A combination of silymarin and garlic extract enhances thyroid hormone activation and body metabolism in orally intoxicated male rats with atrazine: Impact on hepatic iodothyronine deiodinase type 1.

Atrazine is a widely applied herbicide to improve crop yield and maintain general health. It has been reported to impair thyroid function and architecture in experimental animals. Alterations in thyroid hormones disrupt normal body function and metabolism. Silymarin, a hepatoprotective flavonolignan, was found to improve thyroid function and body metabolism. Additionally, garlic displays several protective effects on body organs. Therefore, this study explored the prophylactic impact of natural compounds comprising silymarin and garlic extract on disrupted thyroid function, hepatic iodothyronine deiodinase type 1, and metabolic parameters in atrazine-intoxicated male rats. We found that daily pre- and co-treatment of atrazine-intoxicated male rats with silymarin (100 mg/kg, p.o) and/or garlic extract (10 mg/kg, p.o) significantly improved thyroid activation and hepatic functionality as evidenced by the re-establishment of T3, T3/T4, and TSH values as well as ALT and AST activities. Interestingly, individual or concurrent supplementation of the atrazine group with silymarin and garlic extract prevented the down-regulation in hepatic iodothyronine deiodinase type 1. These effects were coupled with the repletion of serum and hepatic antioxidants and the amelioration of lipid peroxidation. In addition, current natural products markedly alleviated weight gain, dyslipidemia, hyperglycemia, glucose intolerance, and insulin resistance. Notably, a cocktail of silymarin and garlic extract exerted superior protection against atrazine-triggered deterioration of thyroid, hepatic, and metabolic functioning to individual treatments. Present findings pinpoint the prophylactic and synergistic influence of silymarin and garlic extract combinatorial regimen on thyroid activation and body metabolism via enhancing antioxidant potential, maintaining hepatic function, and iodothyronine deiodinase type 1.

Goitrogenic and estrogenic activity of soy isoflavones.

Soy is known to produce estrogenic isoflavones. Here, we briefly review the evidence for binding of isoflavones to the estrogen receptor, in vivo estrogenicity and developmental toxicity, and estrogen developmental carcinogenesis in rats. Genistein, the major soy isoflavone, also has a frank estrogenic effect in women. We then focus on evidence from animal and human studies suggesting a link between soy consumption and goiter, an activity independent of estrogenicity. Iodine deficiency greatly increases soy antithyroid effects, whereas iodine supplementation is protective. Thus, soy effects on the thyroid involve the critical relationship between iodine status and thyroid function. In rats consuming genistein-fortified diets, genistein was measured in the thyroid at levels that produced dose-dependent and significant inactivation of rat and human thyroid peroxidase (TPO) in vitro. Furthermore, rat TPO activity was dose-dependently reduced by up to 80%. Although these effects are clear and reproducible, other measures of thyroid function in vivo (serum levels of triiodothyronine, thyroxine, and thyroid-stimulating hormone; thyroid weight; and thyroid histopathology) were all normal. Additional factors appear necessary for soy to cause overt thyroid toxicity. These clearly include iodine deficiency but may also include additional soy components, other defects of hormone synthesis, or additional goitrogenic dietary factors. Although safety testing of natural products, including soy products, is not required, the possibility that widely consumed soy products may cause harm in the human population via either or both estrogenic and goitrogenic activities is of concern. Rigorous, high-quality experimental and human research into soy toxicity is the best way to address these concerns. Similar studies in wildlife populations are also appropriate.

The selenium analog of methimazole. Measurement of its inhibitory effect on type I 5'-deiodinase and of its antithyroid activity.

Methimazole (MMI), unlike propylthiouracil (PTU) is a poor inhibitor of type I iodothyronine deiodinase (ID-1). Inhibition of the enzyme by PTU was attributed initially to formation of a mixed disulfide between PTU and a cysteine residue at the active site. Presumably, MMI was unable to form a stable mixed disulfide and thus did not inhibit the enzyme. However, it has been demonstrated recently that ID-1 is a selenium-containing enzyme, with selenocysteine, rather than cysteine, at the active site. This observation raised the possibility that the selenium analog of MMI, methyl selenoimidazole (MSeI), might be a better inhibitor of ID-1 than MMI itself, as formation of the Se-Se bond with the enzyme would be expected to occur more readily than formation of the S-SE bond. To test this possibility, we developed a procedure for the synthesis of MSeI and compared MSeI with MMI and PTU for inhibition of ID-1 and for antithyroid activity. For inhibition of ID-1, MMI and MSeI were tested at concentrations of 10-300 microM. No significant inhibition was observed with MMI. MSeI showed slight but significant inhibition only in the 100-300 microM range. PTU, on the other hand, showed marked inhibition at 1 microM. Thus, replacement of the sulfur in MMI with selenium only marginally increases its inhibitory effect on ID-1. As an inhibitor of ID-1, MSeI is much less than 1% as potent as PTU. MMI and MSeI were also compared for antithyroid activity, both in vivo and in vitro. As an inhibitor of the catalytic activity of thyroid peroxidase, MMI was 4-5 times more potent than MSeI in a guaiacol assay, but only twice as potent in an iodination assay. In in vivo experiments with rats, MMI was at least 50 times more potent than MSeI in inhibiting thyroidal organic iodine formation. The relatively low potency of MSeI in vivo suggests that it is much less well concentrated by the thyroid than in MMI.