Antioxidant, Antiapoptotic and Inflammatory Effects of Interleukin-18 Binding Protein on Kidney Damage Induced by Hepatic Ischemia Reperfusion

Am J Med Sci. 2016 Jun;351(6):607-15. doi: 10.1016/j.amjms.2016.02.017. Epub 2016 Mar 2.

Abstract

Objective: Acute kidney injury (AKI) is a serious condition that can be induced by liver transplantation, major hepatic resection or prolonged portal vein occlusion. The AKI can increase the frequency of postoperative complications. In the current study, we aimed to investigate whether interleukin-18 binding protein (IL-18BP) pretreatment has a protective effect against possible kidney injury-mediated liver ischemia-reperfusion (IR) achieved by Pringle maneuver in an experimental rat model.

Materials and methods: A total of 21 Wistar albino rats were included in this study. Animals were equally and randomly separated into 3 groups as follows: Sham (n = 7), IR group (n = 7) and IR + IL-18BP group (n = 7). Serum aspartate transaminase, alanine aminotransaminase and lactate dehydrogenase enzyme activities and serum urea and creatinine levels were determined. Tumor necrosis factor-α, IL-6, IL-1β, interferon gamma, total oxidant status, total antioxidant status and oxidative stress index were measured in kidney tissue homogenate samples. Histopathological examination and immunohistochemical Caspase-3 staining were applied to examine the general morphologic structure and apoptosis.

Results: Renal total oxidant status; oxidative stress index; IL-18 levels; serum aspartate transaminase, alanine aminotransaminase and lactate dehydrogenase activities and creatinine levels were significantly lower in IR + IL-18BP group, when compared with the IR group. Beside this, total antioxidant status levels were remarkably higher in IR + IL-18BP group, when compared with the IR group. The caspase-3 expression degree in IR group was remarkably higher than other groups.

Conclusions: It has been demonstrated that IL-18BP pretreatment may have inflammatory, antioxidant and antiapoptotic effects against AKI induced by hepatic IR.

Keywords: IL-18BP; Kidney injury; Liver ischemia-reperfusion injury; Protective effect; Remote organ.

MeSH terms

  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Alanine Transaminase / drug effects
  • Alanine Transaminase / metabolism
  • Animals
  • Apoptosis / drug effects*
  • Aspartate Aminotransferases / drug effects
  • Aspartate Aminotransferases / metabolism
  • Caspase 3 / drug effects
  • Caspase 3 / metabolism
  • Creatinine / metabolism
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Interferon-gamma / drug effects
  • Interferon-gamma / metabolism
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • L-Lactate Dehydrogenase / drug effects
  • L-Lactate Dehydrogenase / metabolism
  • Liver / blood supply
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • Oxidative Stress / drug effects*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / pharmacology
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / pathology
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • Urea / metabolism

Substances

  • Intercellular Signaling Peptides and Proteins
  • Interleukin-1beta
  • Interleukin-6
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • interleukin-18 binding protein
  • Interferon-gamma
  • Urea
  • Creatinine
  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Caspase 3