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  • Title: Tolerance against tumor necrosis factor alpha (TNF)-induced hepatotoxicity in mice: the role of nitric oxide.
    Author: Bohlinger I, Leist M, Barsig J, Uhlig S, Tiegs G, Wendel A.
    Journal: Toxicol Lett; 1995 Dec; 82-83():227-31. PubMed ID: 8597057.
    Abstract:
    D-Galactosamine-sensitized mice challenged with tumor necrosis factor alpha (TNF) developed severe apoptotic and secondary necrotic liver injury 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 nitrite/nitrate in serum and rendered mice insensitive towards TNF toxicity. Pharmacological doses of the nitric oxide (NO) donor sodium nitroprusside (SNP) also conferred complete protection against TNF toxicity, suggesting a possible link between IL-1- and NO-induced protection. However, NO-synthesis inhibition by NG-monomethyl-L-arginine failed to abrogate IL-1-induced tolerance against TNF toxicity. We conclude that IL-1 and NO protect against TNF-induced liver injury through distinct pathways.
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