Metformin as an Adjuvant Therapy Attenuates Dextran Sulphate Sodium-induced Acute Colitis in Rats: A Recent Study

Aims: Patients with inflammatory bowel diseases (IBDs) are often resistant to standard care. Immunosuppressive drugs such as sirolimus (SIR) and tacrolimus (TAC) have shown to be effective.

They do, however, have side effects that restrict 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 pro-inflammatory cytokine, tumour necrosis factor-alpha (TNF-?), interleukin (IL)-1?, 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 pro-inflammatory 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-?B activation. Given the magnitude of the efficacy of MET and its safety profile, this finding can be used as a basis for pilot clinical trials that aim to evaluate the effect of MET on IBD. However, the results of this study must be further validated and translated to clinical implications.