The minimal arsenic concentration required to inhibit the activity of thyroid peroxidase activity in vitro

Arsenical compounds are known to interfere with normal thyroid function. Therefore, we designed an experiment to determine the minimal concentration of arsenic trioxide (As2O3) required to inhibit thyroid peroxidase (TPO) activity in vitro. The activity of commercially prepared human TPO was assayed spectrophotometrically in the absence (control) or presence of arsenic (0.1, 1.0, 5.0, and 10 ppm) during a 10-min incubation period. The results of this study indicate a significant dose-response relationship with the highest concentration of arsenic producing the greatest amount of TPO inhibition. Compared to controls, 0.1 ppm arsenic had no effect on TPO activity. Incubation for 2 min in the presence of 1.0, 5.0, or 10 ppm arsenic inhibited TPO activity to 4%, 9%, and 9% of control, respectively. After 10 min incubation in the presence of 1.0 or 5.0 ppm arsenic, TPO activity returned to 92% and 54% of control, respectively, while the presence of 10 ppm arsenic further inhibited TPO activity to 1% of control. In summary, arsenic trioxide inhibits in vitro TPO activity in a dose-dependent manner, and the minimal dose required to inhibit this activity is between 0.1 and 1 ppm.