Gastrointestinal Side Effects of Triple Immunosuppressive Therapy Evaluated by AC Biosusceptometry and Electrogastrography in Rats.

BACKGROUND: Triple immunosuppressive therapy is associated with several gastrointestinal disorders. The aim of this study was to investigate the effects induced by the triple immunosuppressive therapy on the gastrointestinal tract of rats. METHODS: Male Wistar rats were randomly assigned into three experimental groups: Control: filtered water; TAC + MPS + PRED: treated with Tacrolimus plus Mycophenolate Sodium plus Prednisone; and CSA + AZA + PRED: treated with Cyclosporine plus Azathioprine plus Prednisone. The treatment was done for 14 days by gavage. Gastric emptying and contractility were evaluated by the Alternating Current Biosusceptometry (ACB) and Electrogastrography (EGG). Histological, biochemical and hematological analyses were also performed. RESULTS: Gastric emptying time was slower in the CSA + AZA + PRED group in comparison with control (p<0.01) and TAC + MPS + PRED groups (p<0.001). Animals treated with TAC + MPS + PRED showed accelerated gastric emptying (p<0.05) compared to control. The amplitude of gastric contractions in both immunosuppressed groups was higher than observed in the control. The frequency of gastric contractions for the CSA + AZA + PRED group was also increased (p<0.01). Results obtained by EGG were similar to those recorded with the ACB. The thickness of the circular layer from stomach muscle decreased in both immunosuppressed groups, while the longitudinal layer was reduced only in the CSA + AZA + PRED group. CONCLUSION: Triple immunosuppressive therapy alters gastric motility, compromises the muscular layers and the association between CSA, AZA, and PRED provokes the major alterations in the structure and gastric function. Specific gastrointestinal side effects resulting from different immunosuppressive therapies still need to be elucidated in order to provide more effective and personalized therapy for patients.

Gastrointestinal effects of ivermectin treatment in rats infected with Strongyloides venezuelensis.

We aimed to evaluate the effects of ivermectin treatment on gastrointestinal morphology and function after Strongyloides venezuelensis infection. Male rats composed Control (C), Parasitized (Sv), Ivermectin (IVM) and Parasitized and treated with Ivermectin (Sv/IVM) groups. IVM and Sv/IVM groups were subdivided according to IVM: single dose of 200 µg/kg (IVM1 and Sv/IVM1) or three repeated doses of 200 µg/kg at 24 h intervals (IVM3 and Sv/IVM3). First dose of IVM was administered after peak of infection. Eggs per gram (EPG), mean gastric emptying time (MGET), mean cecum arrival time (MCAT) and mean small intestinal transit time (MSITT) were evaluated. Measurements were performed before drug and at peak of infection, first day post peak of infection and 30 days post infection. Same time intervals were simulated for uninfected animals. Number of recovered worms and intestinal morphometry were also rated. Data were analyzed by ANOVA and correlated by Dunnett and Pearson (p < 0.05). Sv/IVM1 and Sv/IVM3 showed reduction of EPG and worms, although only group SV/IVM3 eradicate them. Hastened gastric emptying and slowed intestinal transit provoked by S. venezuelensis infection can be reverted by a single administration of IVM after peak of infection, even without total parasite elimination. Although three consecutive doses of IVM were more efficient to eradicate the parasite, drug administration impaired gastrointestinal function and morphology. IVM alone affected gastrointestinal parameters in uninfected animals for prolonged periods, especially in high doses. In control, there were strong negative correlations between MSITT and muscle layers. Strongyloides venezuelensis infection abolishes such correlations. Longitudinal muscle was thinner in IVM3 and Sv/IVM3 groups and circular thicker in Sv group. Revisiting the action of traditional drugs broadens knowledge in the parasite-host interface and may result in the development of more accurate therapeutic strategies.