Abstract

Diabetic nephropathy is the most serious complication in diabetes mellitus. It is known that oxidative stress and inflammation play a central role in the development of diabetic nephropathy. In this study, we investigated that ferulic acid (FA) known as anti-oxidative agent could effect on diabetic nephropathy by anti-oxidative and anti-inflammatory mechanism. We examined the effects of FA in obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats. We treated FA to experimental rats from 26 to 45 weeks of age. We evaluated ACR, MDA and MCP-1 in 24 h urine and examined renal histopathology and morphologic change in extracted kidneys from rats. Also, we evaluated the ROS production and MCP-1 levels in cultured podocyte after FA treatment. In the FA-treated OLETF rats, blood glucose was significantly decreased and serum adiponectin levels were increased. Urinary ACR was significantly reduced in FA-treated OLETF rats compared with diabetic OLETF rats. In renal histopathology, FA-treated OLETF rats showed decreased glomerular basement membrane thickness, glomerular volume, and mesangial matrix expansion. FA treatment decreased oxidative stress markers and MCP-1 levels in 24 h urine of rats and supernatants of cultured podocyte. In conclusion, it was suggested that FA have protective and therapeutic effects on diabetic nephropathy by reducing oxidative stress and inflammation.

Highlights

  • Diabetic nephropathy is a major complication associated with type 2 diabetes and is a leading cause of end-stage renal disease (Kang et al, 2008)

  • We investigated the therapeutic effects of ferulic acid (FA) on oxidative stress and inflammation by characterizing morphological changes and expression changes of transforming growth factor-β1 (TGF-β1) and type IV collagen in the kidneys of type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats

  • We used OLETF rats to determine whether FA has beneficial effects in type 2 diabetic rats

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Summary

Introduction

Diabetic nephropathy is a major complication associated with type 2 diabetes and is a leading cause of end-stage renal disease (Kang et al, 2008) It is characterized functionally by proteinuria and albuminuria and pathologically by glomerular hypertrophy, mesangial expansion and tubulointerstitial fibrosis. Several growth factors or metabolic products, including transforming growth factor-β1 (TGF-β1), insulin-like growth factor-I, platelet-derived growth factor, angiotensin II, and advanced glycation end products, have been identified as contributing factors involved in the progression of diabetic glomerulopathy (Ziyadeh, 2004) Among these factors, reactive oxygen species are thought to play an important role in the development of diabetic nephropathy (Ha and Lee, 2000). It has been hypothesized that an increase in oxidative stress as a result of chronic hy-

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