Tert-butylhydroquinone attenuates oxidative stress and inflammation in hypothalamic paraventricular nucleus in high salt-induced hypertension

Toxicol Lett. 2017 Nov 5:281:1-9. doi: 10.1016/j.toxlet.2017.08.018. Epub 2017 Aug 24.

Abstract

Excessive oxidative stress and inflammation in hypothalamic paraventricular nucleus (PVN) are implicated in the pathogenesis of hypertension. It is reported that tert-butylhydroquinone (tBHQ), a nuclear factor erythroid 2-related factor 2(Nrf2)-inducer, has a variety of pharmacological activities such as anti-oxidation and anti-inflammatory effect. The objective of this study was to investigate the effects of tBHQ in high salt induced hypertension and to identify whether the beneficial effects were induced by inhibiting PVN oxidative stress and inflammation. Male Sprague-Dawley rats were fed with high salt diet (HS, 8% NaCl) or normal salt diet (NS, 0.3% NaCl). These rats were administration of tBHQ (150mg/kg/d) by oral gavage for 16 weeks. Our results showed that high salt intake resulted in higher mean arterial pressure, cardiac hypertrophy as well as increased plasma level of norepinephrine and interleukin (IL)-1β, IL-6 compared with NS rats. It increased PVN level of reactive oxygen species, gp91phox, IL-1β, IL-6, p-IKKβ and nuclear factor-kappa B (NF-κB) activity, decreased PVN level of Nrf2 and Cu/Zn-SOD. Chronic administration of tBHQ significantly attenuated these changes in HS rats. These data suggest that the protective effects of tBHQ in salt induced hypertension are partly due to inhibiting oxidative stress and inflammation in PVN.

Keywords: Hypertension; Hypothalamic paraventricular nucleus; Inflammation; Oxidative stress; Tert-butylhydroquinone.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Arterial Pressure
  • Disease Models, Animal
  • Hydroquinones / pharmacology*
  • Hypertension / chemically induced
  • Hypertension / drug therapy*
  • Inflammation / drug therapy*
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Male
  • Membrane Glycoproteins / blood
  • NADPH Oxidase 2
  • NADPH Oxidases / blood
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Norepinephrine / blood
  • Oxidative Stress / drug effects*
  • Paraventricular Hypothalamic Nucleus / drug effects*
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Sodium Chloride, Dietary / administration & dosage
  • Sodium Chloride, Dietary / adverse effects*
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Hydroquinones
  • Interleukin-1beta
  • Interleukin-6
  • Membrane Glycoproteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Reactive Oxygen Species
  • Sodium Chloride, Dietary
  • 2-tert-butylhydroquinone
  • Superoxide Dismutase
  • Cybb protein, rat
  • NADPH Oxidase 2
  • NADPH Oxidases
  • Norepinephrine