Association of changes in ER stress-mediated signaling pathway with lead-induced insulin resistance and apoptosis in rats and their prevention by A-type dimeric epigallocatechin-3-gallate

Food Chem Toxicol. 2017 Dec:110:325-332. doi: 10.1016/j.fct.2017.10.040. Epub 2017 Oct 27.

Abstract

A-type dimeric epigallocatechin-3-gallate (A-type-EGCG-dimer, AEd), a new proanthocyanidins dimer from persimmon fruits, has been shown to have health benefit effects. However, A-type-EGCG-dimer affects gluose metabolism in the liver and the underlying mechanism is not clarified. The present study aims to examine the protective effects of A-type-EGCG-dimer on Pb-induced hepatic insulin resistance, endoplasmic reticulum (ER) stress and apoptosis in rats. Male wistar rats exposed to 0.05% w/v Pb acetate in the drinking water with or without A-type-EGCG-dimer coadministration (200 mg/kg body weight/day, intragastrically) for three months. We found that A-type-EGCG-dimer and pioglitazone supplementation significantly deceased glucose and insulin levels in plasma as compared with the Pb group. A-type-EGCG-dimer markedly prevents Pb-induced oxidative stress, ER stress and apoptosis in livers. A-type-EGCG-dimer and pioglitazone reduced the expression levels of the GRP78, PEPCK, G6Pase, p-PERK, p-IRE1, p-JNK, ATF4, CHOP and increased p-AKT in livers of the Pb group. Moreover, A-type-EGCG-dimer reduced ROS production and restored the activities of SOD and GPx in livers. A-type-EGCG-dimer decreased Bax, cytosolic cytochrome c and cleaved caspase-3 and increased Bcl-2 in livers of Pb-exposed rats. Our results suggest that A-type-EGCG-dimer might be a potential natural candidate for the prevention of hepatic insulin resistance and apoptosis induced by Pb.

Keywords: A-type EGCG dimer; Apoptosis; ER stress; Insulin resistance; Lead; Liver.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood Glucose / metabolism
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives*
  • Catechin / chemistry
  • Cytochromes c / metabolism
  • Dimerization
  • Diospyros / chemistry*
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress / drug effects*
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Lead / toxicity*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Metabolic Diseases / drug therapy*
  • Metabolic Diseases / metabolism
  • Metabolic Diseases / physiopathology
  • Oxidative Stress / drug effects
  • Plant Extracts / administration & dosage*
  • Plant Extracts / chemistry
  • Rats
  • Signal Transduction / drug effects*

Substances

  • Blood Glucose
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Insulin
  • Plant Extracts
  • Lead
  • Catechin
  • Cytochromes c
  • epigallocatechin gallate