Development of cysteamine-induced ultrastructural surface changes on duodenal mucosa.
Duodenal ulcers were induced acutely in female rats by a single oral administration of cysteamine, 70 mg/100 gm, in order to study morphologic progression of lesion development from the perspective of cellular surface changes by scanning electron microscopy. Thick sections of resin-embedded specimens were also studied by light microscopy, and animals were sacrificed at intervals of 30 minutes, 1, 2, 4, 8, 12, 20, and 24 hours post-treatment. Earliest evidence of cytologic lesions was apparent at 2 hours and data confirmed earlier reports that alterations began at villous tips. Both cellular sloughing and in situ cellular injury were evident, the latter phenomenon constituting the principal mode of cysteamine-induced erosion. In situ change began, from surface perspective, as a minute cavitation on the apical aspect of an isolated, single epithelial cell which was surrounded by normal cells. These early lesions progressed to in situ necrosis either of isolated cells or of small clusters of adjacent cells. This phenomenon occurred concurrently on multiple villi, all within the localized site at which cysteamine-induced duodenal ulcers are known to develop. An additional early morphologic change was the occasional appearance of a background of pleomorphic cellular apices of variable size on the villous ridges. By 8 to 12 hours, cellular damage advanced to erosions with some cells in the preulcer area still showing initial stages of in situ cellular injury. Precipitated mucus on the surface was increased in the preulcer area, and by 20 to 24 hours typical duodenal ulcers were evident. These scanning electron microscopic data confirm the significance of surface damage at villous tips very early in the cysteamine-induced ulcerogenesis. The present higher resolution findings demonstrated that earliest cellular damage, principally in situ cell injury, occurred simultaneously at multiple sites in the preulcer zone rather than at a single cluster of cellular damage which enlarges peripherally.
D000818:Animals; D003543:Cysteamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D004386:Duodenum / Q000187:drug effects / Q000648:ultrastructure*; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects / Q000648:ultrastructure*; D008855:Microscopy, Electron, Scanning; D008871:Microvilli / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains
D003543:Cysteamine