Evaluation of Levothyroxine Bioavailability after Oral Administration of a Fixed Combination of Soy Isoflavones in Post-menopausal Female Volunteers.

BACKGROUND: Post-menopausal women under treatment with levothyroxine for their medical conditions may take concomitantly dietary supplements containing soy isoflavones in combination to treat their post-menopausal symptoms. The aim of this study was to investigate the effect of a fixed combination of soy isoflavones on the oral bioavailability of levothyroxine in post-menopausal female volunteers. METHODS: 12 healthy post-menopausal female, who were on stable oral levothyroxine as replacement/supplementation therapy for hypothyroidism, received a single recommended oral dose of a food supplement containing 60 mg of soy isoflavones (>19% genistin and daidzin) concomitantly with (test) and 6 h later (reference) the administration of levothyroxine in a randomized, open label, crossover fashion. Plasma concentrations of levothyroxine and soy isoflavones (daidzin, daidzein, genistin, genistein, S-equol) were determined by LC-MS/MS. Pharmacokinetic (PK) parameters were determined by non-compartmental analysis. No effect of soy isoflavones was assumed if the 90% confidence intervals (CIs) for the estimated ratio test/reference was included in the acceptance limits 0.80-1.25 for PK parameters Cmax and AUCt. RESULTS: The test/reference ratios Cmax and AUCt of levothyroxine were very close to unity (1.02 and 0.99, respectively) and the corresponding 90% CIs (0.99-1.04 and 0.88-1.12, respectively) fell entirely within the acceptance bioequivalence limits. CONCLUSION: The combination of soy isoflavones used in the present investigation does not affect the rate and extent of levothyroxine absorption when administered concomitantly in post-menopausal women.

Porphyromonas gingivalis infection sequesters pro-apoptotic Bad through Akt in primary gingival epithelial cells.

Porphyromonas gingivalis, a self-limiting oral pathogen, can colonize and replicate in gingival epithelial cells (GECs). P. gingivalis-infected GECs are protected from mitochondrion-dependent apoptosis, partially through activation of phosphatidyl inositol 3-kinase/Akt signaling. Biochemical events associated with P. gingivalis-induced inhibition of apoptosis include the blocking of mitochondrial membrane permeability and cytochrome-c release. We studied functional importance of Akt and the status of associated key mitochondrial molecules, pro-apoptotic Bad and caspase-9, during infection of GECs. We found that P. gingivalis infection caused significant phosphorylation of Bad progressively, while messenger RNA levels for Bad slowly decreased. Fluorescence microscopy showed translocation of the mitochondrial Bad to the cytosol post-infection. Conversely, P. gingivalis lost the ability to promote phosphorylation and translocation of Bad in Akt-deficient GECs. Caspase-9 activation induced by a chemical inducer of apoptosis was significantly inhibited by infection over time. However, Akt depletion by small interfering RNA did not reverse inhibition of caspase-9 activation by infection. Hence, P. gingivalis inactivates pro-apoptotic Bad through Akt. The inhibition of caspase-9 activation appears to be independent of Akt. Overall, our findings suggest that Akt is a key component of anti-apoptotic pathways stimulated by P. gingivalis. The P. gingivalis uses other mitochondrial pathways to protect host cells from cell-death and to ensure its survival in gingival epithelium.