PMID: 8937897Nov 1, 1996Paper

Protein arylation precedes acetaminophen toxicity in a dynamic organ slice culture of mouse kidney

Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology
D J HoivikS D Cohen

Abstract

Acetaminophen (APAP) is an analgesic and antipyretic agent which may cause hepatotoxicity and nephrotoxicity with overdose in man and laboratory animals. In vivo studies suggest that in situ activation of APAP contributes to the development of nephrotoxicity. Associated with target organ toxicity is selective arylation of proteins, with a 58-kDa acetaminophen binding protein (58-ABP) being the most prominent cytosolic target. In this study a mouse kidney slice model was developed to further evaluate the contribution of in situ activation of APAP to the development of nephrotoxicity and to determine the selectivity of protein arylation. Precision cut kidney slices from male CD-1 mice were incubated with selected concentrations of APAP (0-25 mM) for 2 to 24 hr. APAP caused a dose- and time-dependent decrease in nonprotein sulfhydryls (NPSH), ATP content, and K+ retention. Preceding toxicity was arylation of cytosolic proteins, the most prominent one being the 58-ABP. The association of 58-ABP arylation with APAP toxicity in this mouse kidney slice model is consistent with earlier, in vivo results and demonstrates the importance of in situ activation of APAP for the development of nephrotoxicity. Precision cut renal slices and dyn...Continue Reading

Citations

Mar 14, 2008·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·Maryann Mazer, Jeanmarie Perrone
Mar 31, 2010·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Sara M MolinasLaura Trumper
Feb 9, 2010·Environmental Science and Pollution Research International·Miriam HampelMichael J Leaver
Mar 26, 2003·Toxicology in Vitro : an International Journal Published in Association with BIBRA·J M CataniaA J Gandolfi
Oct 1, 1997·Toxicology in Vitro : an International Journal Published in Association with BIBRA·E B Brittebo, I Brandt
Oct 12, 2000·Toxicologic Pathology·A M LucasS D Cohen

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