The effects of thermal injury on transcellular permeability and intestinal P-glycoprotein in rats.
This study was designed to assess intestinal drug transport via transcellular absorption and intestinal P-glycoprotein content following thermal injury in rats using propranolol as a marker substrate. Male, Sprague Dawley rats (n=30) underwent either a 30% total body surface area full thickness burn or sham treatment. Twenty-four hours later, animals were anesthetized, underwent laparotomy and the proximal jejunum was cannulated. The jejunal segment was perfused with buffer containing [3H] propranolol. Following euthanasia, jejunal tissue was harvested for Western immunoblotting of P-glycoprotein and villin, and immunohistochemical analysis of P-glycoprotein. Dramatic structural changes in jejunal integrity were observed following thermal injury; however, no significant differences in the absorption characteristics of propranolol following thermal injury were observed. Mean effective permeability of propranolol was 5.67+/-1.79 and 5.85+/-1.67cm/sx10(-5) for burn and sham groups, respectively (P>0.05). P-glycoprotein and villin content in the jejunum were significantly decreased in burn animals. The transcellular transport of propranolol is unaffected 24h following thermal injury in rats, despite alterations in intestinal P-glycoprotein content. The decrease in P-glycoprotein and villin content in thermally injured animals may reflect loss of mature enterocytes at the villus tips.
Neudeck
Brien L
BL
The University of Wisconsin School of Pharmacy, Madison, WI, USA.
Foster
David R
DR
Li
Lilian Y
LY
Gonzales
Jeffrey P
JP
Welage
Lynda S
LS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000818:Animals; D002056:Burns / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis; D007150:Immunohistochemistry / Q000379:methods; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis; D011433:Propranolol / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008840:Microfilament Proteins; C026615:villin; D011433:Propranolol