Attenuation of Renoinflammatory Cascade in Experimental Model of Diabetic Nephropathy by Sesamol

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• 作者：Anurag Kuhad ; Anand Kamal Sachdeva ; Kanwaljit Chopra
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2009
• 出版时间：July 22, 2009
• 年：2009
• 卷：57
• 期：14
• 页码：6123-6128
• 全文大小：720K
• 年卷期：v.57,no.14(July 22, 2009)
• ISSN：1520-5118

文摘

Diabetes has become the most common single cause of end-stage renal disease (ESRD) in the United States and Europe. Approximately 30−40% of patients with type I and 15% with type II diabetes mellitus develop end ESRD. The study was designed to evaluate the impact of sesamol on renal function and renoinflammatory cascade in streptozotocin (STZ)-induced diabetes. STZ-induced diabetic rats were treated with sesamol (2, 4, and 8 mg/kg/day; po) or with vehicle from the fifth to eighth weeks. After 8 weeks, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine, and urea clearance were measured. Cytoplasmic and nuclear fractions of kidney were prepared for the quantification of oxidative-nitrosative stress (lipid peroxidation, superoxide dismutase, catalase, nonprotein thiols, total nitric oxide), tumor necrosis factor-alpha (TNF-α), tissue growth factor-1 beta (TGF-β1), p65 subunit of NFκβ, and caspase-3. After 8 weeks of STZ injection, the rats produced significant alteration in renal function, increased oxidative−nitrosative stress, TNF-α, TGF-β1, caspase-3 activity in cytoplasmic lysate, and active p65 subunit of NFκβ in nuclear lysate of kidney of diabetic rats. Interestingly, co-administration of sesamol significantly and dose-dependently prevented biochemical and molecular changes associated with diabetes. Moreover, diabetic rats treated with insulin−sesamol combination produced more pronounced effect on molecular parameters as compared to their respective groups. The data reveal that sesamol modulates the release of profibrotic cytokines, oxidative stress, ongoing chronic inflammation, and apoptosis and thus exerts a marked renoprotective effect.