Development of an experimental model for the study of hexachlorobenzene-induced hepatic porphyria in the rat.
Hexachlorobenzene (HCB) induces hepatic porphyria in rats. Various protocols of repeated cumulative and daily doses of HCB administered for several weeks until porphyria develops have been traditionally used. In order to undertake studies on early biochemical events occurring in HCB-induced porphyria, we have designed an experimental model involving the administration of a minimal amount of HCB inducing a fully developed porphyria in a well defined and predictable time frame. Groups of Sprague-Dawley rats were given (po, in 10 ml/kg of corn oil) a cumulative dose of 1,500 mg HCB/kg as 50 mg/kg for 6 weeks (5 days/week) or 100 mg/kg for 3 weeks (5 days/week). In female, but not male, rats treated for 6 weeks, HCB caused a porphyria as measured by urinary uroporphyrin and hepatic porphyrin levels; this total dose given to female rats in 3 weeks was not, however, porphyrinogenic. Female rats were given 12 consecutive daily doses of 50 mg HCB/kg followed by a no-treatment period of 30 days; this cumulative dose of 600 mg HCB/kg induced a porphyria after 6 weeks. The approximate minimally effective cumulative dose inducing porphyria was determined to be 400 mg HCB/kg, regardless of the magnitude of the daily dose (25, 50, or 100 mg/kg). Finally, the administration of a cumulative dose of 500 mg HCB/kg (50 mg/kg, 5 days/week for 2 weeks or 100 mg/kg/day for 5 days) induced after 5 to 6 weeks a porphyria that persisted for more than 500 to 600 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Krishnan
K
K
Département de médecine du travail et d'hygiène du milieu, Faculté de médecine, Université de Montréal, Québec, Canada.
Brodeur
J
J
Charbonneau
M
M
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D006581:Hexachlorobenzene / Q000633:toxicity*; D008099:Liver / Q000737:chemistry; D008107:Liver Diseases / Q000652:urine; D008297:Male; D011164:Porphyrias / Q000139:chemically induced* / Q000652:urine; D011166:Porphyrins / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D014578:Uroporphyrins / Q000652:urine
D011166:Porphyrins; D014578:Uroporphyrins; D006581:Hexachlorobenzene