Apocynin inhibited NLRP3/XIAP signalling to alleviate renal fibrotic injury in rat diabetic nephropathy

Biomed Pharmacother. 2018 Oct:106:1325-1331. doi: 10.1016/j.biopha.2018.07.036. Epub 2018 Jul 21.

Abstract

Aims: In this animal study, we tried to test the hypothesis that apocynin could play an anti-inflammation role by inhibiting NLRP3/X-linked inhibitor of apoptosis protein (XIAP) signalling and have an effect on antifibrosis in rats with diabetic nephropathy.

Main methods: Diabetic nephropathy rats were induced by tail-vein injection of streptozotocin at 60 mg/kg body weight in sodium citrate buffer (0.01 M, pH 4.5) with unrestricted access to food/water for 12 weeks, and rats with blood glucose levels above 18.0 mM were considered diabetic; the damage index for glomerular mesangial cells damage index was calculated by morphological examinations; protein and mRNA changes were analysed by western blotting immunohistochemistry and real-time quantitative polymerase chain reaction; interstitial fibrosis was assessed and scored using Masson's staining.

Key findings: In rats with diabetic nephropathy, apocynin (1) reduced renal injury and improved renal function; (2) downregulated the expression of NLRP3 in renal cortex; (3) downregulated the expression of XIAP in renal cortex; and (4) attenuated renal fibrosis.

Significance: As an inhibitor of reactive oxygen species (ROS), apocynin could downregulate the expression of NLRP3 and XIAP, and alleviate renal fibrosis, which meant not only that ROS was one type of ligands of NLRP3, but also that ROS mechanism and NLRP3 activation might be therapeutic targets in the treatment of diabetic nephropathy in the future.

Keywords: Apocynin; Diabetic nephropathy; Fibrotic injury; NLRP3/XIAP.

MeSH terms

  • Acetophenones / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology
  • Cytoprotection
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / prevention & control*
  • Fibrosis
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Kidney Cortex / drug effects*
  • Kidney Cortex / metabolism
  • Kidney Cortex / pathology
  • Kidney Cortex / physiopathology
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Oxidative Stress / drug effects
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Acetophenones
  • Anti-Inflammatory Agents
  • Antioxidants
  • Inhibitor of Apoptosis Proteins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Reactive Oxygen Species
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Xiap protein, rat
  • acetovanillone