Gold nanoparticles potentiates N-acetylcysteine effects on neurochemicals alterations in rats after polymicrobial sepsis

J Drug Target. 2020 Apr;28(4):428-436. doi: 10.1080/1061186X.2019.1678168. Epub 2019 Oct 17.

Abstract

Herein, we report the effect of gold nanoparticles (AuNP) and n-acetylcysteine (NAC) isolated or in association as important anti-inflammatory and antioxidant compounds on brain dysfunction in septic rats. Male Wistar rats after sham operation or caecal ligation and perforation (CLP) were treated with subcutaneously injection of AuNP (50 mg/kg) and/or NAC (20 mg/kg) or saline immediately and 12 h after surgery. Twenty-four hours after CLP, hippocampus and prefrontal cortex were obtained and assayed for myeloperoxidase (MPO) activity, cytokines, lipid peroxidation, protein carbonyls formation, mitochondrial respiratory chain, and CK activity. AuNP + NAC association decreased MPO activity and pro-inflammatory cytokines production, being more effective than NAC or AuNP isolated treatment. AuNP + NAC association and NAC isolated treatment decreased oxidative stress to lipids in both brain structures, while protein oxidation decreased only in the hippocampus of AuNP + NAC association-treated animals. Complex I activity was increased with AuNP + NAC association and NAC isolated in the hippocampus. Regarding CK activity, AuNP and AuNP + NAC association increased this marker in both brain structures after CLP. Our data provide the first experimental demonstration that AuNP and NAC association was able to reduce sepsis-induced brain dysfunction in rats by decreasing neuroinflammation, oxidative stress parameters, mitochondrial dysfunction and CK activity.

Keywords: Sepsis; brain; gold nanoparticles; n-acetylcysteine; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / metabolism*
  • Animals
  • Antioxidants / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Gold / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • Metal Nanoparticles / administration & dosage*
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Sepsis / drug therapy*
  • Sepsis / metabolism

Substances

  • Antioxidants
  • Cytokines
  • Gold
  • Peroxidase
  • Acetylcysteine