Effects of arsenite treatment on NAD(P)H:quinone acceptor oxidoreductase activity in liver, lung, kidney, and heart of the rat. Comparison to induction by the polyaromatic hydrocarbon, beta-naphthoflavone

Arsenite is a potent toxin, a carcinogen, and an inducer of heat shock proteins. In this study we found that arsenite is also a novel inducer of NAD(P)H:quinone acceptor oxidoreductase (QOR) [EC 1.6.99.2] in both liver and kidney. The increases in activity were unlinked to those caused by prior trea...

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Bibliographic Details
Published inDrug metabolism and disposition Vol. 21; no. 2; p. 334
Main Authors Falkner, K C, McCallum, G P, Bend, J R
Format Journal Article
LanguageEnglish
Published United States 01.03.1993
Subjects
Animals
Arsenic - pharmacology
Arsenites
Benzoflavones - pharmacology
beta-Naphthoflavone
Cytosol - metabolism
Enzyme Induction - drug effects
Glutathione Transferase - metabolism
Male
Polycyclic Compounds - pharmacology
Quinone Reductases - biosynthesis
Rats
Rats, Sprague-Dawley
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Summary:Arsenite is a potent toxin, a carcinogen, and an inducer of heat shock proteins. In this study we found that arsenite is also a novel inducer of NAD(P)H:quinone acceptor oxidoreductase (QOR) [EC 1.6.99.2] in both liver and kidney. The increases in activity were unlinked to those caused by prior treatment with the polyaromatic hydrocarbon inducer, beta-naphthoflavone suggesting different mechanisms of induction. A single dose of sodium arsenite (75 mumol/kg sc) caused a 4-fold and 2-fold increase in activity in kidney and liver, respectively, whereas beta-naphthoflavone (60 mg/kg ip once daily for 4 days) caused a 10-fold and 4.7-fold increase in kidney and liver, respectively. This is the first study of a metalloid inducing QOR activity. Arsenite is chemically unlike any other inducer described for QOR, which include phenolic antioxidants and Michael acceptors, polyaromatic hydrocarbons, and hydrogen peroxide. Arsenite also increased glutathione S-transferase [EC 2.5.1.18] activity in rat kidney. Arsenite could be inducing QOR in liver and kidney and the glutathione S-transferase activity in kidney by an oxidant stress mechanism.
ISSN:0090-9556