Thyroid function and thyroxine metabolism in hexachlorobenzene-induced porphyria.
The effects of hexachlorobenzene (HCB) administration on the development of porphyria and on changes in thyroid function and thyroid hormone metabolism were examined. Female Wistar rats were treated with HCB for 1 or 8 weeks. At both treatment times liver weight was notably increased with a slight change in thyroid weight at 8 weeks. Serum thyroxine (T4) levels were depressed, whereas levels of triiodothyronine (T3) were not depressed significantly at both treatment times. One or eight weeks of HCB treatment did not alter the incorporation and distribution of [125I] into intrathyroidal aminoacids. A 50% reduction in protein bound iodine (PB[125I]) was seen in both groups of animals. HCB altered [125I]T4 metabolism in rat liver slices, increasing T4 dehalogenation. HCB administration for 1 week did not affect urinary excretion of porphyrins or their precursors, or hepatic porphyrin content. The activity of aminolaevulinate synthase was not affected, but there was a 25% and 51% inhibition in porphyrinogen carboxy-lyase (PCL) activity for the uroporphyrinogen disappearance or the coproporphyrinogen formation respectively. After 8 weeks of HCB administration the rats showed a characteristic porphyria. Our results show that HCB treatment increased hepatic thyroxine metabolism, without alterations in thyroid hormone synthesis. Serum T4 and PCL activity behaved differently in both time- and dose-dependent studies, with serum T4 being the more sensitive parameter which responded at earlier times and lower doses.
Kleiman de Pisarev
D L
DL
Departmento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Núñez, Argentina.
Rios de Molina
M C
MC
San Martin de Viale
L C
LC
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002722:Chlorobenzenes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006581:Hexachlorobenzene / Q000008:administration & dosage / Q000633:toxicity*; D007457:Iodine Radioisotopes; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011164:Porphyrias / Q000139:chemically induced*; D011166:Porphyrins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013961:Thyroid Gland / Q000187:drug effects*; D013974:Thyroxine / Q000097:blood / Q000378:metabolism*; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism*
D002722:Chlorobenzenes; D007457:Iodine Radioisotopes; D011166:Porphyrins; D014284:Triiodothyronine; D006581:Hexachlorobenzene; D000624:5-Aminolevulinate Synthetase; D013974:Thyroxine