Early mitochondrial disfunction in bromobenzene treated mice: a possible factor of liver injury.
The membrane potential of liver mitochondria isolated from bromobenzene treated mice was studied. Specifically, the efficiency of the energy-transducing mitochondrial membrane was measured during the phase between the occurrence of a massive loss of hepatic GSH, after 2-3 hr of bromobenzene intoxication, and the appearance of lipid peroxidation and cell death (12-15 hr after treatment). Partial uncoupling of oxidative phosphorylation was observed in mitochondria during the early period of intoxication (3-9 hr). These anomalies in oxidative metabolism did not result in irreversible damage to the mitochondrial inner membrane. The possibility that phenolic metabolites of bromobenzene are responsible for the uncoupling effects was examined. Orto- and especially para-bromphenol reproduced the alterations of mitochondrial function when added to normal mitochondria at concentrations comparable to those found in the livers of the intoxicated animals. Since the concentration of the bromophenols (especially p-bromophenol) largely increases after the intoxication times as tested here, mitochondrial uncoupling may represent a mechanism of liver damage acting synergistically with or even independently of other factors such as oxidative stress and lipid peroxidation.
Maellaro
E
E
Istituto di Patologia Generale dell'Università di Siena, Italy.
Del Bello
B
B
Casini
A F
AF
Comporti
M
M
Ceccarelli
D
D
Muscatello
U
U
Masini
A
A
D000410:Alanine Transaminase / Q000097:blood; D000418:Albumins / Q000494:pharmacology; D000818:Animals; D001969:Bromobenzenes / Q000378:metabolism / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology; D010636:Phenols / Q000378:metabolism
D000418:Albumins; D001969:Bromobenzenes; D010636:Phenols; D008315:Malondialdehyde; C032038:2-bromophenol; C032036:bromobenzene; D000410:Alanine Transaminase; D005978:Glutathione; C032037:4-bromophenol