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Hepato-Renal Protective Potential of Dimethyl Fumarate in Alloxan-Induced Diabetic Mice Model by Modulating of Sirt1,
Parisa Saberi-Hasanabadi1,2, Fatemeh Shaki2, Mohammad Karami2
1Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
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.
Insights
Dimethyl fumarate shows promise in treating diabetes by improving blood sugar, protecting organs, and reducing inflammation in mice. Further clinical studies are recommended to explore its therapeutic potential in humans.
Area of Science:
- Pharmacology
- Toxicology
- Biochemistry
Background:
- Diabetes mellitus remains a significant global health challenge with inadequate treatment options.
- Effective medication-assisted treatments are crucial for managing diabetes and preventing its complications.
- Dimethyl fumarate is being investigated for its potential therapeutic effects in various conditions.
Purpose of the Study:
- To evaluate the anti-diabetic and hepato-renal protective effects of dimethyl fumarate.
- To investigate the impact of dimethyl fumarate on oxidative stress and inflammatory pathways in a type 1 diabetes mouse model.
- To explore the modulation of Sirt1/Nrf2 and inflammatory gene expression by dimethyl fumarate.
Main Methods:
- Type 1 diabetes was induced in mice using alloxan.
- Mice were treated with varying doses of dimethyl fumarate (20, 40, 80 mg/kg) for 21 days.
- Blood biochemical parameters, oxidative stress markers, inflammatory gene expression (TNF-α, IL-6, NF-κB, Sirt1, Nrf2), and histopathological changes in kidneys and livers were assessed.
Main Results:
- Dimethyl fumarate demonstrated significant anti-diabetic effects, improving blood glucose levels and oxidative stress markers.
- Histopathological examination revealed protective effects on kidney and liver tissues in dimethyl fumarate-treated diabetic mice.
- Dimethyl fumarate treatment led to decreased expression of pro-inflammatory cytokines (TNF-α, IL-6, NF-κB) and increased expression of Sirt1 and Nrf2.
Conclusions:
- Dimethyl fumarate exhibits hepato-renal protective effects in an alloxan-induced diabetic mouse model.
- These protective effects are attributed to the attenuation of reactive oxygen species and inflammatory pathways via modulation of Sirt1/Nrf2 and inflammatory gene expression.
- The findings support further clinical investigation of dimethyl fumarate as a potential diabetes treatment.
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