Aurothioglucose inhibits murine thioredoxin reductase activity in vivo

Gold (I)-containing compounds, including aurothioglucose (ATG), are potent in vitro inhibitors of several selenocysteine-containing enzymes. Gold comp ounds have also been shown to potentiate the virulence of several viruses i n mice, including coxsackievirus, implicated asa possible infectious agent in Keshan disease. One possible mechanism by which gold compounds may be in creasing the virulence of viral infections in mice is by acting as a seleni um antagonist in vivo and inducing oxidative stress. To investigate the pos sible role of gold compounds in inducing oxidative stress in mice, we asses sed the ability of ATG administered in vivo to inhibit the activity of the selenocysteine-containing enzymes thioredoxin reductase (Te) and glutathion e peroxidase (GPX1). Doses as low as 0.025 mg ATG/g body weight caused sign ificant 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 wa s observed in pancreas or kidney. Because TR is involved in several importa nt cellular redox functions, its inhibition most likely will affect multipl e cellular processes. These results indicate that in vivo administration of ATG results in significant and long-lasting inhibition of TR activity. Suc h inhibition of TR could lead to increased levels of oxidative stress in vi vo, thereby increasing the virulence of several viruses including the coxsa ckievirus.