Unravelling the Effect of p,p'-Dichlorodiphenyldichloroethylene (DDE) in Hypertension of Wistar Rats

J Agric Food Chem. 2018 Dec 5;66(48):12847-12854. doi: 10.1021/acs.jafc.8b05001. Epub 2018 Nov 20.

Abstract

Hypertension is a multifactorial disease with limited knowledge of the involved mechanisms. p,p'-DDE ( p,p'-dichlorodiphenyldichloroethylene) is a pollutant commonly found in tissues that interferes with endocrine signaling. This study aimed to evaluate the mechanism of hypertension triggered by p,p'-DDE exposure in the presence or absence of a HF (high-fat) diet in rats. The renin-angiotensin system (RAS) was evaluated by qPCR in liver and adipose tissue (AT), and a transcriptome analysis comparing visceral AT of HF diet and HF/DDE groups was performed. HF diet influenced RAS, but the p,p'-DDE effect was more evident in liver than in AT (interaction between the diet and p,p'-DDE treatment affected aldosterone receptor and angiotensin converting enzyme 2 expression in liver, p < 0.05, two-way ANOVA). p,p'-DDE induced a decrease in the expression of genes involved in the retinoid acid biosynthesis pathway (Crabp1; -2.07-fold; p = 0.018), eNOS activation (Nos1; -1.64-fold; p = 0.012), and regulation and urea cycle (Ass1; -2.07-fold; p = 0.02). This study suggested that p,p'-DDE may play a fundamental role in the pathogenesis of hypertension, not exclusively in RAS but also by induction of hyperuricemia and increased oxidative stress, which may lead to endoplasmic reticulum stress and vascular injury.

Keywords: adipose tissue; endocrine disruptor; high-fat; liver; renin−angiotensin system.

MeSH terms

  • Animals
  • Dichlorodiphenyl Dichloroethylene / adverse effects*
  • Dichlorodiphenyl Dichloroethylene / toxicity
  • Environmental Pollutants / adverse effects*
  • Environmental Pollutants / toxicity
  • Humans
  • Hypertension / etiology*
  • Hypertension / genetics
  • Hypertension / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Mineralocorticoid / genetics
  • Receptors, Mineralocorticoid / metabolism
  • Tretinoin / metabolism

Substances

  • Environmental Pollutants
  • Receptors, Mineralocorticoid
  • Dichlorodiphenyl Dichloroethylene
  • Tretinoin
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2