Effect of lead acetate on cytosolic thioredoxin reductase activity and oxidative stress parameters in rat kidneys

Basic Clin Pharmacol Toxicol. 2007 Aug;101(2):96-100. doi: 10.1111/j.1742-7843.2007.00084.x.

Abstract

Oxidative stress has been suggested to be an important molecular mechanism of toxic effects of lead in the kidney. Thioredoxin reductase-1 is a selenoprotein involved in many cellular redox processes. This study evaluated the effect of acute and chronic exposure intraperitoneally to lead acetate on thioredoxin reductase-1 activity and on other oxidative stress parameters in the rat kidney, as well as on indicators of renal function commonly used to assess lead poisoning. Acute exposure to 25 mg/kg lead acetate increased superoxide dismutase and thioredoxin reductase-1 activity (after 6, 24 and 48 hr), while exposure to 50 mg/kg lead acetate increased catalase activity (after 48 hr) and inhibited delta-aminolevulinate dehydratase activity (after 6, 24 and 48 hr) in the kidney (P < 0.05). Chronic exposure (30 days) to 5 mg/kg lead acetate inhibited delta-aminolevulinate dehydratase and increased glutathione S-transferase, non-protein thiol groups, catalase, thioredoxin reductase-1 and uric acid plasma levels, while exposure to 25 mg/kg lead acetate reduced body weight and delta-aminolevulinate dehydratase, but increased glutathione S-transferase, non-protein thiol groups and uric acid plasma levels (P < 0.05). No changes were observed in thiobarbituric acid reactive substances, glutathione peroxidase, creatinine or inorganic phosphate levels after either acute or chronic exposure. Our results suggest that thioredoxin reductase-1 may be an early indicator of acute exposure to low lead doses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Creatinine / blood
  • Dose-Response Relationship, Drug
  • Kidney / drug effects*
  • Kidney / enzymology
  • Kidney Function Tests
  • Male
  • Organometallic Compounds / pharmacology*
  • Oxidative Stress / drug effects*
  • Porphobilinogen Synthase / drug effects
  • Porphobilinogen Synthase / metabolism
  • Rats
  • Rats, Wistar
  • Thioredoxin Reductase 1
  • Thioredoxin-Disulfide Reductase / drug effects*
  • Thioredoxin-Disulfide Reductase / metabolism
  • Uric Acid / blood

Substances

  • Organometallic Compounds
  • Uric Acid
  • Creatinine
  • Thioredoxin Reductase 1
  • Thioredoxin-Disulfide Reductase
  • Txnrd1 protein, rat
  • Porphobilinogen Synthase
  • lead acetate