Protective involvement of nitric oxide in the liver injury induced by delayed-type hypersensitivity to picryl chloride.
OBJECTIVE
To investigate the role of nitric oxide (NO) in the liver injury induced by delayed-type hypersensitivity to picryl chloride (PCl-DTH).


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-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.


CONCLUSIONS
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.
Cao
J
J
Department of Pharmacology for Chinese Materia Medica, China Pharmaceutical University, Nanjing.
Xu
Q
Q
Koda
A
A
D000818:Animals; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000139:chemically induced* / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008107:Liver Diseases / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010853:Picryl Chloride / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D010396:Penicillamine; D010853:Picryl Chloride