title: Role of nitric oxide in D-galactosamine-induced cell death and its protection by PGE1 in cultured hepatocytes.
abstract: Prostaglandin E(1) (PGE(1)) reduces cell death in experimental and clinical manifestations of liver dysfunction. Nitric oxide (NO) has been shown to exert a protective or noxious effect in different experimental models of liver injury. The aim of the present study was to investigate the role of NO during PGE(1) protection against D-galactosamine (D-GalN) citotoxicity in cultured hepatocytes. PGE(1) was preadministered to D-GalN-treated hepatocytes. The role of NO in our system was assessed by iNOS inhibition and a NO donor. Different parameters related to apoptosis and necrosis, NO production such as nitrite+nitrate (NO(x)) release, iNOS expression, and NF-kappaB activation in hepatocytes were evaluated. The inhibition of iNOS reduced apoptosis induced by D-GalN in hepatocytes. PGE(1) protection against D-GalN injury was associated with its capacity to reduce iNOS expression and NO production induced by D-GalN. Nevertheless, iNOS inhibition showed that protection by PGE(1) was also mediated by NO. Low concentrations of a NO donor reduced D-GalN injury with a decrease in the extracellular NO(x) concentration. High concentrations of the NO donor enhanced NO(x) concentration and increased cell death by D-GalN. The present study suggests that low NO production induced by PGE(1) preadministration reduces D-GalN-induced cell death through its capacity to reduce iNOS expression and NO production caused by the hepatotoxin.
authors.affiliation: Unidad de Investigación, Servicio Aparato Digestivo, Hospital Universitario Reina Sofi;a, Av. Menéndez Pidal s/n, E-14004, Córdoba, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Siendones
authors.forename: Dalia
authors.initials: D
authors.lastname: Fouad
authors.forename: Amira Mohamed Kamal ElSaid
authors.initials: AM
authors.lastname: Abou-Elella
authors.forename: Ana
authors.initials: A
authors.lastname: Quintero
authors.forename: Pilar
authors.initials: P
authors.lastname: Barrera
authors.forename: Jordi
authors.initials: J
authors.lastname: Muntané
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000032:analysis / Q000096:biosynthesis; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D003627:Data Interpretation, Statistical; D024202:Electrophoretic Mobility Shift Assay; D005688:Galactosamine / Q000037:antagonists & inhibitors; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051017:Apoptosis Regulatory Proteins; C091572:DAP protein, human; D016328:NF-kappa B; D020030:Nitric Oxide Donors; D011458:Prostaglandins E; D011506:Proteins; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D005688:Galactosamine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D010396:Penicillamine