Injury and recovery process of intestine caused by okadaic acid and related compounds.
The injuries and repair processes in the intestines of mice induced by dinophysistoxin 3 (DTX 3) were compared morphologically to those induced by okadaic acid (OA) and dinophysistoxin 1 (DTX 1). DTX 3 impaired intestinal villi by the oral route only, whereas OA and DTX 1 caused intestinal injury with both oral and intraperitoneal exposures. The character of the lesions caused by the 3 toxins and the recovery processes were highly similar. Within 5 min of dosing, the basal portion of the covering epithelium became homogeneous and peeled from the lamina propria, while the upper portion containing microvilli remained intact. There were two types of villous injury and recovery: 1) When the injuries were limited to the villi, new cells from the crypts moved upward and differentiated into columnar cells. 2) When injuries progressed into the glands of Lieberkuhn, clusters of crypt cells were exposed to the intestinal lumen, and in the most severe case they were completely separated. Villous fusion was often seen in the recovery process of the type 2 cases. Recovery from the injuries was almost completed within 2 days. When mice were pretreated with fusarenon-X, a mycotoxin which injuries undifferentiated crypt cells preferentially, the injury induced by OA to the intestinal crypts was exacerbated and the recovery was delayed.
Ito
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Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Japan.
Terao
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K
D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D004141:Dinoflagellida / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004988:Ethers, Cyclic / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007422:Intestines / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D007583:Jejunum / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008387:Marine Toxins / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009183:Mycotoxins / Q000633:toxicity; D019319:Okadaic Acid / Q000031:analogs & derivatives; D011714:Pyrans / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D014255:Trichothecenes / Q000494:pharmacology
D002273:Carcinogens; D004988:Ethers, Cyclic; D008387:Marine Toxins; D009183:Mycotoxins; D011714:Pyrans; D014255:Trichothecenes; C092883:dinophysistoxin 3; D019319:Okadaic Acid; C002469:fusarenon-X; C051904:dinophysistoxin 1