Mazandaran University of Medical Sciences, Sari, Iran , dr.parisasaberi@gmail.com
Abstract: (117 Views)
Background: This study aimed to assess the synergistic reno-preventive effects of valproate sodium (VPS) and metformin (MET) on alloxan-induced diabetic nephropathy and to elucidate their mechanisms of action through investigation of the effects on renal modulation of the pro-inflammatory expression and enhancing the expression of Sirt1 and Bcl-2.
Methods: Type 1 diabetes mice (25-30 g) models was established using a single dose i.p of alloxan (120 mgkg-1), and the diabetic mice were treated with three doses of VPS (10, 20, and 40 mg/kg) and MET (200 mg/kg), respectively for a period of 28 days. Then, specific test were done to evaluate inflammatory genes expression and histopathological changes in the mice kidneys.
Results: The obtained data revealed that the treatment of diabetic mice with VPS and MET led to significant decreases in the blood glucose levels; thereby reflecting the improvement of the impaired kidney function. The treatment with MET and VPS in combination was the most potent in decreasing the elevated renal mRNA levels of inflammatory genes expressions in diabetic mice. Meanwhile, significant increase in the expression of Sirt1and Bcl2 was observed in the kidney of diabetic mice receiving MET/VPS as compared with the diabetic group. Moreover, the treatment of diabetic mice with MET/VPS successfully prevented the diabetes-induced histopathological deleterious changes of kidney.
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.
Methods: Type 1 diabetes mice (25-30 g) models was established using a single dose i.p of alloxan (120 mgkg-1), and the diabetic mice were treated with three doses of VPS (10, 20, and 40 mg/kg) and MET (200 mg/kg), respectively for a period of 28 days. Then, specific test were done to evaluate inflammatory genes expression and histopathological changes in the mice kidneys.
Results: The obtained data revealed that the treatment of diabetic mice with VPS and MET led to significant decreases in the blood glucose levels; thereby reflecting the improvement of the impaired kidney function. The treatment with MET and VPS in combination was the most potent in decreasing the elevated renal mRNA levels of inflammatory genes expressions in diabetic mice. Meanwhile, significant increase in the expression of Sirt1and Bcl2 was observed in the kidney of diabetic mice receiving MET/VPS as compared with the diabetic group. Moreover, the treatment of diabetic mice with MET/VPS successfully prevented the diabetes-induced histopathological deleterious changes of kidney.
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.
Keywords: Diabetes, valproate sodium, metformin, alloxan, diabetic nephropathy, reno-protective supports
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