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Aurothioglucose Inhibits Murine Thioredoxin Reductase Activity In Vivo

Manuscript received 10 July 1998. Initial reviews completed 23 July 1998. Revision accepted 21 October 1998.

Allen D. Smith, Catherine A. Guidry, Virginia C. Morris, and Orville A. Levander

U.S. Department of Agriculture, Beltsville Human Nutrition Research Center, Nutrient Requirements and Functions Laboratory, Beltsville, MD 20705

Gold (I)-containing compounds, including aurothioglucose (ATG), are potent in vitro inhibitors of several selenocysteine-containing enzymes. Gold compounds have also been shown to potentiate the virulence of several viruses in mice, including coxsackievirus, implicated as a possible infectious agent in Keshan disease. One possible mechanism by which gold compounds may be increasing the virulence of viral infections in mice is by acting as a selenium antagonist in vivo and inducing oxidative stress. To investigate the possible role of gold compounds in inducing oxidative stress in mice, we assessed the ability of ATG administered in vivo to inhibit the activity of the selenocysteine-containing enzymes thioredoxin reductase (TR) and glutathione peroxidase (GPX1). Doses as low as 0.025 mg ATG/g body weight caused significant and prolonged inhibition of TR activity in all tissues examined. No such inhibition of GPX1 activity was seen, indicating differential in vivo sensitivity of the enzymes to inhibition by ATG. In liver and heart, some recovery of TR activity was observed after a 7-d period, but no recovery was observed in pancreas or kidney. Because TR is involved in several important cellular redox functions, its inhibition most likely will affect multiple cellular processes. These results indicate that in vivo administration of ATG results in significant and long-lasting inhibition of TR activity. Such inhibition of TR could lead to increased levels of oxidative stress in vivo, thereby increasing the virulence of several viruses including the coxsackievirus.

Key words: thioredoxin reductase, glutathione peroxidase, aurothioglucose, selenium, mice.

The Journal of Nutrition Vol. 129 No. 1 January 1999, pp. 194-198
Copyright ©1999 by the American Society for Nutritional Sciences




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