INHIBITION OF H2O2 PRODUCTION BY IODOALDEHYDES IN CULTURED DOG THYROID-CELLS

2-Iodohexadecanal (IHDA) has been identified as a major thyroid iodoli pid which can be formed upon addition of iodine to the vinyl ether gro up of plasmalogens (Pereira et al., 1990). In order to test whether IH DA plays a role in the thyroid autoregulation by iodide, we have inves tigated its effects on the production of H2O2 by cultured dog thyroid cells. IHDA inhibited the formation of H2O2 in dog thyroid cells stimu lated by carbamylcholine (CCHOL). In the presence of BSA, which potent iated its action, the effect of IHDA was maximal after 2 h and had an IC50 around 5 mu M. The effect of IHDA was not decreased by methimazol e, which abolished the inhibition by iodide. IHDA also inhibited the s timulatory effect of bradykinin, but had only a marginal effect on the production of H2O2 induced by ionomycin or phorbol 12-myristate 13-ac etate (PMA). The accumulation of inositol phosphates in CCHOL-stimulat ed thyroid cells was decreased by IHDA. As evaluated by measurements o f Cr-51 release and [H-3]thymidine incorporation into DNA, IHDA had no adverse effect on thyroid cell viability. Several analogs of IHDA, of which the synthesis is described, have been tested for their inhibito ry activity. This allowed the identification of two major structural f eatures required for the biological activity: the carbonyl group at C1 and an halogen atom at C2, with iodine confering a greater activity t han bromine, while chlorine and fluorine were inactive. In conclusion, IHDA inhibits the production of H2O2 in CCHOL-stimulated dog thyroid cells by decreasing the phospholipase C cascade activity. This effect involves both the aldehyde function and the iodine atom. These results suggest that IHDA might be the mediator of some of the regulatory act ions of iodide on the thyroid gland.