Mice lacking inducible nitric oxide synthase show strong resistance to anti-Fas antibody-induced fulminant hepatitis.
Although nitric oxide (NO) plays important roles in pathogenesis of various liver diseases, the role of NO in the in vivo mechanism of Fas-mediated fulminant hepatitis is not known well. The effect of anti-Fas antibody (Jo2) on the survival, liver function, and histology was analyzed in wild-type (WT) and inducible NO synthase (iNOS)-deficient (iNOS(-/-)) mice. Upon intravenous injection of a lethal dose of Jo2, WT mice died on fulminant hepatitis within 12h. Under identical conditions, however, iNOS(-/-) mice showed strong resistance to Jo2 and survived without revealing liver injury. In conclusion, these observations suggest that regulation of NO metabolism may have therapeutic potential in the treatment of patients with fulminant hepatitis.
Chang
BaoJun
B
Department of Biochemistry & Molecular Pathology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno, 545-8585, Osaka, Japan.
Nishikawa
Manabu
M
Sato
Eisuke
E
Inoue
Masayasu
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000906:Antibodies / Q000633:toxicity*; D017209:Apoptosis / Q000502:physiology*; D001219:Aspartate Aminotransferases / Q000097:blood; D004272:DNA, Mitochondrial / Q000235:genetics; D003643:Death; D006520:Hepatitis, Animal / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D017093:Liver Failure / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology*
D000906:Antibodies; D004272:DNA, Mitochondrial; D019014:fas Receptor; D009569:Nitric Oxide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase