Coexposure of lead- and lipopolysaccharide-induced liver injury in rats: involvement of nitric oxide-initiated oxidative stress and TNF-alpha

Shock. 2005 Apr;23(4):360-4. doi: 10.1097/01.shk.0000158116.77328.1d.

Abstract

In this study, we investigated the interaction between lipopolysaccharide (LPS) and lead (Pb) and the involvement of tumor necrosis factor-alpha (TNF-alpha) and oxidative stress in Pb-plus-LPS (Pb/LPS)-induced liver damage in rats. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-alpha, nitric oxide (NO), and lipid peroxidation (LPO) were determined in rats treated with Pb and/or LPS. Pb ranging from 0 to 15 mg/kg dose dependently increased AST, ALT, NO, or LPO in LPS-treated rats. Pretreatment with iNOS inhibitor 1400W reduced NO, LPO, TNF-alpha, AST, and ALT in Pb/LPS-treated rats. Thus, Pb increased LPS-induced liver damage, which might be associated with increased NO-initiated oxidative stress and TNF-alpha in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Amidines / pharmacology
  • Animals
  • Aspartate Aminotransferases / blood
  • Benzylamines / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Lead / metabolism
  • Lead / pharmacology
  • Lead / toxicity*
  • Lipid Peroxidation
  • Lipopolysaccharides / blood
  • Lipopolysaccharides / pharmacology
  • Lipopolysaccharides / toxicity*
  • Liver / drug effects*
  • Liver / injuries*
  • Male
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Nitrites / blood
  • Organometallic Compounds / pharmacology
  • Oxidative Stress*
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Amidines
  • Benzylamines
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • N-(3-(aminomethyl)benzyl)acetamidine
  • Nitrites
  • Organometallic Compounds
  • Tumor Necrosis Factor-alpha
  • Lead
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • lead acetate