title: Inducible Nitric Oxide Synthase Expression in Liver Injury: Liver Protective Effects on Primary Rat Hepatocytes.
abstract: OBJECTIVE
  Following injury to the liver, liver cells, including Kupffer cells and hepatocytes express inducible nitric oxide synthase (iNOS), followed by the production of excess levels of nitric oxide (NO). NO produced by iNOS has been found to contribute to liver injury. Treatment of primary cultures of rat hepatocytes with the proinflammatory cytokine interleukin (IL)-1β stimulated iNOS expression and NO production. Experiments with this in vitro hepatocyte model of liver injury and with in vivo animal models of liver injury have demonstrated that drugs showing a liver-protective effect in vivo also inhibited the induction of iNOS expression and NO production both in vivo and in vitro. Thus, in this in vitro hepatocyte model, the prevention of iNOS expression and NO production are considered indicators of liver protection.
  
  
  CONCLUSIONS
  This review describes a simple in vitro liver injury model, consisting of IL-1β-stimulated cultured hepatocytes, and methods used to analyze the mechanisms of action of drugs that inhibit iNOS expression. This in vitro hepatocyte model may be used to assess the liver-protective effects of pharmaceutical agents, herbal medicines, and certain types of foods.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kaibori
authors.affiliation: Department of Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka 573-1010, Japan. okumura@hirakata.kmu.ac.jp.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Okumura
authors.forename: Kenji
authors.initials: K
authors.lastname: Sato
authors.forename: Mikio
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Kon
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D019610:Cytoprotection; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D053583:Interleukin-1beta / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D020011:Protective Agents / Q000494:pharmacology*; D017208:Rats, Wistar
chemical_list: D053583:Interleukin-1beta; D020011:Protective Agents; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat