Protective involvement of nitric oxide in the liver injury induced by delayed-type hypersensitivity to picryl chloride

Objective and Design: To investigate the role of nitric oxide (NO) in the liver injury induced by delayed-type hypersensitivity to picryl chloride (PCl-DTH).¶Materials and Methods: 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.¶Results: 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-γ and TNF-α significantly triggered the HC and NPC isolated at 0 h to produce NO. As NO synthase inhibitors, Nω-Nitro-L-Arginine exacerbated the liver injury in mice and NG-Monomethyl-L-Arginine enhanced the hepatotoxicity of IFN-γ and TNF-α in vitro. In contrast, NO producer, S-nitroso-N-acetylpenicillamine dose-dependently inhibited the hepatotoxicity of NPC.¶Conclusions: NO may be produced by HC and NPC under the co-stimulation of IFN-γ and TNF-α, and may play an important role for alleviating the liver injury.