Inhibition of nuclear factor-kappa B activation reduces glycerol-induced renal injury

Telma de Jesus Soares1, Roberto S Costa, Ana Paula C Balbi

  • 1Department of Physiology, School of Medicine, University of Sao Paulo at Ribeirao Preto, Ribeirao Preto, Sao Paulo, Brazil.

Journal of Nephrology
|October 19, 2006
PubMed
Abstract

Insights

Pyrrolidine dithiocarbamate (PDTC) reduces glycerol-induced kidney injury by inhibiting nuclear factor kappa B (NF-kappa B) activation and decreasing oxidative stress. This antioxidant treatment protects against renal damage and fibrosis in rats.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Toxicology

Background:

  • Glycerol injection causes acute tubular necrosis and interstitial fibrosis.
  • Oxidative stress in glycerol-treated kidneys activates the nuclear factor kappa B (NF-kappa B) pathway.
  • Mitogen-activated protein kinases (MAPKs) are also implicated in renal injury.

Purpose of the Study:

  • To investigate NF-kappa B and MAPK expression in rat renal cortex after glycerol injection.
  • To determine the relationship between NF-kappa B activation and renal structural/functional changes.
  • To evaluate the protective effects of pyrrolidine dithiocarbamate (PDTC), an NF-kappa B inhibitor, against glycerol-induced nephrotoxicity.

Main Methods:

  • Male Wistar rats received intramuscular injections of glycerol, glycerol plus PDTC, or saline.
  • Kidneys were collected at 5 and 30 days post-injection for histological and immunohistochemical analysis.
  • Plasma creatinine, fractional electrolyte excretion, urinary malondialdehyde (MDA), and cortical NF-kappa B expression were measured.

Main Results:

  • Glycerol injection increased plasma creatinine and electrolyte excretion, which were attenuated by PDTC.
  • Increased cortical expression of macrophages and NF-kappa B was observed in glycerol-treated rats.
  • PDTC treatment reduced glycerol-induced histological damage and urinary MDA levels, indicating decreased lipid peroxidation.

Conclusions:

  • PDTC attenuates glycerol-induced renal injury.
  • The protective effect of PDTC is associated with reduced NF-kappa B expression.
  • PDTC mitigates renal damage by decreasing oxidative stress and lipid peroxidation in the renal cortex.