I. Bohlinger et al., TOLERANCE AGAINST TUMOR-NECROSIS-FACTOR ALPHA(TNF)-INDUCED HEPATOTOXICITY IN MICE - THE ROLE OF NITRIC-OXIDE, Toxicology letters, 82-3, 1995, pp. 227-231
D-Galactosamine-sensitized mice challenged with tumor necrosis factor
alpha (TNF) developed severe apoptotic and secondary necrotic liver in
jury as assessed by histology, measurement of cytosolic DNA fragments
and determination of liver-specific enzymes in plasma. Pretreatment of
mice with interleukin-1 beta (IL-1) resulted in elevated levels of ni
trite/nitrate in serum and rendered mice insensitive towards TNF toxic
ity. Pharmacological doses of the nitric oxide (NO) donor sodium nitro
prusside (SNP) also conferred complete protection against TNF toxicity
, suggesting a possible link between IL-1- and NO-induced protection.
However? NO-synthesis inhibition by N-G-monomethyl-L-arginine failed t
o abrogate IL-l-induced tolerance against TNF toxicity. We conclude th
at IL-1 and NO protect against TNF-induced liver injury through distin
ct pathways.