Prevention of dexamethasone-induced lymphocytic apoptosis in the intestine and in Peyer patches by enteral nutrition.
BACKGROUND
Apoptosis is a programmed cell death, genetically controlled, that can be activated by physiological and pathophysiological events and by the administration of several drugs, including the exogenous administration of corticosteroids. The aim of this study was to develop a rat model of intestinal lymphocytic apoptosis induced by dexamethasone to determine if apoptosis could be prevented by enteral or parenteral nutrition.


METHODS
Male Sprague-Dawley rats were used. On day 0, the right internal jugular vein was catheterized for parenteral nutrition, and a silicone tube was inserted into the duodenum for enteral feeding. Animals (n = 6/group) were randomly assigned to one of the following 3 feeding regimens: an immune-enhancing enteral diet; its placebo (the same formula without immunonutrients); and isocaloric isonitrogenous parenteral nutrition. On the seventh day, 200 microg of dexamethasone or vehicle were administered by i.v. bolus, and the diets were continued for 1 more day. Intestinal Peyer patches and thymic lymphocytic apoptosis were determined both by flow-cytometry and immunohistochemistry.


RESULTS
A single dexamethasone dose (200 microg/rat) administered to surgically treated rats fasted for 18 hours, 24 hours later, caused massive intestinal and Peyer patches lymphocytic apoptosis (96 +/- 2% and 85 +/- 5%, respectively; p < .0001 versus vehicle in both kinds of tissue). Lymphocytic apoptosis was reduced to almost indetectable levels in intestinal and lamina propia lymphocytes (from 96 +/- 2% to <0.6%; p < .0001). Peyer patches lymphocytic apoptosis was reduced as well (from 85 +/- 5% to 15 +/- 7.1%; p < .001) in animals prefed the 2 enteral nutrition formulas. Those prefed parenteral nutrition only showed a partial decrease of lymphocytic apoptosis in the intestine (from 96 +/- 2% to 53 +/- 23%; p < .001). Nutrition had no effect on the dexamethasone-induced thymus involution.


CONCLUSIONS
Enteral nutrition prevents intestinal intraepithelial and lamina propia lymphocytic apoptosis due to dexamethasone. These findings support the use of early enteral nutrition in critically ill patients treated with corticosteroids.
Ruiz-Santana
S
S
Intensive Care and Research Unit, Hospital Universitario General de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain. srviz@correo.hpino.rcanaria.es
López
A
A
Torres
S
S
Rey
A
A
Losada
A
A
Latasa
L
L
Manzano
J L
JL
Díaz-Chico
B N
BN
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003907:Dexamethasone / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004750:Enteral Nutrition; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000633:toxicity*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D010288:Parenteral Nutrition; D010581:Peyer's Patches / Q000276:immunology* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D005938:Glucocorticoids; D003907:Dexamethasone