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Liver disease
TNF-α dependent production of inducible nitric oxide is involved in PGE1 protection against acute liver injury
  1. J Muntanéa,
  2. F J Rodrígueza,
  3. O Segadoa,
  4. A Quinteroa,
  5. J M Lozanoa,
  6. E Siendonesa,
  7. C A Pedrazaa,
  8. M Delgadoa,
  9. F O'Valleb,
  10. R Garcíab,
  11. J L Monteroa,
  12. M De la Mataa,
  13. G Miñoa
  1. aServicio Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España, bDepartamento Anatomía Patológica, Facultad de Medicina, Granada, España
  1. Dr J Muntané Relat, Unidad de Investigación, Servicio Aparato Digestivo, Hospital Universitario Reina Sofía, Av. Menendez Pidal s/n, 14004 Córdoba, Spain. Email. jmuntane{at}sofia.hrs.sas.cica.es

Abstract

BACKGROUND Tumour necrosis factor α (TNF-α) 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 E1 (PGE1) was accompanied by an increase in TNF-α and nitrite/nitrate in serum.

AIMS The aim of the present study was to evaluate the role of TNF-α and nitric oxide during protection by PGE1 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. PGE1 was administered 30 minutes before D-GalN. Inducible nitric oxide synthase (iNOS) was inhibited by methylisothiourea (MT), and TNF-α concentration in serum was lowered by administration of anti-TNF-α antibodies. Liver injury was evaluated by alanine aminotransferase activity in serum, and histological examination and DNA fragmentation in liver. TNF-α and nitrite/nitrate concentrations were determined in serum. Expression of TNF-α and iNOS was also assessed in liver sections.

RESULTS PGE1decreased liver injury and increased TNF-α and nitrite/nitrate concentrations in serum of rats treated with D-GalN. PGE1protection was related to enhanced expression of TNF-α and iNOS in hepatocytes. Administration of anti-TNF-α antibodies or MT blocked the protection by PGE1 of liver injury induced by D-GalN.

CONCLUSIONS This study suggests that prior administration of PGE1 to D-GalN treated animals enhanced expression of TNF-α and iNOS in hepatocytes, and that this was causally related to protection by PGE1against D-GalN induced liver injury.

  • tumour necrosis factor α
  • nitric oxide
  • prostaglandin E1
  • methylisothiourea
  • d-galactosamine
  • liver injury

  • Abbreviations used in this paper

    TNF-α
    tumour necrosis factor α
    D-GalN
    d-galactosamine
    PGE1
    prostaglandin E1
    iNOS
    inducible nitric oxide synthase
    cNOS
    constitutive nitric oxide synthase
    MT
    methylisothiourea
    ALT
    alanine aminotransferase
    PBS
    phosphate buffered solution

    • https://doi.org/10.1136/gut.47.4.553

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    • Abbreviations used in this paper

      TNF-α
      tumour necrosis factor α
      D-GalN
      d-galactosamine
      PGE1
      prostaglandin E1
      iNOS
      inducible nitric oxide synthase
      cNOS
      constitutive nitric oxide synthase
      MT
      methylisothiourea
      ALT
      alanine aminotransferase
      PBS
      phosphate buffered solution
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