Spherical neutral gold nanoparticles improve anti-inflammatory response, oxidative stress and fibrosis in alcohol-methamphetamine-induced liver injury in rats

Int J Pharm. 2018 Sep 5;548(1):1-14. doi: 10.1016/j.ijpharm.2018.06.008. Epub 2018 Jun 7.

Abstract

This study aimed to elucidate the anti-inflammatory, anti-oxidant and antifibrotic effects of gold nanoparticles (GNPs) in rats subjected to liver injury with ethanol and Methamphetamine (METH). The liver injury was induced by gavage administrations of 30% alcoholic solution (7 g/kg) once a day during 28 days, followed by METH (10 mg/kg) on the 20th and 28th days of treatment. GNPs treatment (724.96 µg/kg) during the ethanol and METH exposure was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis. Furthermore, there was a reduction in biochemical markers of liver damage and oxidative stress, and pro-inflammatory cytokines IL-1β and TNF-α, compared to ethanol + METH group alone. A decrease of FGF, SOD-1 and GPx-1 expression was also observed. GNPs down-regulated the activity of Kupffer cells and hepatic stellate cells affecting the profile of their pro-inflammatory cytokines, oxidative stress and fibrosis through modulation of signaling pathways AKT/PI3K and MAPK in ethanol + METH-induced liver injury in a rat model.

Keywords: Ethanol; Gold nanoparticles; Methamphetamine; Toxicity and Kupffer cells.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / pharmacokinetics
  • Antioxidants / therapeutic use*
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Cytokines / metabolism
  • Ethanol
  • Fibroblast Growth Factors / metabolism
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Peroxidase GPX1
  • Gold / pharmacokinetics
  • Gold / therapeutic use*
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Male
  • Malondialdehyde / metabolism
  • Metal Nanoparticles / therapeutic use*
  • Methamphetamine
  • Mice
  • NF-kappa B / genetics
  • Oxidative Stress / drug effects
  • Peroxidase / metabolism
  • RAW 264.7 Cells
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase-1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • NF-kappa B
  • Ethanol
  • Methamphetamine
  • Malondialdehyde
  • Fibroblast Growth Factors
  • Gold
  • Peroxidase
  • Glutathione Peroxidase
  • Sod1 protein, rat
  • Superoxide Dismutase-1
  • Glutathione
  • Glutathione Peroxidase GPX1