Effects of okadaic acid on rat colon

• Published in: Digestive diseases and sciences Vol. 43; no. 11; pp. 2526 - 2535
• Main Authors: HOSOKAWA, M, TSUKADA, H, SAITOU, T, KODAMA, M, ONOMURA, M, NAKAMURA, H, FUKUDA, K, SEINO, Y
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.11.1998; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Colon - anatomy & histology; Colon - drug effects; Colon - enzymology; Colon - physiology; Colonoscopy - methods; Diarrhea - chemically induced; Drug toxicity and drugs side effects treatment; Electric Conductivity; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Intestinal Mucosa - anatomy & histology; Intestinal Mucosa - drug effects; Intestinal Mucosa - enzymology; Intestinal Mucosa - physiology; L-Lactate Dehydrogenase - drug effects; Male; Medical sciences; Microscopy - methods; Okadaic Acid - administration & dosage; Okadaic Acid - pharmacology; Pharmacology. Drug treatments; Rats; Rats, Wistar; Thrombosis - chemically induced; Time Factors; Toxicity: digestive system; Electron microscope; Rat; Rodentia; Cardiovascular disease; Laparoscopy; Experimental study; Route of administration; Thrombosis; Colonic disease; Vascular disease; In vivo; Microcirculation; Vertebrata; Mammalia; Histopathology; Animal; Risk factor; Digestive diseases; Okadaic acid; Colon
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1023/A:1026658921369

Effects of okadaic acid (OA) on mucosal damage were examined in rat colon. OA was sprinkled on rat colon mucosa under observation with an electronic-endoscopic system, and OA was also applied to the in vivo microscopic field. The OA-induced changes in transepithelial conductance (Gt) were measured by the Ussing voltage clamp technique. By endoscopic observation, the luminal sprinkling of OA (60 nmol/kg) evoked transient microthrombi in the submucosal venule, which was followed by mucosal edema. Histological study after endoscopic observation showed submucosal fluid retention, suggesting an increase of vascular permeability. The microthrombi were also detected by in vivo microscopy. By electrophysiological study after endoscopic observation with and without OA addition, the basal Gt values were 54+/-6.2 and 36.2+/-4.2 mS/cm2, respectively (P < 0.01). Furthermore in control rats, the serosal addition of OA evoked an increase in Gt in a concentration-dependent manner without increasing lactate dehydrogenase release. 2,4,6-Triaminopyrimidinium inhibited OA-induced Gt change by 60%. These results indicate that OA evokes an increase in paracellular permeability of epithelium. We conclude that the developed microthrombi are the first key event of OA-induced mucosal damage, followed by an increase in permeability in the submucosal venule and in the paracellular pathway of the epithelium.