title: Vitamin D3protects against prednisolone-induced liver injury associated with the impairment of the hepatic NF-κB/iNOS/NO pathway.
abstract: The study was carried out to define whether prednisolone-induced damage to hepatic cells is accompanied by excessive nitric oxide (NO) levels associated with nuclear factor kappa B (NF-κB)/inducible NO synthase (iNOS) activation and evaluate the efficacy of the treatment with vitamin D3. Histopathological examination, activities of liver transaminases (alanine aminotransferase and aspartate aminotransferase), and cell death assays consistently showed that prednisolone (5 mg/kg body weight, 30 days) induces chronic liver injury in female Wistar rats. Specifically, increased hepatocellular necrosis and caspase-3-dependent apoptosis were observed. Prednisolone enhanced iNOS protein expression, NO generation, and tyrosine nitration in liver cells. Despite unchanged hepatic level of the NF-κB/p65 protein, prednisolone increased inhibitory κB-α (IκB-α) degradation, nuclear translocation, and phosphorylation of NF-κB/p65 at Ser311, indicating that NF-κB activation can be involved in the induction of iNOS/NO. All changes were associated with a 2.9-fold decrease in the serum content of 25-hydroxyvitamin D3and significant reduction of hepatic vitamin D3receptor (VDR) expression that points reliably to vitamin D3deficiency and failures in VDR signaling. Vitamin D3co-administration (100 IU/rat, 30 days) prevented glucocorticoid-evoked abnormalities in hepatic tissue. In conclusion, prednisolone-induced liver disturbances were associated with the impairment of NF-κB/iNOS/NO responses that can be ameliorated by vitamin D3treatment through VDR-mediated mechanisms.
authors.affiliation: O.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 01601, Leontovich str., 9, Kyiv, Ukraine.|O.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 01601, Leontovich str., 9, Kyiv, Ukraine.
authors.forename: Olha
authors.initials: O
authors.lastname: Lisakovska
authors.affiliation: O.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 01601, Leontovich str., 9, Kyiv, Ukraine.|O.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 01601, Leontovich str., 9, Kyiv, Ukraine.
authors.forename: Ihor
authors.initials: I
authors.lastname: Shymanskyy
authors.affiliation: O.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 01601, Leontovich str., 9, Kyiv, Ukraine.|O.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 01601, Leontovich str., 9, Kyiv, Ukraine.
authors.forename: Anna
authors.initials: A
authors.lastname: Mazanova
authors.affiliation: O.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 01601, Leontovich str., 9, Kyiv, Ukraine.|O.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 01601, Leontovich str., 9, Kyiv, Ukraine.
authors.forename: Anna
authors.initials: A
authors.lastname: Khomenko
authors.affiliation: O.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 01601, Leontovich str., 9, Kyiv, Ukraine.|O.V. Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 01601, Leontovich str., 9, Kyiv, Ukraine.
authors.forename: Mykola
authors.initials: M
authors.lastname: Veliky
mesh_terms: D000410:Alanine Transaminase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002762:Cholecalciferol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011239:Prednisolone / Q000037:antagonists & inhibitors / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D020011:Protective Agents; D018167:Receptors, Calcitriol; D051996:Transcription Factor RelA; D002762:Cholecalciferol; D009569:Nitric Oxide; D011239:Prednisolone; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: facteur nucléaire kappa B; inducible nitric oxide synthase; nitric oxide; nuclear factor kappa B; oxyde nitrique; prednisolone; synthase d’oxyde nitrique inductible; vitamin D3; vitamine D3