Introduction: Diabetes mellitus is a growing epidemic and is the most common cause of chronic kidney disease and liver failure. Therefore, there is an urgent need to develop more effective medication-assisted treatments.
Methods: In this study, forty female mice were divided into eight groups with five animals in each. Type 1 diabetes mice models was established using multiple low-dose alloxan, and the diabetic mice were treated with three doses of dimethyl fumarate (DMF) i.e low, medium, and high viz. 20, 40 and 80 mg/kg, respectively for a period of 21 days. Then, specific test were done to evaluate blood biochemical parameters, oxidative stress markers, inflammatory cytokine, and histopathological changes in mice kidney and liver.
Results: Diabetic liver and kidney tissue showed marked dilation of bile ducts, tubules, infiltration, and inflammation. In addition, nuclear factor erythroid-2 related factor 2 (Nrf2) and its downstream effectors (Sirt1) were suppressed in these two diabetic tissues (p< 0.001). On the contrary, diabetic mice treated with DMF showed improvement in oxidative stress indices, inflammation, and this with increased Nrf2 and Sirt1 activation (p< 0.001).
Conclusion: Collectively, it can be concluded that the role of DMF as a blood sugar reducer and improvement of diabetes complications is very significant, likely via reducing activation of pro-inflammatory cytokines function. Although, some contradictory effects of inflammatory factors were observed in kidney and liver tissues, but overall, the therapeutic combination of DMF and metformin (MET) has a good hepato-renal protective ability in alloxan-induced diabetic mice model.