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A Qualitative Comparison of Porcine and Rodent Thyroperoxidase -Effects of Environmental Chemicals.
Citation:
HEDGE, J. M., K. M. CROFTON, K. R. Grant, AND K. B. Paul. A Qualitative Comparison of Porcine and Rodent Thyroperoxidase -Effects of Environmental Chemicals. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
A wide variety of environmental chemicals act on a number of animal species as thyroid disruptors. Thyroperoxidase (TPO) is one of the known targets for many of the thyroid disrupting chemicals (TDC). The majority of the in vivo toxicological research on TDCs is conducted in rats whereas most TPO research is conducting using thyroid microsomes collected from pigs . This work compares the sensitivity of porcine and rodent microsomes for the detection of TPO inhibition using a varie of known thyroid inhibitors.
Description:
A wide variety of environmental chemicals alter the function of the thyroid system in many animal species. Thyroperoxidase (TPO), the enzyme that synthesizes thyroid hormone, is one of the known biochemical targets for thyroid disrupting chemicals (TDC). The majority of the in vivo toxicological research on TDCs is conducted in rats whereas most TPO research has been conducted using porcine thyroid microsomes. The sensitivity of porcine and rodent microsomes for TPO inhibition using known TDCs and chemicals of unknown activity was compared to establish the species concordance. Microsomes were isolated from rat and pig thyroid glands and the TPO assay was performed based on the guaiacol oxidation method. Concentration response curves were derived for the following chemicals: methimazole (MMZ); dibutylphthalate; diethylhexylphthalate; diethylphthalate; Triclosan; pnonylphenol; 6-propylthiouracil (PTU); sodium perchlorate (PERC); iopanoic acid, 4-propoxylphenol (4POP); 5,5-dimethylpyrazole-l-methanol (DPM) and 2-mercaptobenzothiazole (MBT). Of these tested chemicals, MMZ, PTU, MBT, DPM, 4POP and PERC inhibited TPO activity. Results demonstrate a qualitative concordance of response between the two species. All chemicals that inhibited TPO in porcine microsomes also inhibited TPO in rat microsomes. The derived IC50 values revealed slight differences in relative potency between species. MBT, PTU, and DPM exhibited greater relative potency in rats than pigs, but rank order potency for inhibition was similar with PTU>MBT>DPM>4POP=PERC. These results support the extrapolation of porcine TPO data on environmental chemicals to potential activity in in vivo rodent studies. This abstract does not necessarily reflect the policy of the US EPA.