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Molecular and Cellular Biochemistry

, Volume 453, Issue 1–2, pp 1–9 | Cite as

Estradiol attenuates ischemia reperfusion-induced acute kidney injury through PPAR-γ stimulated eNOS activation in rats

  • Amrit Pal Singh
  • Nirmal Singh
  • Devendra Pathak
  • Preet Mohinder Singh BediEmail author
Article

Abstract

We investigated the involvement of peroxisome proliferator activated receptor-γ (PPAR-γ)/endothelial nitric oxide synthase (eNOS) pathway in estradiol mediated protection against ischemia reperfusion (I/R)-induced acute kidney injury (AKI) in rats. To induce AKI, rats underwent 40 min of bilateral renal ischemia followed by 24 h of reperfusion. I/R-induced kidney damage was quantified by measuring serum creatinine, creatinine clearance, urea nitrogen, uric acid, potassium, fractional excretion of sodium, microproteinuria, and renal oxidative stress (thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione). Hematoxylin eosin stain demonstrated renal histology, while renal expression of apoptotic markers (Bcl-2, Bax), PPAR-γ and eNOS were quantified by immunohistochemistry. Estradiol (1 mg/kg, i.p.) was administered 30 min before I/R in rats. In separate groups, PPAR-γ antagonist, BADGE (30 mg/kg, i.p.), and NOS inhibitor, l-NAME (20 mg/kg, i.p.) were administered prior to estradiol treatment, which was followed by I/R in rats. I/R caused significant renal damage as demonstrated by biochemical (serum/urine), renal oxidative stress and histological changes alongwith increased expression of Bax and decreased levels of Bcl-2, PPAR-γ and eNOS, which were prevented by estradiol. Pre-treatment with BADGE and l-NAME abolished estradiol mediated renoprotection. Notably, I/R + estradiol + BADGE group revealed decreased expression of PPAR-γ and eNOS in renal tissues. In I/R + estradiol + l-NAME group, eNOS expression was reduced while PPAR-γ levels remained unchanged. These results suggest that estradiol modulates PPAR-γ which consequently regulates eNOS expression in rat kidneys. We conclude that estradiol protects against I/R-induced AKI through PPAR-γ stimulated eNOS activation in rats.

Keywords

Kidney Ischemia reperfusion Nitric oxide PPAR-γ eNOS Estradiol 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Amrit Pal Singh
    • 1
  • Nirmal Singh
    • 2
  • Devendra Pathak
    • 3
  • Preet Mohinder Singh Bedi
    • 1
    Email author
  1. 1.Department of Pharmaceutical SciencesGuru Nanak Dev UniversityAmritsarIndia
  2. 2.Department of Pharmaceutical Sciences and Drug ResearchPunjabi UniversityPatialaIndia
  3. 3.Department of Veterinary AnatomyGuru Angad Dev Veterinary and Animal Sciences UniversityLudhianaIndia

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