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

Abstract

What is the central question of this study? The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. What is main finding and its importance? In our experimental study, immunosuppressive drugs currently in use accelerated gastric emptying whilst increasing the frequency and amplitude of gastric contractions after treatment, except for Mycophenolate and azathioprine. Alternating current biosusceptometry is a useful tool to evaluate side-effects of drugs on the gastrointestinal tract, which will help in understanding the symptoms and improving clinical management of patients. The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. Male Wistar rats were randomly distributed into the following treatment groups: ciclosporin, tacrolimus, prednisone, sirolimus, mycophenolate mofetil, everolimus, azathioprine and control. Each animal was treated for 14 days by gavage with dosages ranging from 1 to 20 mg kg day considering the area-to-volume ratio and hepatic metabolism. Gastrointestinal transit and gastric contractility measurements were evaluated by alternating current biosusceptometry before and after treatment. Gastric emptying was faster in animals treated with tacrolimus, prednisone, sirolimus and everolimus compared with control animals (126.7 ± 12.7 min). There was a significant increase in the frequency of contractions after ciclosporin, tacrolimus, azathioprine and sirolimus treatment compared with control animals (4.6 ± 0.3 cycles min ). Increases in the amplitude of contraction were observed after treatment with tacrolimus, sirolimus and everolimus compared with control rats (34.9 ± 6.0 dB). 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 non-invasive technique, alternating current biosusceptometry is a potentially useful tool for evaluation of side-effects of drugs in gastrointestinal tract, helping us to understand the symptoms to improve clinical management of patients.

Role of gastric peroral endoscopic myotomy (GPOEM) in chronic gastroparesis management after pancreas transplantation

“…33,34 One study measured GI contractility in multiple immunosuppressants but did not note any change in GI transit with mycophenolate mofetil. 35 In our practice, we have not appreciated any connection with DGE and mycophenolate mofetil, so it remains in our initial approach to immunosuppression for PTA. Although, more recently, we utilized oral mycophenolic acid 360 mg twice a day in place of mycophenolate mofetil as a component of maintenance immunosuppression.…”

Post-Transplant Diarrhea is Associated with Increased Rejection in Lung Transplant Recipients: A Retrospective Review

“…This suggests that tacrolimus itself is toxic to the GI epithelium, thereby leading to diarrhea. Furthermore, tacrolimus may have an effect on intestinal motilin receptors to some degree given its' macrolide structure [13].…”

Baru (Dipteryx alataVogel) almond and dairy desserts with baru regulates gastrointestinal transit in rats

“…The ACB is a magnetic technique validated to register several parameters of GI motor function in rats (Américo et al, 2010;Dall'Agnol et al, 2017;Mendonça et al, 2019). Magnetic signals generated by magnetic material ingestion are detected by ACB sensor (Br4Science, Brazil) and the signal intensity depends on the amount of magnetic material and its distance from the sensor (Américo et al, 2010).…”

“…For following up gastrointestinal transit during baru intake in the same animal, alternative methodologies are necessary. Alternate current biosusceptometry (ACB) is an inexpensive, radiation‐free, and noninvasive method previously employed as a reliable technique to record gastrointestinal transit and contractility in rodents (Dall'Agnol et al, ; Mendonça, Gama, Hauschildt, Corá, & Américo, ).…”

“…Alternate current biosusceptometry (ACB) is an inexpensive, radiation-free, and noninvasive method previously employed as a reliable technique to record gastrointestinal transit and contractility in rodents (Dall'Agnol et al, 2017;Mendonça, Gama, Hauschildt, Corá, & Américo, 2019).…”