The effect of iron overload on the mitochondrial porphyrin level in the hexachlorobenzene induced experimental porphyria.
Liver mitochondria isolated from rats treated with hexachlorobenzene plus iron, present a lower content of total porphyrin in respect to that of mitochondria from rats fed hexachlorobenzene alone. The in vitro mitochondrial porphyrin accumulation processes have been studied in mitochondria from iron loaded rats. It has been found that under these conditions the active porphyrin uptake process, which is driven by the K+ transmembrane gradient, is maximally inhibited in the presence of pentachlorophenol at a concentration similar to that found in vivo in the hexachlorobenzene experimental porphyria. By contrast the same degree of inhibition is presented by control mitochondria only in the presence of pentachlorophenol plus valinomycin, a condition which collapses the transmembrane K+ gradient. A strict correlation between porphyrin uptake and K+ concentration has been found in control as well as in iron treated mitochondria. A possible involvement of peroxidative reactions in the mitochondrial membranes has been proposed as a cause of the changes in the permeability properties of the mitochondrial membranes in the experimental chronic hepatic porphyria under conditions of iron overload.
Masini
A
A
Istituti di Chimica Biologica, Universita' di Modena, Italy.
Trenti
T
T
Ceccarelli
D
D
Muscatello
U
U
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002722:Chlorobenzenes / Q000009:adverse effects*; D005260:Female; D006581:Hexachlorobenzene / Q000009:adverse effects*; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D010416:Pentachlorophenol / Q000494:pharmacology; D011164:Porphyrias / Q000139:chemically induced / Q000378:metabolism*; D011166:Porphyrins / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014634:Valinomycin / Q000494:pharmacology
D002722:Chlorobenzenes; D011166:Porphyrins; D014634:Valinomycin; D006581:Hexachlorobenzene; D010416:Pentachlorophenol; D007501:Iron