title: TNF-alpha dependent production of inducible nitric oxide is involved in PGE(1) protection against acute liver injury.
abstract: BACKGROUND
  Tumour necrosis factor alpha (TNF-alpha) and nitric oxide modulate damage in several experimental models of liver injury. We have previously shown that protection against D-galactosamine (D-GalN) induced liver injury by prostaglandin E(1) (PGE(1)) was accompanied by an increase in TNF-alpha and nitrite/nitrate in serum.
  
  
  OBJECTIVE
  The aim of the present study was to evaluate the role of TNF-alpha and nitric oxide during protection by PGE(1) of liver damage induced by D-GalN.
  
  
  METHODS
  Liver injury was induced in male Wistar rats by intraperitoneal injection of 1 g/kg of D-GalN. PGE(1) was administered 30 minutes before D-GalN. Inducible nitric oxide synthase (iNOS) was inhibited by methylisothiourea (MT), and TNF-alpha concentration in serum was lowered by administration of anti-TNF-alpha antibodies. Liver injury was evaluated by alanine aminotransferase activity in serum, and histological examination and DNA fragmentation in liver. TNF-alpha and nitrite/nitrate concentrations were determined in serum. Expression of TNF-alpha and iNOS was also assessed in liver sections.
  
  
  RESULTS
  PGE(1) decreased liver injury and increased TNF-alpha and nitrite/nitrate concentrations in serum of rats treated with D-GalN. PGE(1) protection was related to enhanced expression of TNF-alpha and iNOS in hepatocytes. Administration of anti-TNF-alpha antibodies or MT blocked the protection by PGE(1) of liver injury induced by D-GalN.
  
  
  CONCLUSIONS
  This study suggests that prior administration of PGE(1) to D-GalN treated animals enhanced expression of TNF-alpha and iNOS in hepatocytes, and that this was causally related to protection by PGE(1) against D-GalN induced liver injury.
authors.affiliation: Servicio Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España. jmuntane@sofia.hrs.sas.cica.es
authors.forename: J
authors.initials: J
authors.lastname: Muntané
authors.forename: F J
authors.initials: FJ
authors.lastname: Rodríguez
authors.forename: O
authors.initials: O
authors.lastname: Segado
authors.forename: A
authors.initials: A
authors.lastname: Quintero
authors.forename: J M
authors.initials: JM
authors.lastname: Lozano
authors.forename: E
authors.initials: E
authors.lastname: Siendones
authors.forename: C A
authors.initials: CA
authors.lastname: Pedraza
authors.forename: M
authors.initials: M
authors.lastname: Delgado
authors.forename: F
authors.initials: F
authors.lastname: O'Valle
authors.forename: R
authors.initials: R
authors.lastname: García
authors.forename: J L
authors.initials: JL
authors.lastname: Montero
authors.forename: M
authors.initials: M
authors.lastname: De La Mata
authors.forename: G
authors.initials: G
authors.lastname: Miño
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000527:Alprostadil / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D005688:Galactosamine; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
chemical_list: D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D005688:Galactosamine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000410:Alanine Transaminase; D000527:Alprostadil