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Canadian Journal of Gastroenterology
Volume 14 (2000), Issue 3, Pages 175-180
Original Article

TNF-alpha but not IL-1alpha are Correlated with PGE1-Dependent Protection Against Acute D-Galactosamine-Induced Liver Injury

J Muntané, JL Montero, JM Lozano, A Miranda-Vizuete, M de la Mata, and G Miño

Servicio Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, Spain

Received 13 March 1998; Revised 13 January 1999

Copyright © 2000 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


BACKGROUND: Prostaglandin E1 (PGE1) treatment of humans and rodents during acute hepatic failure ameliorates different parameters of hepatic dysfunction.

PURPOSE: To investigate whether prevention of acute liver injury induced by D-galactosamine (D-GalN) with preadministration of PGE1 is correlated with a change in the concentration of two proinflammatory cytokines, as tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-1α, and/or nitrite+nitrate (NOx), as nitric oxide-related end products in serum.

RESULTS: D-GalN significantly increased alanine aminotransferase (ALT) and TNF- αconcentration in serum 5 and 10 mins, respectively, after treatment compared with the control group (P≤0.05). D-GalN did not change the IL-1α concentration at any time during the study. Preadministration of PGE1 to D-GalN-treated rats significantly reduced the ALT content and increased significantly the TNF-α concentration in serum 1, 2.5, 5 and 10 mins after D-GalN treatment compared with the D-GalN group (P≤0.05). Nitric oxide was not involved in either the toxic effect due to D-GalN or the protection observed with PGE1 against D-GalN toxicity.

CONCLUSIONS: Acute liver injury induced by D-GalN is correlated with an increased TNF-α release. Preadministration of PGE1 to D-GalN-treated rats exerted a priming effect on inflammatory cells to release enhanced levels of TNF-α but not IL-1α. These findings indicate that stimulation of TNF-α release may be involved in the acute D-GalN-induced liver injury and also in PGE1 protection from hepatotoxicity in clinical and experimental studies.