The effects of phenylbutazone on the intestinal mucosa of the horse: a morphological, ultrastructural and biochemical study.
Phenylbutazone, a non-steroidal anti-inflammatory drug known to produce intestinal erosions, was administered intravenously (13.46 mg/kg bodyweight) to 12 horses which were killed after 24, 48, 72 and 96 h. Eight untreated horses served as controls. Annular erosions in the duodenum and mucosal necrosis in the colon were seen after 48 h which progressed in severity. The erosions were characterised by sloughing of the surface epithelium, subepithelial cleft and bleb formation, necrosis of the lamina propria, degeneration of the walls of subsurface capillaries and microthrombosis. Large numbers of neutrophils with abundant fibrin and cellular debris were present at the erosion sites. Ultrastructurally, there was swelling of the endothelium of capillaries and small vessels, and of pericyte and smooth muscle cytoplasm in arterioles. In capillaries and post capillary venules, the endothelium ranged from swollen to lysed and necrotic. Extensive extravasation of erythrocytes and oedema were seen. These lesions were not seen in the control horses. Phenylbutazone produces a microvascular injury associated with the formation of duodenal and colonic erosions in horses. The duodenal and colonic mucosa were assayed at 48 and 96 h for prostacyclin and PGE2. There was no statistically significant difference between prostaglandin levels in the mucosa of control and treated horses. It was concluded that there was no correlation between mucosal prostaglandin levels and intestinal erosions after 48 h.
Meschter
C L
CL
Department of Pathology and Equine Drug Testing and Toxicology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853.
Gilbert
M
M
Krook
L
L
Maylin
G
G
Corradino
R
R
D000818:Animals; D003106:Colon / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D015232:Dinoprostone / Q000032:analysis; D004386:Duodenum / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D011464:Epoprostenol / Q000032:analysis; D005260:Female; D006736:Horses / Q000033:anatomy & histology*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D010653:Phenylbutazone / Q000633:toxicity*
D011464:Epoprostenol; D010653:Phenylbutazone; D015232:Dinoprostone