title: Bone marrow mononuclear cell transplantation improves mitochondrial bioenergetics in the liver of cholestatic rats.
abstract: Mitochondrial dysfunction has been associated with liver cholestatis. Toxic bile salt accumulation leads to chronic injury with mitochondrial damage, ROS increase and apoptosis, resulting in liver dysfunction. This study aimed to analyze mitochondrial bioenergetics in rats with hepatic fibrosis induced by bile duct ligation (BDL) after BMMNC transplantation. Livers were collected from normal rats, fibrotic rats after 14 and 21 days of BDL (F14d and F21d) and rats that received BMMNC at 14 days of BDL, analyzed after 7 days. F21d demonstrated increased collagen I content and consequently decrease after BMMNC transplantation. Both F14d and F21d had significantly reduced mitochondrial oxidation capacity and increased mitochondrial uncoupling, which were restored to levels similar to those of normal group after BMMNC transplantation. In addition, F21d had a significantly increase of UCP2, and reduced PGC-1α content. However, after BMMNC transplantation both proteins returned to levels similar to normal group. Moreover, F14d had a significantly increase in 4-HNE content compared to normal group, but after BMMNC transplantation 4-HNE content significantly reduced, suggesting oxidative stress reduction. Therefore, BMMNC transplantation has a positive effect on hepatic mitochondrial bioenergetics of cholestatic rats, increasing oxidative capacity and reducing oxidative stress, which, in turn, contribute to liver function recover.
authors.affiliation: Laboratory of Stem Cell Research, Department of Histology and Embryology, Institute of Biology, State University of Rio de Janeiro, UERJ, Av. Prof. Manoel de Abreu 444, 3° andar, 20550-170 Rio de Janeiro, Brazil.
authors.forename: Daniela Caldas
authors.initials: DC
authors.lastname: de Andrade
authors.affiliation: Laboratory of Stem Cell Research, Department of Histology and Embryology, Institute of Biology, State University of Rio de Janeiro, UERJ, Av. Prof. Manoel de Abreu 444, 3° andar, 20550-170 Rio de Janeiro, Brazil.
authors.forename: Simone Nunes
authors.initials: SN
authors.lastname: de Carvalho
authors.affiliation: Laboratory of Stem Cell Research, Department of Histology and Embryology, Institute of Biology, State University of Rio de Janeiro, UERJ, Av. Prof. Manoel de Abreu 444, 3° andar, 20550-170 Rio de Janeiro, Brazil.
authors.forename: Daphne
authors.initials: D
authors.lastname: Pinheiro
authors.affiliation: Laboratory of Stem Cell Research, Department of Histology and Embryology, Institute of Biology, State University of Rio de Janeiro, UERJ, Av. Prof. Manoel de Abreu 444, 3° andar, 20550-170 Rio de Janeiro, Brazil.
authors.forename: Alessandra Alves
authors.initials: AA
authors.lastname: Thole
authors.affiliation: Labotatory of Nutrition and Development Physiology, Department of Physiological Sciences, Institute of Biology, State University of Rio de Janeiro, UERJ, Av. Prof. Manoel de Abreu 444, 5° andar, 20550-170 Rio de Janeiro, Brazil.
authors.forename: Anibal Sanchez
authors.initials: AS
authors.lastname: Moura
authors.affiliation: Laboratory of Stem Cell Research, Department of Histology and Embryology, Institute of Biology, State University of Rio de Janeiro, UERJ, Av. Prof. Manoel de Abreu 444, 3° andar, 20550-170 Rio de Janeiro, Brazil.
authors.forename: Lais
authors.initials: L
authors.lastname: de Carvalho
authors.affiliation: Laboratory of Stem Cell Research, Department of Histology and Embryology, Institute of Biology, State University of Rio de Janeiro, UERJ, Av. Prof. Manoel de Abreu 444, 3° andar, 20550-170 Rio de Janeiro, Brazil. Electronic address: cortez.erika@gmail.com.
authors.forename: Erika Afonso Costa
authors.initials: EA
authors.lastname: Cortez
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D002779:Cholestasis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004734:Energy Metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
keywords: Bone marrow mononuclear cells; Cholestasis; Liver fibrosis; Mitochondria; Mitochondrial bioenergetics