Remote limb ischemic preconditioning (rIPC) activates antioxidant and antiapoptotic genes and inhibits proinflammatory cytokine genes in renal ischemia/reperfusion injury

Gen Physiol Biophys. 2016 Jan;35(1):77-86. doi: 10.4149/gpb_2015035. Epub 2015 Nov 27.

Abstract

The mechanisms underlying the renoprotective effect for remote limb ischemic preconditioning (rIPC) against renal ischemia/reperfusion injury need further elucidation. In our work, one hundred and twenty male Sprague Dawley rats were randomized into 3 groups; sham, I/R group (left renal 45 min ischemia) and rIPC (as I/R group with 3 cycles of left femoral ischemic PC just before renal ischemia). Rats were sacrificed at 2 h, 24 h, 48 h and 7 days. Serum creatinine and urea were measured at the baseline and endpoints. Also, histopathological examination and assessment of the expression of inflammatory cytokines e.g. TNF-α, IL-1β and ICAM-1 and antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 in left kidney were done by the end of experiment. The results of this study demonstrated that, rIPC caused significant improvement in serum creatinine and BUN levels and in the expression of antioxidant genes and Bcl-2 antiapoptotic gene with significant attenuation of pro-inflammatory cytokines and histopathological damage score at all-time points compared to I/R group (p ≤ 0.05). In conclusion, inhibition of inflammatory cytokine (TNF-α, IL-1β and ICAM-1) formation and activation of antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 could be possible underlying mechanisms for the renoprotective effect of rIPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Apoptosis Regulatory Proteins
  • Cytokines / immunology*
  • Hindlimb / blood supply
  • Immunologic Factors / blood*
  • Ischemic Preconditioning / methods*
  • Kidney Diseases / blood
  • Kidney Diseases / physiopathology*
  • Kidney Diseases / prevention & control
  • Kidney Function Tests
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / blood
  • Reperfusion Injury / physiopathology*
  • Reperfusion Injury / prevention & control
  • Treatment Outcome

Substances

  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Cytokines
  • Immunologic Factors