Linking the Metabolism of Hydroquinone to Its Nephrotoxicity and Nephrocarcinogenicity

  • Serrine S. Lau
  • Melanie M. C. G. Peters
  • Heather E. Kleiner
  • Patricia L. Canales
  • Terrence J. Monks
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 387)

Abstract

Hydroquinone (HQ) is nephrocarcinogenic in male Fischer-344 (F344) rats. Kari et al. (1992) described renal tubular cell degeneration in the renal cortex of male F344 rats receiving 1.8 mmol/kg HQ (13 week gavage study) and results from long-term studies demonstrated that HQ exhibited “evidence of carcinogenic activity” in male F344 rats as shown by marked increases in tubular cell adenomas of the kidneys. These findings were confirmed by Shibata et al. (1991), who reported the induction of renal cell tumors in rats following exposure to HQ in the diet (0.8%) for two years. Although the mechanism of HQ-mediated nephrocarcinogencity in male F344 rats is not known, GSH conjugates of HQ may play an important role. We have previously shown that multi-substituted glutathione (GSH) conjugates of HQ cause selective necrosis of renal proximal tubule cells in Sprague-Dawley rats when administered by intravenous injection, with 2,3,5-(triGSyl)HQ being the most potent nephrotoxicant (Lau et al., 1988). Furthermore, HQ-GSH conjugates have been identified as both in vitro and in vivo metabolites of HQ in the Sprague-Dawley rat, in quantities sufficient to propose a role for GSH conjugation in the nephrotoxicity of HQ (Hill et al., 1993). In the present study we investigated the metabolism of [14C]-HQ to HQ thioethers in the F344 rat, the rat strain used in the carcinogenicity studies, and also examined the effect of subchronic administration on the elimination and metabolic profile of [14C]-HQ. We propose that the formation of nephrotoxic metabolites may play a role in HQ-induced nephrocarcinogenicity by a mechanism that involves the generation of reactive oxygen species, oxidative DNA damage, and cytotoxicity followed by sustained hyperplasia.

Keywords

Renal Cell Tumor Potassium Bromate Renal Proximal Tubule Cell Subchronic Administration Thymine Glycol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Serrine S. Lau
    • 1
  • Melanie M. C. G. Peters
    • 1
  • Heather E. Kleiner
    • 1
  • Patricia L. Canales
    • 1
  • Terrence J. Monks
    • 1
  1. 1.Division of Pharmacology and Toxicology, College of PharmacyThe University of Texas at AustinAustinUSA

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