Amlodipine- and valsartan-enhanced end-organ protection in Streptozotocin-Induced Type 2 diabetic rats treated with metformin

Abstract

Effective prevention of multiple end organ damage (MEOD), the hallmark complication and major cause of mortality in unresolved or poorly managed  type 2 diabetes mellitus (T2DM), is critical for prolongation of life in T2DM sufferers. We hypothesize that known organ-protective normotensive drugs  prevent MEOD hence improve treatment outcomes in diabetic patients. As a result, this study aimed at the histological evaluation of the effects of  amlodipine and valsartan on metformin-treated streptozotocin-induced T2DM rats. Male Wistar rats weighing 200 g - 350 g were fasted overnight and  diabetes mellitus (DM) was induced with a single dose of 40 mg/kg of streptozotocin administered intraperitoneally. Fasting blood sugar was determined  after 48 hrs and rats with fasting blood sugar ≥ 200 mg/dl were considered diabetic. Healthy and diabetic rats were selected into treatment groups  (group1: healthy rats - normal control; group 2: untreated diabetic rats; groups 3-5: diabetic rats treated with metformin, metformin plus amlodipine, and  metformin plus valsartan respectively). The rats were sacrificed under chloroform anaesthesia after six weeks of treatment. Key visceral organs  (heart, lung, liver, and kidney) were excised, and histopathological examination was carried out on them. There are histologic evidence of improved organ  protection in rats treated with amlodipine and valsartan as adjunct treatment with metformin. Our findings show that addition of anti hypertensive  drugs (amlodipine and valsartan) to metformin improved treatment outcomes in diabetic rats compared to when the metformin was  used alone.