The effects of thermal injury on transcellular permeability and intestinal P-glycoprotein in rats.

Abstract

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.