruction through the endothelial/inducible nitric oxide synthase pathway in a rat model

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Journal of Traditional Chinese Medicine 2021年第2期41卷 246-253页

作者： DAI Xiangdong CHEN Rui CHEN Ting YAN Haifeng WANG Yanyan ZHOU Kun ZHANG Xiting WANG Yi Institute of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China

OBJECTIVE:To investigate the efficacy of the Danlou Fang(DL)Traditional Chinese Medicine formula on microvascular obstruction(no-reflow)through the endothelial/inducible nitric oxide synthase(eNOS/iNOS)pathway in a rat ***:Sprague-Dawley rats were subjected to 60 min of coronary artery occlusion(or sham procedure)followed by 2 h of reperfusion and were then divided into treatment groups:sham,model,DL(500 mg/kg),DL(500 mg/kg)+eNOS inhibitor L-nitroarginine(L-NNA;7.5 mg/kg),and sodium nitroprusside(SNP;0.5 mg/kg).There were 16 per *** of no-reflow were determined by thioflavin S staining of heart *** function was assessed by *** enzymes and antioxidants in serum were measured and *** relative protein expression levels of eNOS and iNOS were determined by western ***:DL had a myocardial protective effect on myocardial reperfusion and reduced the area of *** serum levels of creatine kinase(CK),myocardial CK isoenzyme CK-MB,and lactate dehydrogenase were significantly lower in the DL group than in the model(P<0.05).DL treatment also decreased the serum content of malondialdehyde and reactive oxygen species(ROS),increased the activity of superoxide dismutase and nitric oxide,and promoted eNOS expression(P<0.05)while lowering iNOS ***:DL reduced the area of no-reflow and had a myocardial protective effect that may be associated with the eNOS/iNOS pathway.

关键词： no-reflow phenomenon nitric oxide synthase creatine kinase nitroarginine reactive oxygen species Danlou Fang

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