title: Riboflavin (vitamin B-2) reduces hepatocellular injury following liver ischaemia and reperfusion in mice.
abstract: Riboflavin has been shown to exhibit anti-inflammatory and antioxidant properties in the settings of experimental sepsis and ischaemia/reperfusion (I/R) injury. We investigated the effect of riboflavin on normothermic liver I/R injury. Mice were submitted to 60 min of ischaemia plus saline or riboflavin treatment (30 μmoles/kg BW) followed by 6 h of reperfusion. Hepatocellular injury was evaluated by aminotransferase levels, reduced glutathione (GSH) content and the histological damage score. Hepatic neutrophil accumulation was assessed using the naphthol method and by measuring myeloperoxidase activity. Hepatic oxidative/nitrosative stress was estimated by immunohistochemistry. Liver endothelial and inducible nitric oxide synthase (eNOS/iNOS) and nitric oxide (NO) amounts were assessed by immunoblotting and a chemiluminescence assay. Riboflavin significantly reduced serum and histological parameters of hepatocellular damage, neutrophil infiltration and oxidative/nitrosative stress. Furthermore, riboflavin infusion partially recovered hepatic GSH reserves and decreased the liver contents of eNOS/iNOS and NO. These data indicate that riboflavin exerts antioxidant and anti-inflammatory effects in the ischaemic liver, protecting hepatocytes against I/R injury. The mechanism of these effects appears to be related to the intrinsic antioxidant potential of riboflavin/dihydroriboflavin and to reduced hepatic expression of eNOS/iNOS and reduced NO levels, culminating in attenuation of oxidative/nitrosative stress and the acute inflammatory response.
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Sheila Cristina
authors.initials: SC
authors.lastname: Sanches
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Leandra Naira Z
authors.initials: LN
authors.lastname: Ramalho
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Mendes-Braz
authors.affiliation: Department of Pathological Sciences, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Vânia Aparecida
authors.initials: VA
authors.lastname: Terra
authors.affiliation: Department of Pathological Sciences, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Rubens
authors.initials: R
authors.lastname: Cecchini
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Marlei Josiele
authors.initials: MJ
authors.lastname: Augusto
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: framalho@fmrp.usp.br.
authors.forename: Fernando Silva
authors.initials: FS
authors.lastname: Ramalho
mesh_terms: D000818:Animals; D007511:Ischemia / Q000473:pathology*; D008107:Liver Diseases / Q000150:complications* / Q000473:pathology; D051379:Mice; D015424:Reperfusion; D012256:Riboflavin / Q000494:pharmacology*
chemical_list: D012256:Riboflavin
keywords: Inflammation; Ischaemia/reperfusion; Nitric oxide; Oxidative stress; Riboflavin