Apocynin ameliorates diabetic retinopathy in rats: Involvement of TLR4/NF-κB signaling pathway

Int Immunopharmacol. 2019 Aug:73:49-56. doi: 10.1016/j.intimp.2019.04.062. Epub 2019 May 9.

Abstract

Diabetic retinopathy is a diabetes complication. During diabetic retinopathy development, the TLR4/NF-κB pathway is up-regulated. Apocynin is a nicotinamide adenine dinucleotide phosphate oxidase blocker which can reduce the superoxide radicals. It is demonstrated that apocynin can inhibit TLR4/NF-κB pathway in rats. We aim to figure out whether apocynin treatment is benefit for the diabetic retinopathy in rat model. The diabetes in rats was induced by streptozotocin. The treatment of apocynin (16 mg/kg/day) or vehicle in diabetic rat model was maintained for 12 weeks. The expression levels of relative genes in this research were shown through Western blot and qRT-PCR. Morphology of the retinas was shown by Hematoxylin-Eosin staining. The treatment of apocynin ameliorated biochemical indexes in diabetic rats and rescued the morphology of the retinas. After a 12 weeks apocynin treatment, the cell apoptosis, oxidative stress, and inflammatory in retina was reduced in diabetic rats. TLR4/NF-κB signaling pathway activity in diabetic rat retina was inhibited by apocynin. Based on our study, the treatment of apocynin ameliorates diabetic retinopathy in rats. The TLR4/NF-κB signaling pathway inhibition by apocynin is involved in this process. This result indicated a great therapeutic potential of apocynin in diabetic retinopathy treatment.

Keywords: Apocynin; Diabetic retinopathy; Nuclear factor-kappa B; Toll-like receptor 4.

MeSH terms

  • Acetophenones* / pharmacology
  • Acetophenones* / therapeutic use
  • Animals
  • Antioxidants* / pharmacology
  • Antioxidants* / therapeutic use
  • Apoptosis / drug effects
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetic Retinopathy* / drug therapy
  • Diabetic Retinopathy* / metabolism
  • Male
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Rats, Wistar
  • Retina / drug effects
  • Retina / metabolism
  • Retina / pathology
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / antagonists & inhibitors*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • Acetophenones
  • Antioxidants
  • NF-kappa B
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • acetovanillone