The minocycline-induced thyroid pigment and several synthetic models: identification and characterization by electron paramagnetic resonance spectroscopy.

A distinctive side-effect of exposure to minocycline is black pigmentation of the thyroid gland. Previous studies have identified an association between this side-effect and the ability of minocycline to competitively inhibit thyroid peroxidase, but extensive histochemical analyses have resulted in ambiguous definitions of the pigment. Electron paramagnetic resonance spectroscopy, an especially effective technique for investigating melanins, is used in the present study to show that the thyroid pigment is well-modeled by synthetic pigments generated by oxidation of minocycline in vitro, thus indicating that it is a polymeric product due to oxidation of minocycline in vivo by thyroid peroxidase. The results demonstrate that pigments derived from minocycline comprise a novel class of pigments with redox and paramagnetic characteristics which are melanin-like in most respects yet are fundamentally unique. They also indicate that the thyroid pigment contains a large quantity of Fe bound tightly in situ, a finding with important pathophysiological implications in view of the redox properties of the pigment. The binding of Fe , however, also may provide a basis for noninvasively detecting the presence of pigmentation by magnetic resonance imaging of the thyroid. Other results of this study show that homogenizing tissues during the purification of any natural pigment can cause contamination of the pigment by extraneous metal ions and that subsequent incubation in hot acid, although most effective in removing metal ions and hydrolyzing tissue proteins, leads to degradation of melanin. By comparison, a purification procedure utilizing incubation in acid at room temperature generally is well-suited for identifying and characterizing natural melanins by electron paramagnetic resonance spectroscopy, but is inadequate for the thyroid pigment.