title: Induction of xanthine oxidase activity, endoplasmic reticulum stress and caspase activation by sodium metabisulfite in rat liver and their attenuation by Ghrelin.
abstract: Sodium metabisulfite is used as a preservative in many food preparations but can oxidize to sulfite radicals initiating molecular oxidation. Ghrelin is a peptide hormone primarily produced in the stomach and has anti-inflammatory and anti-oxidant effects on gastrointestinal and cardiovascular systems. This study was performed to elucidate the effect of ghrelin on sulfite-induced endoplasmic reticulum (ER) stress and caspase activation in rat peripheral organs. Xanthine oxidase (XO), xanthine dehydrogenase (XDH) enzyme activities, ER stress markers [phosphorylated PKR-like ER kinase (pPERK); C/EBP-homologous protein (CHOP)], caspase-3, -8, -9 activities, nuclear factor kappa-B (NF-κB) levels were determined in liver, heart and kidney of rats treated with sodium metabisulfite and/or ghrelin for 5 weeks. Sodium metabisulfite treatment significantly elevated XO activity, induced expression of GRP78, CHOP and increased caspase-3, -8 and -9 activities in liver but had no significant effect in heart and kidney. Ghrelin treatment decreased XO activity to baseline levels and attenuated ER stress and caspase activation in liver tissue of sodium metabisulfite treated rats. In conclusion, metabolism of sodium metabisulfite in liver tissue increased XO activity, induced ER stress and caused caspase activation which was attenuated by ghrelin treatment. Ghrelin's hepatoprotective effect could be through modulation of XO activity.
authors.affiliation: Vocational School of Health Services, Akdeniz University, Antalya 07070, Turkey.
authors.forename: Sevim
authors.initials: S
authors.lastname: Ercan
authors.affiliation: Department of Biophysics, Akdeniz University Medical School, Antalya 07070, Turkey.
authors.forename: Ceren
authors.initials: C
authors.lastname: Kencebay
authors.affiliation: Department of Biophysics, Akdeniz University Medical School, Antalya 07070, Turkey.
authors.forename: Goksun
authors.initials: G
authors.lastname: Basaranlar
authors.affiliation: Department of Biophysics, Akdeniz University Medical School, Antalya 07070, Turkey.
authors.forename: Narin
authors.initials: N
authors.lastname: Derin
authors.affiliation: Department of Medical Biochemistry, Akdeniz University Medical School, Antalya 07070, Turkey. Electronic address: mutayaslan@akdeniz.edu.tr.
authors.forename: Mutay
authors.initials: M
authors.lastname: Aslan
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D054439:Ghrelin / Q000008:administration & dosage*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013447:Sulfites / Q000008:administration & dosage* / Q000009:adverse effects*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D054439:Ghrelin; D006360:Heat-Shock Proteins; D016328:NF-kappa B; D013447:Sulfites; D051742:Transcription Factor CHOP; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C005200:sodium metabisulfite; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat
keywords: Endoplasmic reticulum stress; Ghrelin; Sodium metabisulfite; Xanthine oxidase