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

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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.

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Acknowledgments

This work was supported by the Ataturk University Medical Research Council (grant number 2011/392).

Conflict of interest

None of the authors has a commercial interest, financial interest, and/or other relationship with manufacturers of pharmaceuticals, laboratory supplies, and/or medical devices or with commercial providers of medically related services.

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Authors and Affiliations

  1. Department of Pharmacology, Ataturk University Faculty of Medicine, 25240, Erzurum, Turkey

    Erol Akpinar, Zekai Halici & Atilla Topcu

  2. Department of Pharmacology, Ataturk University Faculty of Pharmacy, Erzurum, Turkey

    Elif Cadirci & Beyzagul Polat

  3. Department of Biochemistry, Ataturk University Faculty of Pharmacy, Erzurum, Turkey

    Yasin Bayir

  4. Department of Pharmacology and Toxicology, Ataturk University Faculty of Veterinary Medicine, Erzurum, Turkey

    Emre Karakus

  5. Department of Pathology, Ataturk University Faculty of Medicine, Erzurum, Turkey

    Muhammet Calik

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  1. Erol Akpinar
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Correspondence to Zekai Halici.

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Akpinar, E., Halici, Z., Cadirci, E. et al. What is the role of renin inhibition during rat septic conditions: preventive effect of aliskiren on sepsis-induced lung injury. Naunyn-Schmiedeberg's Arch Pharmacol 387, 969–978 (2014). https://doi.org/10.1007/s00210-014-1014-0

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