The effects of IL-18BP on mRNA expression of inflammatory cytokines and apoptotic genes in renal injury induced by infrarenal aortic occlusion

J Surg Res. 2016 May 1;202(1):33-42. doi: 10.1016/j.jss.2015.12.026. Epub 2015 Dec 22.

Abstract

Background: Renal injury is an important complication of infrarenal aortic occlusion (IAO), which is mainly encountered during the postoperative period. Aortic clamping procedure may lead to turbulent blood flow and eventually vasoconstriction at renal arterial level of the abdominal aorta. IL-18BP has well-known antioxidant and anti-inflammatory properties. In this study, we aimed to determine whether IL-18BP has anti-inflammatory, antiapoptotic, antioxidant, and protective effects on acute kidney damage induced by IAO rat model.

Materials and methods: A total of 30 adult male Wistar-Albino rats were equally and randomly separated to three groups as follows: SHAM laparotomy, ischemia-reperfusion (IR), and IR + IL-18BP. We applied 30-min IAO and 2-h reperfusion. Inflammatory cytokine levels (TNF-α, IL-1β, IL-18, IL-6, and IFN-γ) and oxidative stress parameters (TAS, TOS, and OSI) were measured. In addition to this, urea and creatinine levels, histopathology of kidney, mRNA expression levels of inflammatory cytokines, and apoptotic genes were investigated.

Results: Urea and creatinine, tissue and serum levels of TNF-α, IL-6, IL-18, IFN-γ, and TOS, and oxidative stress index (OSI) were found significantly lower in IR + IL-18BP group, when compared to the IR group. Moreover, mRNA expression levels of inflammatory cytokines and apoptotic genes were prominently depressed in IR + IL-18BP pre-treatment group in histopathologic examination, there was a significant difference between the IR and other three groups (P < 0.001). These improvements were demonstrated with a total score of histopathologic damage. In our previous studies, we have demonstrated that IL-18BP has antioxidant, inflammatory, and protective effects on liver and spinal cord IR injury. Data established from the present study suggest that IL-18BP may exert anti-inflammatory, antiapoptotic, antioxidant, and protective effects on IAO-induced acute kidney injury in rats, and this would be the first study to be conducted in this field.

Conclusions: Data established from the present study suggest that IL-18BP may exert anti-inflammatory, antiapoptotic, antioxidant, and protective effects on IAO-induced acute kidney injury in rats.

Keywords: Apoptosis; IL-18BP; Inflammation; Infrarenal aortic occlusion; Oxidative stress; Renal injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / genetics
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Aorta / surgery
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Biomarkers / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Drug Administration Schedule
  • Injections, Intraperitoneal
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Intercellular Signaling Peptides and Proteins / therapeutic use*
  • Kidney / blood supply
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Oxidative Stress / drug effects
  • Postoperative Complications / genetics
  • Postoperative Complications / metabolism
  • Postoperative Complications / prevention & control*
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / etiology
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control*
  • Treatment Outcome

Substances

  • Biomarkers
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • Protective Agents
  • RNA, Messenger
  • interleukin-18 binding protein