Carbohydrate restriction ameliorates nephropathy by reducing oxidative stress and upregulating HIF-1α levels in type-1 diabetic rats

Background: Carbohydrate restricted diet regimen is widely accepted as therapeutic approach for the treatment of kidney disease associated with type-2 diabetes, obesity and hypertensive disorders. The present study tested the influence of carbohydrate-energy restricted diet (CR) on type-1 diabetes induced renal dysfunction, hypoxia and structural alterations against diabetic rat group fed control diet (ad libitium). Methods: Male wistar rats weighing between 180 and 190 g were subjected to 30% carbohydrate energy restricted diet (CR) and diabetes was induced by administration of streptozotocin (45 mg/kg., i.p). Assessment of renal function was done after 4 weeks by determining the serum levels of creatinine, BUN, proteinuria. Oxidative stress was determined by estimating the reduced glutathione, malonaldehyde levels, catalase activity and extent of renal hypoxia by estimating the HIF-1 alpha levels in kidney tissue homogenates. Histological studies were conducted on kidney sections using hematoxylin and eosin, periodic acid-schiff staining. Results: Diabetic rats exhibited marked hyperglycemia and renal dysfunction developed in diabetic rats fed control diet (ad libitium) as shown by significantly elevated levels of serum creatinine, BUN and massive proteinuria after 4 weeks period. CR diet treatment in diabetic rats significantly lowered hyperglycemia, reversed the above renal functional abnormalities, reduced oxidative stress and enhanced HIF-1 alpha levels. Furthermore histological examination of kidney sections from CR diet treated diabetic rat group showed absence of glomerular hypertrophy, mesangial expansion and tubular vacoulations. Conclusion: Our results demonstrated that CR diet treatment in diabetic rats attenuated renal damage by reducing oxidative stress and preventing the development of hypoxia by up-regulating HIF-1 alpha levels.