AbstractHumic substances are implicated as a kind of environmental goitrogen, and increased prevalence of goiter has been recently noticed in the blackfoot disease endemic area in the southwest of Taiwan, where well water is rich in humic substances. In this study we have investigated the effects of humic substances on hepatic 5′‐monodeiodinase (5′‐MD) in rats to gain knowledge of such effects on thyroid hormone metabolism. Aliquots of rat liver microsome (about 5 μg of protein) were preincubated in 0.1 M Tris buffer (pH 7.4) for 30 min with or without various concentrations (12.5‐800 μg/ml) of humic acids, then incubated with thyroxine (T4, 2.5 μM; final volume 1 ml) and dithiothreitol (DTT, 5 or 25 mM) in the same buffer for 30 min. The 3,5,3′‐triiodothyronine (T3) generated during incubation was quantified by radioimmunoassay (RIA) of ethanol extracts of the incubation mixture. Humic acids caused a dose‐dependent inhibition of hepatic T4 5′‐monodeiodi‐nation. The mean dose (± sd) that caused a 50 inhibition of 5′‐MD activity was 58 ± 6 μg/ml (n= 8). The inhibition was not a result of the depletion of T4 during incubation of T4 with humic acids. Free radical scavengers — catalase (300 U/ml) and superoxide dismutase (100 U/ml) — had no effect on the inhibition of hepatic T4 5′‐monodeiodination induced by humic acids. Our data suggest that humic acids influence thyroid hormone metaboli
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