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Acute sodium arsenite treatment induces Cyp2a5 but not Cyp1a1 in the C57Bl/6 mouse in a tissue (kidney) selective manner
Author(s) -
Seubert John M.,
Webb Christopher D.,
Bend John R.
Publication year - 2002
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.10023
Subject(s) - chemistry , monooxygenase , kidney , cytochrome p450 , sodium arsenite , heme oxygenase , glutathione , heme , enzyme , messenger rna , bilirubin , medicine , endocrinology , biochemistry , biology , gene , arsenic , organic chemistry
Modulation of hepatic and extrahepatic detoxication enzymes Cyp1a1, Cyp2a5, glutathione S‐transferse Ya (GSTYa) and NAD(P)H:quinone oxidoreductase (QOR) dependent catalytic activity and mRNA levels were investigated at 1, 2, or 4 days in liver, lung, or kidney of male, adult CD57 Bl/6 mice treated sc with a single dose (85 μmol/kg) of sodium arsenite (As 3+ ). Maximum decreases of total hepatic cytochrome P450 (CYP) monooxygenase content and catalytic activities, occurring at 24 h, corresponded with maximum increases of heme oxygenase (HO‐1) in all tissues, as well as maximum plasma total bilirubin. Extrahepatic increases in CYP were observed only in non‐AHR dependent isozymes in the kidney, where both Cyp2a5 mRNA and catalytic activity increased maximally 24 h after treatment. In contrast, no significant changes in Cyp2b1/2‐dependent PROD or mRNA activity and decreases in Cyp1a1‐dependent‐EROD activity were noted 1, 2, or 4 days after treatment. Increases in QOR catalytic activities were observed in all tissues examined with increased mRNA in kidney. On the other hand, GSTYa catalytic activity and mRNA increases were only detected in kidney. This study demonstrates the differential modulation of CYP, QOR, and GST‐Ya, important drug metabolizing enzymes after acute As 3+ administration. The induction of Cyp2a5, QOR, and GSTYa catalytic activity and gene expression occurred primarily in kidney during or shortly after conditions of oxidant stress. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:96–106, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/jbt.10023