Parisa Saberi-Hasanabadi,
Volume 24, Issue 5 (12-2024)
Abstract
Background: Despite advances in diabetes-related treatments, the effects of the disease have not yet been adequately reversed or prevented in patients. Therefore, there is an urgent need to develop more effective medication-assisted treatments in this field.
Methods: In this study, 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 genes expression, and histopathological changes in the mice kidney and liver.
Results: The obtained results showed remarkably improved anti-diabetic, hepato-renal-protective, and oxidative stress indexes of DMF in alloxan-induced diabetic mice (P< 0.001). Treated mice with DMF demonstrated a noteworthy decrease in blood glucose levels when compared with diabetic group (P< 0.001). Diabetic liver and kidney tissues showed marked dilation of bile ducts, tubules, infiltration, and inflammation. On the contrary, the histological features of the treated mice with DMF improve as shown by normal size of glomerular capillaries along with decrease in less dilatation of ducts in comparison with diabetic mice. The real-time quantitative PCR results indicated that DMF injection decreased the alloxan-induced increase of significant elevations in mRNA levels of pro-inflammatory cytokines levels in both kidney and liver tissues. Meanwhile, mice treated with DMF showed an increase in Sirt1 and Nrf2 expression in comparison to diabetic group.
Conclusion: In conclusion, it can be concluded that DMF treatment provides hepato-renal protective effects on alloxan-induced diabetic mice model by attenuating ROS inflammatory pathways.
Parisa Saberi-Hasanabadi,
Volume 25, Issue 2 (7-2025)
Abstract
Background: Diabetes is the most common metabolic disease resulting from a relative deficiency of insulin secretion or action. This study aimed to evaluate the synergistic inhibitory effects of valproate sodium (VPS) and metformin (MET) on alloxan-induced diabetic nephropathy and to understand the mechanism of their effect on the expression pathway of inflammatory genes, Sirt-1 and Bcl-2.
Methods: Female mice (C57BL/6) were induced to have diabetes by intraperitoneal injection of a single dose of alloxan (120 mg/kg). Diabetic mice were treated with three doses of sodium valproate (10, 20, and 40 mg/kg) and a single dose of metformin (200 mg/kg) for a period of 28 days. The expression of inflammatory genes and histological changes in the kidneys of the mice were evaluated for a period of 28 days.
Results: The hyperglycemia induced by alloxan-induced diabetes was significantly reduced after a 28-day course of valproate sodium administration (P < 0.05). Combined treatment of sodium valproate with metformin significantly reduced the expression of inflammatory genes in the kidney tissue of diabetic mice. A significant increase in the expression of Sirt-1 and Bcl2 was observed in diabetic mice receiving valproate sodium and metformin compared to the diabetic group. Treatment of diabetic mice with valproate sodium and metformin prevented the adverse histopathological changes caused by renal nephropathy, which was accompanied by normal glomerular capillary size and reduced dilatation of the urinary tract compared to diabetic mice.
Conclusion: It can be concluded that MET and VPS in combination can prevent alloxan-induced diabetic nephropathy through attenuating inflammatory pathways and decreasing inflammatory genes expressions together probably with the suppression of oxidative stress, inflammation and apoptosis.
