Evaluation of protective effect of Aegle marmelos fruit (Bael) on Mycophenolate mofetil and Mycophenolate Sodium induced gastrointestinal toxicity in mice.

Mycophenolate mofetil (MMF) and Mycophenolate sodium (MPS) are the common allopathic drugs used in the prevention of graft rejection during transplantation and various autoimmune disorders. Clinically, MMF and MPS are known to cause various adverse effects, with diarrhea, weight loss and gastric ulcer as the most common events. This study aimed to minimize MMF / MPS associated diarrhea, weight loss and gastric ulcer upon co-administration of aq. extract of ripe fruit of Aegle marmelos (AM).Traditionally, the plant has been used for the improvement of GI function. Methods: Ten groups of mice (n=6) were selected and dosed as: control (CMC 1%), MMF (210mg/kg), and MMF (210 mg/kg) followed by AM (100mg/kg), MMF (210 mg/kg) followed by AM (200mg/kg) and MMF (210 mg/kg) followed by Loperamide (3mg/kg). MPS (100mg/kg), and MPS (100 mg/kg) followed by AM (100mg/kg) and MPS (100 mg/kg) followed by AM (200mg/kg) and MPS (100 mg/kg) followed by Loperamide (3mg/kg). And standard: Loperamide (3mg/kg). Weight loss, diarrhea grade were monitored for six days. In second part of study, four group of mice (n=6) were selected and dosed as: control castor oil (1ml) followed by vehicle, Loperamide (3mg/kg) followed by castor oil (1ml), AM (100 & 200mg/kg) followed by castor oil (1ml) and diarrhea grade were monitored. In third part of study ten groups of mice (n=6) were selected and dosed as: control (CMC 1%), MMF (210mg/kg), and MMF (210 mg/kg) followed by AM (100mg/kg), MMF (210 mg/kg) followed by AM (200mg/kg) and MMF (210 mg/kg) followed by Ranitidine (10mg/kg). MPS (100mg/kg), and MPS (100 mg/kg) followed by AM (100mg/kg) and MPS (100 mg/kg) followed by AM (200mg/kg) and MPS (100 mg/kg) followed by Ranitidine (10mg/kg). And standard: Ranitidine (10mg/kg), after 4 hours of last dose of the treatment, the animals were sacrificed, and ulcer index evaluated. In fourth part of the study, eleven groups of mice (n=6) were selected for evaluation of antiulcer properties of AM using pylorus ligation technique. The animals were dosed as: Control (distilled water 2mL/kg), AM treated (200mg/kg), MMF (210mg/kg), MPS (100mg/kg), standard group Ranitidine (10mg/kg), and MMF (210mg/kg) followed by AM (100 and 200 mg/kg) and MMF (210mg/kg) followed by Ranitidine (10mg/kg), MPS (100mg/kg) followed by AM (100 & 200mg/kg) and MPS (100 mg/kg) followed by Ranitidine (10mg/kg). After 4 hours of last dose of the treatment, the animals were sacrificed, and ulcer index evaluated. Result: MMF and MPS were found to induce diarrhea (p<0.001) and weight loss by 6th day. Castor oil also induced diarrhea. MMF and MPS treated groups induced gastric ulcer (p<0.001). Pylorus ligation induced gastric ulcer in presence or absence of MMF and MPS (p<0.001). The groups treated with AM showed significant recovery, as found to have low or no diarrhea (as indicated by diarrhea grade), reduced weight loss, and protection against gastric ulcer induced by MMF and MPS (p<0.001), in comparison to the respective control groups. In pylorus ligation study, the animals in the groups treated with AM, were found to have lower ulcer index (p<0.001) in comparison to the MMF treated group, MPS treated group or control group animals. Conclusion: Aegle marmelos was found to provide significant protection against the MMF and MPS induced GI toxicity in mice as indicated by lower levels of diarrhea grade, weight loss and ulcer index.