Abstract
Aims: In numerous cases, patients with inflammatory bowel diseases (IBDs) are refractory to standard treatment. Sirolimus (SIR) and tacrolimus (TAC) are immunosuppressant drugs with encouraging outcomes. However, they have side effects causing limitations in their use. Metformin (MET), which is an antidiabetic drug, has promising anti-inflammatory effects. Thus, this study aimed to validate the effect of the concomitant administration of MET and SIR or TAC in the management of experimentally induced colitis.
Study Design: Dextran sulphate (DSS) induced colitis model was used.
Methodology: Colitis was induced by administering 5% DSS in water twice daily via oral gavage for 9 days. MET 200 mg/kg alone or in combination with SIR 1 mg/kg or TAC 1 mg/kg was started on day 7 and was continuously administered for 12 days. Then, samples of distal colon tissues were collected for histopathological and immunohistochemistry staining. Then, the proinflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-6, and IL-17A levels in tissue homogenates were measured.
Results: MET, SIR or TAC significantly attenuated the effect of DSS and the levels of all proinflammatory cytokines. Moreover, adding MET reinforces the effect of SIR and TAC.
Conclusion: MET had a strong anti-inflammatory effect against DSS-induced colitis. Hence, it could be a promising adjuvant therapy in the management of IBDs. The effect was mediated, in part, by inhibiting NF-kB activation. However, the results of this study must be further validated and translated to clinical implications.