Hepato‐Renal Protective Potential of Dimethyl Fumarate in Alloxan‐Induced Diabetic Mice Model by Modulating of Sirt1, Nrf2 and Inflammatory Genes Expressions

AIM: Despite advances in diabetes treatments, the effects of this disease have not yet been adequately reversed or prevented in patients. Therefore, development of more effective medication-assisted treatments in this field is needed. METHOD: Type 1 diabetes mice models were established using multiple low-dose alloxan, then were treated with three doses of dimethyl fumarate, that is, low, medium and high viz. 20, 40 and 80 mg/kg, respectively for 21 days. Then, specific tests were done to evaluate blood biochemical parameters, oxidative stress markers, inflammatory genes expression and histopathological changes in the mice kidneys and livers. RESULTS: Improved anti-diabetic, hepato-renal protective and oxidative stress indexes of dimethyl fumarate in diabetic mice were shown. The histological features improved in comparison with diabetic mice. The real-time PCR results indicated a decrease in the alloxan-induced elevations in mRNA levels of pro-inflammatory cytokines such as TNF-α, IL-6 and NF-κB levels in both kidney and liver tissues of diabetic mice. Meanwhile, dimethyl fumarate showed an increase in Sirt1 and Nrf2 expression in comparison to the diabetic group. CONCLUSIONS: In total, it can be concluded that dimethyl fumarate treatment provides hepato-renal protective effects on alloxan-induced diabetic mice model by attenuating reactive oxygen species inflammatory pathways through modulating Sirt1/Nrf2 and inflammatory genes expressions. This study can be an introduction to further studies on the basis of diabetes treatment, especially clinical studies to demonstrate the effect of dimethyl fumarate in diabetes.