s-nitro-n-acetylpenicillamine and Liver-Diseases

To investigate the role of nitric oxide (NO) in the liver injury induced by delayed-type hypersensitivity to picryl chloride (PCl-DTH).. Liver injury was induced in mice by PCl-DTH. NO production was examined using the Griess reagent. Isolated hepatocytes (HC) and nonparenchymal cells (NPC) were used.. NO production in both serum and liver tissue reached a peak at 36 h after the elicitation of liver injury. The in vitro NO production was only observed by NPC or HC isolated at 24 h after the injury. Co-stimulation of IFN-gamma and TNF-alpha significantly triggered the HC and NPC isolated at 0 h to produce NO. As NO synthase inhibitors, Nomega-Nitro-L-Arginine exacerbated the liver injury in mice and NG-Monomethyl-L-Arginine enhanced the hepatotoxicity of IFN-gamma and TNF-alpha in vitro. In contrast, NO producer, S-nitroso-N-acetylpenicillamine dose-dependently inhibited the hepatotoxicity of NPC.. NO may be produced by HC and NPC under the co-stimulation of IFN-gamma and TNF-alpha, and may play an important role for alleviating the liver injury.

Topics: Animals; Cells, Cultured; Chemical and Drug Induced Liver Injury; Enzyme Inhibitors; Female; Hepatocytes; Hypersensitivity, Delayed; Interferon-gamma; Liver; Liver Diseases; Male; Mice; Mice, Inbred BALB C; Nitric Oxide; Nitric Oxide Donors; omega-N-Methylarginine; Penicillamine; Picryl Chloride; Time Factors; Tumor Necrosis Factor-alpha