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 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.
Falkner
K C
KC
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.
McCallum
G P
GP
Bend
J R
JR
D000818:Animals; D001151:Arsenic / Q000494:pharmacology*; D018053:Arsenites; D001571:Benzoflavones / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011808:Quinone Reductases / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019324:beta-Naphthoflavone
D018053:Arsenites; D001571:Benzoflavones; D011083:Polycyclic Compounds; D019324:beta-Naphthoflavone; C041831:NADH dehydrogenase (quinone); D011808:Quinone Reductases; D005982:Glutathione Transferase; C015001:arsenite; D001151:Arsenic