TNF-α dependent production of inducible nitric oxide is involved in PGE1 protection against acute liver injury. Issue 4 (1st October 2000)

• Record Type: Journal Article
• Authors: Muntané, J; Rodríguez, F J; Segado, O; Quintero, A; Lozano, J M; Siendones, E; Pedraza, C A; Delgado, M; O'Valle, F; García, R; Montero, J L; De la Mata, M; Miño, G
• Is Part Of: Gut. Volume 47:Issue 4(2000)
• Page Start: 553
• Page End: 562
• Publication Date: 2000-10-01
• Subjects: tumour necrosis factor α -- nitric oxide -- prostaglandin E1 -- methylisothiourea -- d-galactosamine -- liver injury; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.47.4.553
• Languages: English
• ISSNs: 0017-5749

Abstract

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: PGE1 decreased liver injury and increased TNF-α and nitrite/nitrate concentrations in serum of rats treated with D-GalN. PGE1 protection 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 PGE1 against D-GalN induced liver injury.