Gastrointestinal disorders after immunosuppression: an experimental model to evaluate the influence of monotherapy on motility parameters

Abstract

Objectives. The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. Methods. Male Wistar rats were randomly distributed into groups: Cyclosporine, Tacrolimus, Prednisone, Sirolimus, Mycophenolate Mofetil, Everolimus and Azathioprine. Each animal was treated during 14 days by gavage with dosage ranging from 1 to 20 mg Kg⁻¹ day⁻¹ considering area per volume ratio and hepatic metabolism. Gastrointestinal transit and gastric contractility measurements were evaluated by Alternating Current Biosusceptometry (ACB) before and after treatment. Results. The gastric emptying was faster in animals treated with Tacrolimus, Prednisone, Sirolimus and Everolimus compared to control (126.7 ± 12.7 min). There was a significant increase in frequency of contractions after Cyclosporine, Tacrolimus, Azathioprine and Sirolimus treatment compared to control (4.6 ± 0.3 cpm). Increases in amplitude of contraction were observed after treatment with Tacrolimus, Sirolimus and Everolimus compared to control (34.9 ± 6.0 dB). Conclusion. The results showed that our animal model was suitable for demonstrating that most immunosuppressive drugs currently in use impaired at least one gastrointestinal motility parameter. As a noninvasive technique, ACB can be proposal as useful tool to evaluate side effects of drugs in GI tract helping to understand the symptoms to improve clinical management of patients.

This article is protected by copyright. All rights reserved

http://ift.tt/2qjUkag