title: Renoprotective Effects of Fenofibrate via Modulation of LKB1/AMPK mRNA Expression and Endothelial Dysfunction in a Rat Model of Diabetic Nephropathy.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Nawal M
authors.initials: NM
authors.lastname: Al-Rasheed
authors.forename: Nouf M
authors.initials: NM
authors.lastname: Al-Rasheed
authors.forename: Hala A
authors.initials: HA
authors.lastname: Attia
authors.forename: Maha A
authors.initials: MA
authors.lastname: Al-Amin
authors.forename: Hanaa N
authors.initials: HN
authors.lastname: Al-Ajmi
authors.forename: Iman H
authors.initials: IH
authors.lastname: Hasan
authors.forename: Raeesa A
authors.initials: RA
authors.lastname: Mohamad
authors.forename: Nasr A
authors.initials: NA
authors.lastname: Sinjilawi
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000235:genetics*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D009573:Nitrites / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D000960:Hypolipidemic Agents; D009573:Nitrites; D020011:Protective Agents; D012333:RNA, Messenger; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D011345:Fenofibrate