Reduced serum thyroid hormone levels in hexachlorobenzene-induced porphyria.
The effect of feeding 0.1% hexachlorobenzene (HCB) for 55 days on mortality, body weight, urinary porphyrin excretion, serum thyroid hormones and induction of liver microsomal enzymes was studied in female Sprague-Dawley rats. This dosage regimen, followed by 42 days of a regular diet, resulted in 33% mortality with a mean time to death of 67 +/- 4 days. Body weight of survivors was not affected by dietary HCB, whereas non-survivors underwent a rapid weight loss (wasting) prior to death. At the end of the dosing period (day 55), rats fed the HCB diet exhibited an increase in the excretion of urinary porphyrins (4-fold) and a significant decrease in the levels of serum thyroxine (T4) and triiodothyronine (T3). When rats were returned to a regular diet the excretion of urinary porphyrins continued to rise (approx. 100 times higher than controls) and serum thyroid hormones remained suppressed. At the end of the experiment (day 97), the concentration of liver microsomal cytochrome P-450 and cytochrome bs and the activity of ethoxyresorufin-O-deethylase, pentoxyresorufin-O-dealkylase, aminopyrine-N-demethylase and UDP-glucuronosyl transferase were significantly induced, whereas the activity of NADPH-cytochrome c reductase and benzo[a]pyrene hydroxylase was not. Results demonstrate that HCB-induced lethality and porphyria occur by different mechanisms, reduced T4 and T3 serum levels accompany induction of porphyria by HCB, and induction of aryl hydrocarbon hydroxylase (with benzo[a]pyrene as substrate) is not a sensitive indicator of HCB exposure.
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D002722:Chlorobenzenes / Q000633:toxicity*; D004790:Enzyme Induction; D005260:Female; D006581:Hexachlorobenzene / Q000633:toxicity*; D008107:Liver Diseases / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D011164:Porphyrias / Q000139:chemically induced* / Q000201:enzymology; D011166:Porphyrins / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*
D002722:Chlorobenzenes; D011166:Porphyrins; D014284:Triiodothyronine; D006581:Hexachlorobenzene; D013974:Thyroxine