In vitro effects of polyhalogenated hydrocarbons on liver mitochondria respiration and microsomal cytochrome P-450.
The present study evidenced the critical levels of six major polyhalogenated hydrocarbons (PHH's), namely chloroform, carbon tetrachloride, 1,1,1-trichloroethane, 1,2-dibromoethane,perchloroethylene, hexachlorobutadiene, over which significant inhibitory effects of the mitochondrial respiratory chain take place in vitro. At these critical levels, even in PB-induced animals only a very little fraction of cytochrome P-450 is saturated by the compounds and therefore the microsomal metabolism plays no effective role either in decreasing the levels of the test chemicals under the threshold of clear direct adverse effects in mitochondria, nor to the formation of toxic metabolites. Our data show also that phenobarbital not only enhances both the direct and metabolism-mediated interaction of most tested PHH with microsomal cytochrome P-450, but also increases the affinity of hexachlorobutadiene, chloroform and carbon tetrachloride for the mitochondrial sites resulting in respiration inhibition.
Fiorucci
L
L
Department of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanità, Rome, Italy.
Monti
A
A
Testai
E
E
Ade
P
P
Vittozzi
L
L
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology; D010101:Oxygen Consumption / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D006846:Hydrocarbons, Halogenated; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital