Search

Diabetic nephropathy and cardiomyopathy are two major causes of mortality among patients with diabetes mellitus (DM). Since current diabetic medications are associated with various side effects, the naturally occurring plant-derived compounds are in demand. Bioflavonoids originating from vegetables and medicinal plants have beneficial effects on diabetes by improving glycemic control, lipid metabolism, and anti-oxidant status. The present study is focused on the effect of rutin against alloxan induced diabetic nephropathy and cardiomyopathy. Male albino Wistar rats were divided into four groups, each of six rats. Group I control rats received 0.9% saline as a single dose intraperitoneally. Group II rats were induced diabetes with a single dose of alloxan monohydrate (150 mg/kg body weight in 0.9% saline) intraperitoneally. Group III rats received 0.28 M of NH 4 Cl in drinking water for 3 days for the experimental induction of metabolic acidosis. Group IV rats were injected with a single dose of alloxan monohydrate (150 mg/kg bodyweight) and administered rutin hydrate (100 mg/kg) for a period of 4 weeks by oral gavage. Administration of rutin prevented urinary ketone body formation and decreased serum creatinine and urea levels in alloxan induced diabetic rats. Rutin supplementation reduced the levels of serum triglycerides and cholesterol in diabetic rats. Gene expression profiling of metabolic acidosis related genes (AQP2, AQP3 and V2R) and also histopathological results demonstrated the protective effect of rutin against diabetic ketoacidodis and fibrosis. The results of the present study revealed rutin administration prevents the progression of diabetic nephropathy and cardiomyopathy through amelioration of fibrosis and metabolic acidosis.

Diabetic nephropathy (DN) is considered as one of the major microvascular complications of diabetes mellitus (DM) which leads to end stage renal disease (ESRD). Even though existing therapeutic options are effective in decreasing albuminuria, drugs targeting the preservation of GFR and prevention of ESRD may provide better strategy for the treatment. Since metabolic disorders are multifactorial, poly-herbal medications, and drug-herbal combination are in demand. Therefore, the present work is focused on the combinatorial renoprotective effect of rutin and ramipril on alloxan induced DN in experimental rats. Male Wistar rats were divided into five groups, group I-control, group II-diabetic rats, group III-diabetic rats treated with ramipril, group IV-diabetic rats treated with rutin, group V-diabetic rats treated with ramipril and rutin for a period of six weeks. Results revealed administration of alloxan induced hyperglycemia and alteration in antioxidant profile. However, combination of a bioflavonoid with an Angiotensin converting enzyme (ACE) inhibitor administration restored the antioxidant status in experimental DN rats. Over-expression of ACE, TGF-β1 and decreased podocin expression in diabetic rats was significantly reversed in rats administered with both ramipril and rutin. In addition to attentuating oxidative stress and fibrosis, combinatorial therapy significantly down-regulated endoplasmic reticulum stress markers GRP78 and CHOP. Notably, combination of both ramipril and rutin in low doses reduced the side effects than the administration of monotherapy alone. Histopathological results revealed that combinatorial therapy was associated with a reduction in tubulointerstitial injury. The current study contributes the understanding of the multifactorial nature of DN and implies combinatorial treatment of ACE inhibitor with an antioxidant will be a promising therapeutic strategy for DN by their mechanism of action targeting various pathophysiological changes and stress pathways., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)