Thyroxine pretreatment and halothane administration alter Ca2+ transport and transmembrane potential in rat liver mitochondria. An additional mechanism for halothane-induced liver damage in the hyperthyroid rat model.
Male rats pretreated with thyroid hormones and exposed to halothane in non-hypoxic conditions develop acute liver damage. In order to investigate the mechanisms leading to liver damage in this animal model, the effects of thyroxine (T4) pretreatment and halothane administration on Ca2+ transport and transmembrane potential were studied in isolated rat liver mitochondria. Five-day T4-pretreatment reduced the mitochondrial Ca2+ loading capacity and increased the rate of Ca2+ cycling across the mitochondrial membrane. Halothane administration further increased Ca2+ cycling and produced a time- and dose-dependent loss of transmembrane potential which was more pronounced in mitochondria from T4-pretreated rats than in euthyroid animals. When mitochondria from T4-pretreated rats were incubated in the presence of the Ca2+ chelator EGTA, membrane potential was well preserved. In contrast, when Ca2+ concentration in the extramitochondrial medium was increased, mitochondria deenergization occurred earlier. These findings confirm that alterations in Ca2+ transport and mitochondrial function can be interrelated events and suggest that a Ca(2+)-dependent, halothane-induced loss of transmembrane potential could participate in generating acute liver damage in hyperthyroid rats exposed to halothane in non-hypoxic conditions.
Imberti
R
R
Servizio di Anestesia e Rianimazione II, IRCCS Policlinico S. Matteo, Pavia, Italy.
Vairetti
M
M
Richelmi
P
P
Preseglio
I
I
Bellomo
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006221:Halothane / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000008:administration & dosage / Q000494:pharmacology*
D013974:Thyroxine; D002118:Calcium; D006221:Halothane