title: Dietary restriction compromises resistance to gut ischemia-reperfusion, despite reduction in circulating leukocyte activation.
abstract: BACKGROUND
  Gut ischemia-reperfusion (gut I/R) accompanying severe surgical insults leads to neutrophil-mediated injury and is regarded as a triggering event in early multiple-organ failure. Our previous study demonstrated dietary restriction to down-regulate leukocyte activation. Therefore, we hypothesized dietary restriction might be beneficial in terms of surviving I/R. We also evaluated leukocyte activation and the level of organ glutathione, an antioxidative substance.
  
  
  METHODS
  Institute of Cancer Research mice received chow, 170 (ad libitum), 119 (MR: mild restriction) or 68 (SR: severe restriction) g/kg per day for 7 days. Exp. 1: The mice (n = 59) underwent 15 or 45 minutes of gut ischemia and survival was observed. Exp. 2: The mice (n = 73) were killed before or 60 or 120 minutes after 15-minute ischemia. Reactive oxygen intermediate (ROI) production by circulating myeloid cells and CD11b expression was determined. Some mice were assessed for nuclear factor kappa B (NFkappaB) activation. Glutathione levels were measured in some of the small intestine and liver samples from each group.
  
  
  RESULTS
  Dietary restriction decreased survival. Circulating myeloid cell priming and activation, in terms of ROI production and CD11b expression, were enhanced in the ad libitum group but not in the restricted groups. NFkappaB was activated only in the ad libitum group. Gut and hepatic glutathione levels were lower in the SR than in the ad libitum group. Dietary restriction caused histologic damages in gut, liver, and lung 120 minutes after reperfusion.
  
  
  CONCLUSIONS
  Dietary restriction blunts leukocyte priming and activation after gut ischemic insult but worsens the outcome by, at least in part, decreasing antioxidative activities. Clinically, nutrition replenishment may be required to improve the outcome of gut hypoperfusion.
authors.affiliation: Department of Surgery I, Division of Basic Traumatology, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Ueno
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fukatsu
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Maeshima
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Moriya
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinto
authors.forename: Etsuko
authors.initials: E
authors.lastname: Hara
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nagayoshi
authors.forename: Hoshio
authors.initials: H
authors.lastname: Hiraide
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Mochizuki
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism*; D007108:Immune Tolerance; D007421:Intestine, Small / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009102:Multiple Organ Failure / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism; D013217:Starvation / Q000276:immunology*; D016019:Survival Analysis
chemical_list: D017382:Reactive Oxygen Species; D005978:Glutathione