Dietary restriction compromises resistance to gut ischemia-reperfusion, despite reduction in circulating leukocyte activation.
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.
Ueno
Chikara
C
Department of Surgery I, Division of Basic Traumatology, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Fukatsu
Kazuhiko
K
Maeshima
Yoshinori
Y
Moriya
Tomoyuki
T
Shinto
Eiji
E
Hara
Etsuko
E
Nagayoshi
Hidetoshi
H
Hiraide
Hoshio
H
Mochizuki
Hidetaka
H
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
D017382:Reactive Oxygen Species; D005978:Glutathione