Proanthocyanidins improves lead-induced cognitive impairments by blocking endoplasmic reticulum stress and nuclear factor-κB-mediated inflammatory pathways in rats

Food Chem Toxicol. 2014 Oct:72:295-302. doi: 10.1016/j.fct.2014.07.033. Epub 2014 Jul 31.

Abstract

Proanthocyanidins (PCs), a class of naturally occurring flavonoids, had been reported to possess a variety of biological activities, including anti-oxidant, anti-tumor and anti-inflammatory. In this study, we examined the protective effect of PCs against lead-induced inflammatory response in the rat brain and explored the potential mechanism of its action. The results showed that PCs administration significantly improved behavioral performance of lead-exposed rats. One of the potential mechanisms was that PCs decreased reactive oxygen species production and increased the total antioxidant capacity in the brains of lead-exposed rats. Furthermore, the results also showed that PCs significantly decreased the levels of tumor necrosis factor-α, interleukin 1β and cyclooxygenase-2 in the brains of lead-exposed rats. Moreover, PCs significantly decreased the levels of beta amyloid and phosphorylated tau in the brains of lead-treated rats, which in turn inhibited endoplasmic reticulum (ER) stress. PCs also decreased the phosphorylation of protein kinase RNA-like ER kinase, eukaryotic translation initiation factor-2, inositol-requiring protein-1, c-Jun N-terminal kinase, p38 and inhibited nuclear factor-κB nuclear translocation in the brains of lead-exposed rats. In conclusion, these results suggested that PCs could improve cognitive impairments by inhibiting brain oxidative stress and inflammatory response.

Keywords: Beta amyloid; Brain inflammation; Endoplasmic reticulum stress; Lead; Oxidative stress; Proanthocyanidins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Behavior, Animal / drug effects
  • Cognition Disorders / chemically induced
  • Cognition Disorders / pathology*
  • Cyclooxygenase 2 / metabolism
  • Endoplasmic Reticulum Stress / drug effects*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Interleukin-1beta / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lead / toxicity*
  • Lipid Peroxidation / drug effects
  • Male
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism
  • NF-kappa B / metabolism
  • Neuroprotective Agents / pharmacology*
  • Phosphorylation / drug effects
  • Proanthocyanidins / pharmacology*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Interleukin-1beta
  • Membrane Proteins
  • NF-kappa B
  • Neuroprotective Agents
  • Proanthocyanidins
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • tau Proteins
  • Lead
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Ern2 protein, rat
  • Protein Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases