Renoprotective Effects of Fenofibrate via Modulation of LKB1/AMPK mRNA Expression and Endothelial Dysfunction in a Rat Model of Diabetic Nephropathy

This study was conducted to investigate whether the renoprotective effects of fenofibrate are mediated via attenuation of endothelial dysfunction and modulating the mRNA expression of adenosine monophosphate-activated protein kinase (AMPK) and its downstream kinase liver kinase B1 (LKB1) in rats wit...

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Bibliographic Details
Published in:	Pharmacology Vol. 95; no. 5-6; p. 229
Main Authors:	Al-Rasheed, Nawal M, Al-Rasheed, Nouf M, Attia, Hala A, Al-Amin, Maha A, Al-Ajmi, Hanaa N, Hasan, Iman H, Mohamad, Raeesa A, Sinjilawi, Nasr A
Format:	Journal Article
Language:	English
Published:	Switzerland 01-06-2015
Subjects:	AMP-Activated Protein Kinases - genetics Animals Blood Glucose - analysis Diabetic Nephropathies - drug therapy Diabetic Nephropathies - metabolism Diabetic Nephropathies - pathology Fenofibrate - pharmacology Fenofibrate - therapeutic use Hypolipidemic Agents - pharmacology Hypolipidemic Agents - therapeutic use Kidney - drug effects Kidney - metabolism Kidney - pathology Lipid Metabolism - drug effects Male Nitric Oxide Synthase Type III - genetics Nitrites - metabolism Protective Agents - pharmacology Protective Agents - therapeutic use Protein-Serine-Threonine Kinases - genetics Rats, Wistar RNA, Messenger - metabolism
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Summary:	This study was conducted to investigate whether the renoprotective effects of fenofibrate are mediated via attenuation of endothelial dysfunction and modulating the mRNA expression of adenosine monophosphate-activated protein kinase (AMPK) and its downstream kinase liver kinase B1 (LKB1) in rats with diabetic nephropathy (DN). Diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg kg(-1)). Fenofibrate (100 mg kg(-1), p.o.) was given to diabetic rats daily for 12 weeks. Treatment with fenofibrate significantly improved the renal function as revealed by the significant reductions in urinary albumin excretion and serum levels of creatinine and urea, in addition to the significant increase in creatinine clearance compared with the diabetic control group. Hyperglycemia-induced oxidative damage was ameliorated by treatment with fenofibrate as indicated by the significantly increased levels of glutathione and catalase together with the significant decrease in lipid peroxidation. Administration of fenofibrate caused significant increases in renal nitric oxide (NO) production and mRNA expression of endothelial NO synthase (eNOS), AMPK and LKB1, reflecting improvement of endothelial function. Our results give further insights into the mechanisms underlying the protective role of fenofibrate in DN via modulation of AMPK, LKB1 and eNOS mRNA expression.
ISSN:	1423-0313
DOI:	10.1159/000381190