Stress produced by gavage administration in the rat.
This research project examined the relationship between gavage administration of various vehicles and induction of the stress response, as defined by increased plasma corticosterone levels, in the rat. In addition, we assessed elicitation of clinical signs of distress and aspiration leading to airway/pulmonary changes. We studied various vehicles used in toxicology studies, including water, corn oil, and 1% methylcellulose/0.2% Tween 80. Male CD rats received a single gavage administration of vehicle, blood was collected 1 h after dosing for measurement of plasma corticosterone, and necropsies were performed 4 h after dosing. Gavage administration of corn oil at. 20 mL/kg, but not 1% methylcellulose/0.2% Tween 80 or water, induced a stress response in a volume-dependent fashion, resulting in elevated plasma corticosterone levels. This response was not due to aspiration, which occurred after administration of. 20 mL/kg of water or 1% methylcellulose/0.2% Tween 80 but not corn oil. Administration of corn oil at 40 mL/kg resulted in plasma corticosterone levels that were elevated for 4 h. The stress response produced by corn oil was not unique to this vehicle but also occurred after gavage administration of sesame, soybean, and peanut oils. Our data indicate that gavage dosing of lipid vehicles induces activation of the stress response, as indicated by increased adrenal output of corticosterone, in a volume-dependent fashion. In conclusion, gavage administration of various vehicles can result in aspiration, pulmonary injury, and/or elicitation of a stress response in a vehicle- and dose volume-dependent fashion. The results of our project suggest that dose volumes for gavage administration in the rat generally should not exceed 10 mL/kg.
Brown
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AP
Toxicology Research Laboratory, Department of Pharmacology, University of Illinois at Chicago, 1940 W. Taylor Street, Chicago, IL 60612-7353, USA.
Dinger
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N
Levine
B S
BS
D000284:Administration, Oral; D000818:Animals; D000830:Animals, Laboratory; D015415:Biomarkers / Q000097:blood; D003345:Corticosterone / Q000097:blood; D008297:Male; D051381:Rats / Q000523:psychology*; D013315:Stress, Psychological; D014116:Toxicology / Q000379:methods
D015415:Biomarkers; D003345:Corticosterone