The synergistic renoprotective effects of valproate sodium and metformin in a diabetic nephropathy mouse model: attenuation of pro-inflammatory markers and enhancement of Sirt1 and Bcl-2 expression

Diabetic nephropathy is a serious and common complication among patients with both type 1 and type 2 diabetes, and it significantly reduces the patient's quality of life. This study aimed to assess the reno preventive effects of valproate sodium (VPS) and metformin (MET) on alloxan-induced diabetic nephropathy and to elucidate their mechanisms of action, 'type 1 diabetic mice' (25-30 g) were established using a single dose 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) for a period of 28 days. Specific tests were performed to evaluate inflammatory gene expression (TNF-α, IL-6, and NF-κB) and histopathological changes and apoptotic factors (Bax/Bcl2, Caspase3). Our results have shown, VPS and MET led to significant decreases in blood glucose levels, thereby reflecting the improvement of impaired kidney function and decreasing elevated renal mRNA levels of inflammatory genes (TNF-α, IL-6, and NF-κB) in diabetic mice. A significant increase in the expression of be 'Sirt1 and Bcl-2' and decrease in (TNF-α, IL-6, and NF-κB) was observed in the kidneys of diabetic mice receiving MET/VPS Moreover, MET/VPS successfully prevented diabetes induced 'histopathological deleterious changes' in the kidneys of mice so it can concluded that MET and VPS alone or in combination can prevent alloxan-induced diabetic nephropathy through attenuating inflammatory markers and probably with suppression of apoptosis.