Decreased enzyme activity of hepatic thioredoxin reductase and glutathione reductase in rabbits by prolonged exposure to inorganic arsenate

Chronic exposure of humans to inorganic arsenic, mainly pentavalent arsenate (iAsV), results in drinking water–induced oxidative stress (Pi et al., 2002). Thioredoxin reductase (TR) and glutathione reductase (GR) are the two critical enzymes in the response to oxidative stress in vivo. In the present study we examined alterations in enzyme activities of hepatic TR and GR from prolonged exposure of male New Zealand white rabbits to iAsV. Exposure of rabbits to iAsV in drinking water (5 mg/L) for 18 weeks caused a significant suppression of hepatic TR and GR activities, of approximately 30% and 20%, respectively, below controls. In vitro experiments suggested that trivalent inorganic arsenic (iAsIII) but not pentavalent arsenicals including iAsV, monomethylarsonic acid (MMAsV), and dimethylarsinic acid (DMAsV) affected the hepatic TR activity of rabbit. So it was suggested that in the present study iAsV ingested via drinking water was metabolized to reactive trivalent arsenicals, such as iAsIII, which may play an important role in the decreased TR and GR activities from prolonged exposure to iAsV observed in vivo. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 306–311, 2003.