Renoprotective Potential Of Ranolazine In Ameliorating Diabetic Nephropathy In A Rat Model Of Streptozotocin-Induced Diabetes

Abstract

Background: Diabetic nephropathy is one of the major consequences of diabetes mellitus and is defined as the progressive development
of renal insufficiency in the setting of hyperglycaemia. Poor glycaemic control, inflammation, and oxidative stress are the primary
mechanisms behind the pathogenesis of diabetic nephropathy in diabetic patients. Ranolazine is an anti-anginal drug shown antidiabetic
and anti-inflammatory effects in few preclinical and clinical trials in diabetes and coronary artery diseases. In the present study,
we aimed to investigate the renoprotecive efficacy of ranolazine in ameliorating diabetic nephropathy in a rat model of streptozotocin
induced diabetes
Methods: Male Wistar albino rats weighing 200±20 grams were used for our study. They were divided randomly into four groups of
eight. Diabetic nephropathy was induced in three groups by injecting a single dose of 45 mg/kg streptozotocin. Distilled water (normal
control), metformin 180mg/kg (metformin-treated group), and ranolazine 45mg/kg (Ranolazine treated group) were administered orally
for 8 weeks and diabetic rats in the diabetic control group remained untreated. After the administration of ranolazine, weekly random
blood glucose (RBS), HbA1c%, serum creatinine level, and urine albumin were examined. At the end of the experiment, rats were
euthanized, and the serum was analyzed for TNF-α, IL-6, and CRP levels, and kidney sections were analyzed using hematoxylin and
eosin (H & E) and PAS stain. Induction of diabetic nephropathy was confirmed by histopathological examination of the kidney.
Results: Ranolazine monotherapy significantly reduced random blood glucose(p<0.0001), HbA1c%, urine albumin, serum creatinine,
and inflammatory markers like CRP, IL-6, and TNF-α (p≤0.001) as compared to the diabetic control group. Histopathological
examination of the rat kidneys showed ranolazine was successful in preventing the changes in diabetic nephropathy such as basement
membrane thickening, mesangial matrix expansion, interstitial nephritis, and focal tubular necrosis as compared to the diabetic control
rats.
Conclusions: Ranolazine demonstrated renoprotection by significantly ameliorating diabetic nephropathy in a chronic model of
streptozotocin-induced diabetes and needs further evaluation for its use in diabetic nephropathy.