Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 387, Issue 10, pp 969–978

What is the role of renin inhibition during rat septic conditions: preventive effect of aliskiren on sepsis-induced lung injury

  • Erol Akpinar
  • Zekai Halici
  • Elif Cadirci
  • Yasin Bayir
  • Emre Karakus
  • Muhammet Calik
  • Atilla Topcu
  • Beyzagul Polat
Original Paper

DOI: 10.1007/s00210-014-1014-0

Cite this article as:
Akpinar, E., Halici, Z., Cadirci, E. et al. Naunyn-Schmiedeberg's Arch Pharmacol (2014) 387: 969. doi:10.1007/s00210-014-1014-0

Abstract

Sepsis and sepsis-related acute lung injuries (ALIs) are one of the main causes of death among hospitalized patients. Renin–angiotensin–aldosterone system (RAAS) has been reported to have role in sepsis. However, there is no study on aliskiren, a renin inhibitor, on sepsis-induced ALI. We aimed to investigate the potential protective effects of aliskiren in a model of cecal ligation and puncture (CLP)-induced lung injury. The rats were separated into five groups: sham, CLP, CLP + aliskiren 50 mg/kg (per orem (p.o.)), CLP + aliskiren 100 mg/kg (p.o.), and sham + aliskiren 100 mg/kg (p.o.). CLP model was applied via ligation of cecum and two punctures. After experiment, biochemical, molecular, and pathologic examinations were performed on lung and serum samples of rats. In our study, sepsis decreased superoxide dismutase (SOD) and glutathione (GSH) and increased malondialdehyde (MDA) in lung tissues of rats while aliskiren increased the SOD and GSH and decreased MDA. Also, sepsis caused a significant increase in pro-inflammatory cytokine levels (TNF-α, IL-1β, and IL-6) while aliskiren administration decreased these cytokines. Also, aliskiren administration at high dose protected lungs in pathologic evaluation. As a result of RAAS inhibition, aliskiren caused a decrease in serum angiotensin II level and increase in serum renin level. In light of these observations, we can suggest that the therapeutic administration of aliskiren prevented oxidative stress changes and cytokine changes and also protected lung tissues during CLP-induced sepsis by changing status of RAAS.

Keywords

Aliskiren Angiotensin II Cytokines Lung injury Oxidative stress Sepsis 

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Erol Akpinar
    • 1
  • Zekai Halici
    • 1
  • Elif Cadirci
    • 2
  • Yasin Bayir
    • 3
  • Emre Karakus
    • 4
  • Muhammet Calik
    • 5
  • Atilla Topcu
    • 1
  • Beyzagul Polat
    • 2
  1. 1.Department of PharmacologyAtaturk University Faculty of MedicineErzurumTurkey
  2. 2.Department of PharmacologyAtaturk University Faculty of PharmacyErzurumTurkey
  3. 3.Department of BiochemistryAtaturk University Faculty of PharmacyErzurumTurkey
  4. 4.Department of Pharmacology and ToxicologyAtaturk University Faculty of Veterinary MedicineErzurumTurkey
  5. 5.Department of PathologyAtaturk University Faculty of MedicineErzurumTurkey