title: Discontinuous total parenteral nutrition prevents postischemic mitochondrial dysfunction in rat liver.
abstract: Although discontinuous total parenteral nutrition (d-TPN) has recently been favored for clinical use over continuous total parenteral nutrition (c-TPN) to ameliorate liver dysfunction, mechanisms for the protection against postoperative liver dysfunction remain unknown. This study aimed to examine differences in mitochondrial function in d-TPN- and c-TPN-pretreated livers during ischemia-reperfusion. Rat livers pretreated with d-TPN or c-TPN were perfused with Krebs-Ringer buffer and were exposed to 25% low-flow hypoxia followed by reperfusion. Intrahepatic mitochondrial membrane potential (triangle up) and cell viability were assessed by dual-color digital microfluorography using rhodamine 123 (Rh123) and propidium iodide (PI), respectively. In response to hypoxia, livers pretreated with c-TPN, d-TPN, and an ordinary chow diet exhibited a significant triangle up reduction among the entire lobules. Upon reperfusion, the regional triangle up values further decreased in the c-TPN liver, whereas those in the d-TPN-treated or chow-treated livers displayed a rapid recovery toward the control levels. The severity of cell injury did not differ among the groups, showing that the reperfusion-induced triangle up drop in the c-TPN-pretreated liver is not a consequence of cell injury. Differences in the triangle up drop among the groups appear to occur irrespective of those in the glycogen storage, because the livers undergoing d-TPN display a marked triangle up recovery even when reperfused at the end of a fasted state. These results indicate that c-TPN, but not d-TPN, jeopardizes mitochondrial re-energization and suggest that a circadian pattern of the TPN serves as a potentially beneficial strategy to reduce the risk of postischemic mitochondrial dysfunction in the liver.
authors.affiliation: Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Morikawa
authors.forename: M
authors.initials: M
authors.lastname: Suematsu
authors.forename: T
authors.initials: T
authors.lastname: Kyokane
authors.forename: N
authors.initials: N
authors.lastname: Goda
authors.forename: Y
authors.initials: Y
authors.lastname: Kumamoto
authors.forename: T
authors.initials: T
authors.lastname: Okitsu
authors.forename: Y
authors.initials: Y
authors.lastname: Ishimura
authors.forename: M
authors.initials: M
authors.lastname: Kitajima
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D002470:Cell Survival; D005456:Fluorescent Dyes; D006003:Glycogen / Q000378:metabolism; D007425:Intracellular Membranes / Q000502:physiology; D007511:Ischemia / Q000150:complications*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008564:Membrane Potentials; D008930:Mitochondria, Liver / Q000502:physiology* / Q000648:ultrastructure; D009752:Nutritional Status; D010289:Parenteral Nutrition, Total / Q000379:methods*; D010587:Phagocytosis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D020112:Rhodamine 123
chemical_list: D005456:Fluorescent Dyes; D020112:Rhodamine 123; D006003:Glycogen