Abstract

The study aimed to explore the prophylactic effect of melatonin, rowatinex; a naturally occurring renal drug, and its combination on diabetic nephropathy in type 2 diabetic rats. Diabetes was induced by intraperitoneal injection of a single dose of streptozotocin (50 mg/g body weight). Three days before diabetes induction, rats were daily treated with melatonin, rowatinex and their combination continuously for 8 weeks. Evaluation was done through measuring blood urea nitrogen (BUN), serum uric acid, serum creatinine, urine creatinine, creatinine clearance, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), total antioxidant capacity (TAC), kidney injury molecule-1 (KIM-1), heat shock protein-70 (HSP-70), caspase-3, transforming growth factor β1 (TGFβ1), DNA degradation by the comet assay and total protein contents. Histopathologic study was also done for the kidney and the pancreas. Drastic changes in all measured parameters of the diabetic rats were observed. Treatment with melatonin and rowatinex showed amelioration to variable degrees. In conclusion, melatonin showed the most potent effect on protecting rats from deleterious action of diabetic nephropathy followed by its combination with rowatinex.

Highlights

  • Diabetes is a disease with many complications and characterized by chronic hyperglycemia that may lead to microvascular complications, including nephropathy and macrovascular complications if left untreated[1]

  • Concerning body weight, diabetic rats showed a significant decrease by 17.40% as compared with the normal control rats

  • Loss of body weight and high blood glucose level were observed in our study

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Summary

Introduction

Diabetes is a disease with many complications and characterized by chronic hyperglycemia that may lead to microvascular complications, including nephropathy and macrovascular complications if left untreated[1]. Increase in type IV collagen and decrease in heparan sulfate (HS) are known to take place[3]. Type IV collagen is one of the constituents of the extracellular matrix (ECM) in the glomerular basement membrane (GBM) that provides a scaffold for other ECM components by its network-like structure[3]. The thickening of GBM and the alteration of its composition during diabetic nephropathy lead to abnormal filtration[4]. Melatonin (N-acetyl-5-methoxytryptamine) is a pineal gland hormone. It has a variety of physiologic, immunological and biochemical functions. It is an endogenous free-radical scavenger and exerts chemoprotective, immunostimluatory and myelostimulatory effects[8], which are important in the treatment of

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