Binding of hexachlorobutadiene to alpha 2u-globulin and its role in nephrotoxicity in rats

Toxicology and Applied Pharmacology
A PählerW Dekant

Abstract

Hexachlorobutadiene (HCBD) is nephrotoxic in rats causing damage to the proximal tubules. Renal toxicity is presumed to be due to bioactivation by glutathione S-conjugate formation and further processing by the enzymes of the mercapturic acid pathway to reactive intermediates. Recent studies revealed major sex-dependent differences in the pattern of urinary metabolites and gave evidence for the excretion of unmetabolized HCBD in the urine of male, but not female, rats. The objective of this study was to investigate the basis for the excretion of unchanged HCBD in the urine. We administered [14C]-HCBD (200 mg/kg bw, po) to male and female Sprague-Dawley (SD) and NCI Black-Reiter rats (NBR), an alpha 2u-globulin-deficient strain. No major differences in the disposition and in the rates of excretion of [14C]-derived radioactivity were observed between animals of both strains. Previously observed sex-specific differences in the formation of urinary metabolites in Wistar rats were now confirmed in SD rats and were also found in NBR rats. In contrast to male SD rats, however, NBR rats did not excrete unmetabolized HCBD with urine. [14C]-HCBD (10% of total urinary metabolites) was only present in the urine of male SD rats. Anion-excha...Continue Reading

Citations

Jul 10, 2012·Expert Opinion on Drug Metabolism & Toxicology·Andrea TrevisanPatrizia Cristofori
Sep 14, 2011·Journal of Applied Toxicology : JAT·Patrizia CristoforiAndrea Trevisan
Feb 11, 2015·Cell Biology and Toxicology·Patrizia CristoforiAndrea Trevisan
Jan 26, 2005·Journal of Applied Toxicology : JAT·Andrea TrevisanEdoardo Zanetti

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