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 (T-4) pretreatment and halothane administration on Ca2+ transport and transmembrane potential were studied in isolated rat liver mitochondria. Five-day T-4-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 T-4-pretreated rats than in euthyroid animals. When mitochondria from T-4-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 Ca2+-dependent, halothane-induced loss of transmembrane potential could participate in generating acute liver damage in hyperthyroid rats exposed to halothane in non-hypoxic conditions.
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
VAIRETTI, MARIAPIA;RICHELMI, PLINIO;BELLOMO, GIORGIO
1994-01-01
Abstract
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 (T-4) pretreatment and halothane administration on Ca2+ transport and transmembrane potential were studied in isolated rat liver mitochondria. Five-day T-4-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 T-4-pretreated rats than in euthyroid animals. When mitochondria from T-4-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 Ca2+-dependent, halothane-induced loss of transmembrane potential could participate in generating acute liver damage in hyperthyroid rats exposed to halothane in non-hypoxic conditions.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
