We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Histopathology of Vascular Injury in Sprague-Dawley Rats Treated with Phosphodiesterase IV Inhibitor SCH 351591 or SCH 534385.
- Authors
JUN ZHANG; SNYDER, RONALD D.; HERMAN, EUGENE H.; KNAPTON, ALAN; HONCHEL, RONALD; MILLER, TERRY; ESPANDIARI, PARVANEH; GOODSAID, FEDERICO M.; ROSENBLUM, IRWIN Y.; HANIG, JOSEPH P.; SISTARE, FRANK D.; WEAVER, JAMES L.
- Abstract
Histopathological and immunohistochemical studies were conducted to characterize vascular injuries in rats treated with phosphodiesterase (PDE) IV inhibitors SCH 351591 or SCH 534385. Sprague-Dawley rats were administered PDE IV inhibitors by gavage at a range of doses and times. The two PDE IV inhibitors induced comparable levels of vascular injury, primarily in the mesentery and to a lesser extent in the pancreas, kidney, liver, small intestine, and stomach. Mesenteric vascular changes occurred as early as one hour, progressively developed over twenty-four to forty-eight hours, peaked at seventy-two hours, and gradually subsided from seven to nine days. The typical morphology of the vascular toxicity consisted of hemorrhage and necrosis of arterioles and arteries, microvascular injury, fibrin deposition, and perivascular inflammation of a variety of blood vessels. The incidence and severity of mesenteric vascular injury increased in a time- and dose-dependent manner in SCH 351591- or SCH 534385- treated rats. Mesenteric vascular injury was frequently associated with activation of mast cells (MC), endothelial cells (EC), and macrophages (MØ). Immunohistochemical studies showed increases in CD63 immunoreactivity of mesenteric MC and in nitrotyrosine immunoreactivity of mesenteric EC and MØ. The present study also provides a morphological and cellular basis for evaluating candidate biomarkers of drug-induced vascular injury.
- Subjects
BLOOD vessels; WOUNDS &; injuries; PHOSPHODIESTERASES; LABORATORY rats; MESENTERIC blood vessels; TOXICOLOGY; MAST cells; MACROPHAGES; BIOMARKERS
- Publication
Toxicologic Pathology, 2008, Vol 36, Issue 6, p827
- ISSN
0192-6233
- Publication type
Article
- DOI
10.1177/0192623308322308