Renoprotective effects of fenofibrate via modulation of LKB1/AMPK mRNA expression and endothelial dysfunction in a rat model of diabetic nephropathy

Nawal M. Al-Rasheed, Nouf M. Al-Rasheed, Hala A. Attia, Maha A. Al-Amin, Hanaa N. Al-Ajmi, Iman H. Hasan, Raeesa A. Mohamad, Nasr A. Sinjilawi

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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.

Original languageEnglish
Pages (from-to)229-239
Number of pages11
JournalPharmacology
Volume95
Issue number5-6
DOIs
Publication statusPublished - 1 Dec 2015

Fingerprint

Fenofibrate
Diabetic Nephropathies
Adenosine Monophosphate
Protein Kinases
Phosphotransferases
Messenger RNA
Liver
Creatinine
Kidney
Nitric Oxide Synthase Type III
Streptozocin
Intraperitoneal Injections
Serum Albumin
Nitric Oxide Synthase
Hyperglycemia
Catalase
Lipid Peroxidation
Glutathione
Urea
Nitric Oxide

Keywords

  • Adenosine monophosphate-activated protein kinase
  • Diabetic nephropathy
  • Endothelial nitric oxide synthase
  • Fenofibrate
  • Liver kinase B1
  • Oxidative stress

Cite this

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. / Renoprotective effects of fenofibrate via modulation of LKB1/AMPK mRNA expression and endothelial dysfunction in a rat model of diabetic nephropathy. In: Pharmacology. 2015 ; Vol. 95, No. 5-6. pp. 229-239.
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Renoprotective effects of fenofibrate via modulation of LKB1/AMPK mRNA expression and endothelial dysfunction in a rat model of diabetic nephropathy. / 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.

In: Pharmacology, Vol. 95, No. 5-6, 01.12.2015, p. 229-239.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Renoprotective effects of fenofibrate via modulation of LKB1/AMPK mRNA expression and endothelial dysfunction in a rat model of diabetic nephropathy

AU - Al-Rasheed, Nawal M.

AU - Al-Rasheed, Nouf M.

AU - Attia, Hala A.

AU - Al-Amin, Maha A.

AU - Al-Ajmi, Hanaa N.

AU - Hasan, Iman H.

AU - Mohamad, Raeesa A.

AU - Sinjilawi, Nasr A.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

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KW - Endothelial nitric oxide synthase

KW - Fenofibrate

KW - Liver kinase B1

KW - Oxidative stress

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DO - 10.1159/000381190

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SP - 229

EP - 239

JO - Pharmacology

JF - Pharmacology

SN - 0031-7012

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