J. Muntane et al., TNF-alpha but not IL-1 alpha is correlated with PGE(1)-dependent protection against acute D-galactosamine-induced liver injury, CAN J GASTR, 14(3), 2000, pp. 175-180
BACKGROUND: Prostaglandin E-1 (PGE(1)) treatment of humans and rodents duri
ng acute hepatic failure ameliorates different parameters of hepatic dysfun
ction.
PURPOSE: To investigate whether prevention of acute liver injury induced by
D-galactosamine (D-GalN) with preadministration of PGE(1) is correlated wi
th a change in the concentration of two proinflammatory cytokines, as tumou
r necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 alpha, and/or ni
trite+nitrate (NOx), as nitric oxide-related end products in serum.
RESULTS: D-GalN significantly increased alanine aminotransferase (ALT) and
TNF-alpha concentration in serum 5 and 10 mins, respectively, after treatme
nt compared with the control group (P less than or equal to 0.05). D-GalN d
id not change the IL-1 alpha concentration at any time during the study. Pr
eadministration of PGE(1) to D-GalN-treated rats significantly reduced the
ALT content and increased significantly the TNF-alpha concentration in seru
m 1, 2.5, 5 and 10 mins after D-GalN treatment compared with the D-GalN gro
up (P less than or equal to 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 inc
reased TNF-alpha release. Preadministration of PGE1 to D-GalN-treated rats
exerted a priming effect on inflammatory cells to release enhanced levels o
f TNF-alpha but not IL-1 alpha. These findings indicate that stimulation of
TNF-alpha release may be involved in the acute D-GalN-induced liver injury
and also in PGE(1) protection from hepatotoxicity in clinical and experime
ntal studies.