Preconditioning with 1,25-dihydroxyvitamin D3 protects against subsequent ischemia-reperfusion injury in the rat kidney

Nephron Exp Nephrol. 2005;100(2):e85-94. doi: 10.1159/000084574. Epub 2005 Mar 17.

Abstract

Background/aim: Induction of heat shock protein 70 (HSP70) is important in the tolerance of subsequent ischemia-reperfusion (I/R) injury. The aim of this study was to evaluate the effect of HSP70 induction by 1,25-dihydroxyvitamin D3 (VD3) on subsequent I/R injury in rats.

Methods: HSP70 was induced in Sprague-Dawley rats by VD3 treatment for 7 days, and the effect of VD3 pretreatment on subsequent I/R injury was evaluated in terms of renal function, tubular necrosis score, tumor necrosis factor alpha mRNA expression, mitogen-activated protein kinase expression, and proliferating cell nuclear antigen expression.

Results: VD3 treatment increased HSP70 expression which was localized to renal tubular cells in the outer medulla. Pretreatment with VD3 before I/R injury resulted in (1) decreased blood urea nitrogen and serum creatinine levels; (2) decreased tubular cell necrosis; (3) increased tubular cell proliferation as determined by proliferating cell nuclear antigen expression; (4) decreased tumor necrosis factor alpha mRNA expression, and (5) increased extracellular signal regulated protein kinase and decreased c-Jun N-terminal kinase expression.

Conclusion: Our study demonstrates that VD3 is a nontoxic inducer of HSP70 and exerts a protective effect against subsequent I/R injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitriol / pharmacology*
  • Calcium Channel Agonists / pharmacology*
  • HSP70 Heat-Shock Proteins / biosynthesis*
  • HSP70 Heat-Shock Proteins / physiology
  • Immunohistochemistry
  • Kidney / blood supply*
  • Kidney / pathology
  • Kidney / physiology
  • Male
  • Proliferating Cell Nuclear Antigen / analysis
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Calcium Channel Agonists
  • HSP70 Heat-Shock Proteins
  • Proliferating Cell Nuclear Antigen
  • RNA, Messenger
  • Calcitriol