title: [Effect of inducible nitric oxide on intracellular homeostasis of hepatocytes].
abstract: OBJECTIVE
  To investigate the effects of inducible nitric oxide (NO) and exogenous NO on the intracellular homeostasis of the hepatocytes.
  
  
  METHODS
  Endogenous NO was induced by combined action of lipopolysaccharide (LPS) and cytokines in cultured rat hepatocytes, and exogenous NO was supplied by sodium nitroprusside (SNP) to stimulate the hepatocytes. The changes in intracellular malondialdehyde (MDA), reduced glutathione(GSH) and free calcium ([Ca2+]i) were observed.
  
  
  RESULTS
  substantial increase by 7.97 times in intracellular MDA level and a decrease by 57.9% in GSH occurred in the hepatocytes after the cells had been incubated with LPS and cytokines for 24 h, which were reversed by 43.5% and 98.4% respectively by treatment with N(G)-monomethyl-L-arginine (NMMA), a competitive nitric oxide synthase (NOS) inhibitor. Verapamil significantly reduced both endogenous NO production and oxidative stress, while the effect of A23187 was not conspicuous. Incubation with chlorpromazine and Vitamine E (VitE), however, did not result in decreased release of NO by LPS- and cytokines-induced hepatocytes. After SNP exposure of the hepatocytes, the oxidative status was reversibly enhanced in a time-dependent manner. Short exposure to SNP led to a concentration-dependent inhibition of the rapid and transient increase in free calcium induced by K(+) depolarization and hepatopoietin-coupled calcium mobilization.
  
  
  CONCLUSIONS
  Inducible NO may initiate and play a key role in the latter stages of metabolic and functional stress responses of hepatocytes against endotoxin and cytokines, when the reduction occurs in the capacity of NO to independently mediate lipid peroxidation and counteract oxidation. The inhibitory effect of NO on [Ca2+]i mobilization may be an important autoregulatory mechanism by means of negative feedback on protein kinase C-associated NOS induction.
authors.affiliation: Department of Laboratory Diagnosis, Nanfang Hospital, First Military Medical University, Guangzhou 510515, China.
authors.forename: Xi-Feng
authors.initials: XF
authors.lastname: Tang
authors.forename: Dong-Yao
authors.initials: DY
authors.lastname: Zhou
authors.forename: Ge-Fei
authors.initials: GF
authors.lastname: Kang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D015227:Lipid Peroxidation / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats
chemical_list: D008070:Lipopolysaccharides; D009599:Nitroprusside; D009569:Nitric Oxide; D008315:Malondialdehyde; D005978:Glutathione; D002118:Calcium