Propylthiouracil attenuates acetaminophen-induced renal damage in the rat

Nephrology (Carlton). 2005 Dec;10(6):588-93. doi: 10.1111/j.1440-1797.2005.00494.x.

Abstract

Background: To date, there is no specific antidote to acetaminophen poisoning. Propylthiouracil (PTU) has been shown to be protective against acetaminophen (APAP)-induced liver damage in rats; however, the nephroprotective effect of propylthiouracil has not been studied yet.

Methods: In order to verify this, rats were given different doses of PTU (100, 200 or 400 mg/kg per body weight, orally) 1 h before a nephrotoxic dose of APAP (1,000 mg/kg per body weight, intraperitoneally (i.p.)).

Results: Propylthiouracil pretreatment significantly reduced APAP-induced nephrotoxicity in a dose-dependant manner, as evidenced by reduction in plasma creatinine and by amelioration of renal pathology (interstitial congestion, tubular cell degeneration and necrosis).

Conclusion: The mechanism of protection by PTU is probably not due to the sparing effect of non-protein thiol (approximately 95% of which is reduced glutathione), as similar depletion of renal glutathione was observed regardless of PTU pretreatment; other mechanisms are suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / toxicity*
  • Animals
  • Creatinine / blood
  • Dose-Response Relationship, Drug
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / drug therapy
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Lipid Peroxides / metabolism
  • Male
  • Propylthiouracil / therapeutic use*
  • Rats
  • Rats, Wistar
  • Sulfhydryl Compounds / metabolism
  • Urea / blood

Substances

  • Lipid Peroxides
  • Sulfhydryl Compounds
  • Acetaminophen
  • Propylthiouracil
  • Urea
  • Creatinine