Tolvaptan regulates aquaporin-2 and fecal water in cirrhotic rats with ascites
| Autor: | Wen-You Zhang, Haihua Lin, Renpin Chen, Chao Chen, Zhiming Huang, Xie-Lin Huang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Diarrhea
Male 0301 basic medicine Vasopressin medicine.medical_specialty Time Factors Cirrhosis Colon Vasopressins H&E stain Tolvaptan CCL4 030204 cardiovascular system & hematology Liver Cirrhosis Experimental Rats Sprague-Dawley Feces 03 medical and health sciences fluids and secretions 0302 clinical medicine Internal medicine Ascites medicine Animals Carbon Tetrachloride Aquaporin 2 Dose-Response Relationship Drug business.industry Reabsorption Sodium Gastroenterology Water General Medicine Basic Study Benzazepines medicine.disease 030104 developmental biology Endocrinology medicine.symptom business medicine.drug |
| Zdroj: | World Journal of Gastroenterology. 22:3363-3371 |
| ISSN: | 1007-9327 |
| DOI: | 10.3748/wjg.v22.i12.3363 |
| Popis: | AIM: To investigate the role of tolvaptan in regulating aquaporin (AQP)-2 expression and fecal water content in cirrhotic rats with ascites. METHODS: Cirrhosis with ascites was induced in rats by repetitive dorsal injection of CCl4 for 14 wk. In total, 84 cirrhotic rats with ascites divided into three groups (vehicle, 3 mg/kg and 5 mg/kg tolvaptan), and then further divided into five subgroups (days 1, 2, 3, 4, and 5). Blood samples were obtained to measure vasopressin and sodium concentrations. Rats were killed and colonic mucosa was scraped for analysis of protein expression and AQP-2 transcriptional level. The whole layer was fixed for hematoxylin&eosin (HE) staining and feces were collected for determination of fecal water content. CONCLUSION: Compared with vehicle, vasopressin decreased significantly in the tolvaptan groups from day 2 to a similar level in each treatment group. AQP-2 showed significant upregulation in cirrhotic rats with ascites compared with an untreated control group (100% ± 22.9% vs 22.2% ± 10.23%, P < 0.01). After administration of tolvaptan, AQP-2 expression began to decrease significantly from day 2 in each treatment group, but no significant difference was finally found between the treatment groups. Fecal water content in the distal colon was increased by 5 mg/kg tolvaptan on day 1 (66.8% ± 9.3% vs 41.4% ± 6.3%, in the vehicle group, P < 0.05). Fecal water content returned to baseline at day 4 at the latest in both treatment groups, and did not correspond to the change in AQP-2 expression. HE staining of the colonic mucosa showed no mucosal damage related to tolvaptan. CONCLUSION: Upregulation of AQP-2 in the distal colon is found in cirrhotic rats with ascites. Tolvaptan inhibits its expression and may decrease water reabsorption and induce diarrhea. |
| Databáze: | OpenAIRE |
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