Protective effect of N-(p-amylcinnamoyl) anthranilic acid, phospholipase A2 enzyme inhibitor, and transient receptor potential melastatin-2 channel blocker against renal ischemia-reperfusion injury

J Cell Biochem. 2019 Mar;120(3):3822-3832. doi: 10.1002/jcb.27664. Epub 2018 Sep 27.

Abstract

The production of reactive oxygen species and inflammatory events are the underlying mechanisms of ischemia-reperfusion injury (IRI). It was determined that transient receptor potential melastatin-2 (TRPM2) channels and phospholipase A2 (PLA 2 ) enzymes were associated with inflammation and cell death. In this study, we investigated the effect of N-( p-amylcinnamoyl) anthranilic acid (ACA), a TRPM2 channel blocker, and PLA 2 enzyme inhibitor on renal IRI. A total of 36 male Sprague-Dawley rats were divided into four groups: control, ischemia-reperfusion (I/R), I/R + ACA 5 mg, I/R + ACA 25 mg. In I/R applied groups, the ischemia for 45 minutes and reperfusion for 24 hours were applied bilaterally to the kidneys. In the I/R group, serum levels of the blood urea nitrogen (BUN), creatinine, cystatin C (CysC), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 increased. On histopathological examination of renal tissue in the I/R group, the formation of glomerular and tubular damage was seen, and it was detected that there was an increase in the levels of malondialdehyde (MDA), caspase-3, total oxidant status (TOS), and oxidative stress index (OSI); and there was a decrease in total antioxidant capacity (TAC) and catalase enzyme activity. ACA administration reduced serum levels of BUN, creatinine, CysC, KIM-1, NGAL, interleukin-18. In the renal tissue, ACA administration reduced histopathological damage, levels of caspase-3, MDA, TOS, and OSI; and it increased the level of TAC and catalase enzyme activity. It has been shown with the histological and biochemical results in this study that ACA is protective against renal IRI.

Keywords: N-( p-amylcinnamoyl) anthranilic acid; phospholipase A2; renal ischemia-reperfusion injury; transient receptor potential melastatin-2 channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / genetics
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Antioxidants / pharmacology*
  • Blood Urea Nitrogen
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Catalase / genetics
  • Catalase / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cinnamates / pharmacology*
  • Creatinine / blood
  • Cystatin C / blood
  • Cystatin C / genetics
  • Gene Expression Regulation
  • Interleukin-18 / genetics
  • Interleukin-18 / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Lipocalin-2 / genetics
  • Lipocalin-2 / metabolism
  • Male
  • Malondialdehyde / antagonists & inhibitors
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Phospholipase A2 Inhibitors / pharmacology*
  • Phospholipases A2 / genetics*
  • Phospholipases A2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • TRPM Cation Channels / antagonists & inhibitors
  • TRPM Cation Channels / genetics*
  • TRPM Cation Channels / metabolism
  • ortho-Aminobenzoates / pharmacology*

Substances

  • Antioxidants
  • Cell Adhesion Molecules
  • Cinnamates
  • Cst3 protein, rat
  • Cystatin C
  • Havcr1protein, rat
  • Interleukin-18
  • Lcn2 protein, rat
  • Lipocalin-2
  • Phospholipase A2 Inhibitors
  • Reactive Oxygen Species
  • TRPM Cation Channels
  • Trpm2 protein, rat
  • ortho-Aminobenzoates
  • 4-amylcinnamoylanthranilic acid
  • Malondialdehyde
  • Creatinine
  • Catalase
  • Phospholipases A2
  • Casp3 protein, rat
  • Caspase 3