title: Ultrastructural zonal heterogeneity of hepatocytes and mitochondria within the hepatic acinus during liver regeneration after partial hepatectomy.
abstract: BACKGROUND
  Partial hepatectomy (70%) induces cell proliferation until the original mass of the liver is restored. In the first 24 h after partial hepatectomy, drastic changes in the metabolism of the remaining liver have been shown to occur. To evaluate changes in hepatocyte ultrastructure within the hepatic acinus during the liver regenerative process, we investigated, by light and electron microscopy observations on specimens taken 0 h, 24 h and 96 h after partial hepatectomy, the hepatocyte structure and ultrastructure in the periportal and pericentral area of the hepatic acinus, with a particular emphasis on mitochondria ultrastructure. Moreover, some biochemical events that could affect the mitochondria ultrastructure and function were investigated.
  
  
  RESULTS
  We found that, 24 h after partial hepatectomy, mitochondria with altered ultrastructure were preferentially localized in the periportal area. Periportal hepatocytes showed also an increase in the number of peroxisomes, free ribosomes, lysosomes and autophagosomes. Altered mitochondria showed swelling, an ultrastructural index of increased membrane permeability, a reduction in the number of cristae, and a rarefied, often vacuoled, matrix. Consistently, an increase in the mitochondrial oxidized/reduced glutathione ratio was found as well as calcium release from mitochondria in a manner inhibited by cyclosporin A. Interestingly, light and electron microscopy analysis showed that the hepatocytes in the periportal area were the cells with the major structural attributes to proliferate. At 96 h after partial hepatectomy, the preferential zonation of altered mitochondria was lost and the normal mitochondrial membrane permeability properties were restored.
  
  
  CONCLUSIONS
  We suggest that 24 h after partial hepatectomy, a preferential zonation of altered mitochondria in the periportal hepatocytes could be involved in the changes of metabolic and functional heterogeneity of the hepatocytes within the hepatic acinus during the regenerative process.
authors.affiliation: Department of Zoology, Laboratory of Histology and Comparative Anatomy, University of Bari, Via Amendola 165/A, 70126 Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Ferri
authors.forename: Loredana
authors.initials: L
authors.lastname: Moro
authors.forename: Maria
authors.initials: M
authors.lastname: Mastrodonato
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Capuano
authors.forename: Ersilia
authors.initials: E
authors.lastname: Marra
authors.forename: Giuseppa Esterina
authors.initials: GE
authors.lastname: Liquori
authors.forename: Margherita
authors.initials: M
authors.lastname: Greco
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006498:Hepatectomy; D022781:Hepatocytes / Q000648:ultrastructure*; D007425:Intracellular Membranes / Q000502:physiology; D008099:Liver / Q000648:ultrastructure*; D008115:Liver Regeneration; D008297:Male; D008853:Microscopy; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000648:ultrastructure*; D008933:Mitochondrial Swelling; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D002118:Calcium; D019803:Glutathione Disulfide