Differential effects of isoflurane and halothane on the induction of heat shock proteins.
Isoflurane is considered to be a less hepatotoxic volatile anesthetic than halothane since it not only undergoes quantitatively much less metabolism to form toxic reactive intermediates, but also preserves better hepatic blood flow. However, the biochemical basis for the reduced hepatotoxicity has not been elucidated. In this study, we examined the induction of two heat shock proteins, heat shock protein 70 (HSP70) and heme oxygenase-1 (HO-1), in the livers of rats pretreated with or without phenobarbital, followed by exposure to isoflurane or halothane under hypoxic conditions. In the phenobarbital-pretreated rats, the maximal induction of HSP70 was observed by halothane-hypoxia treatment, followed by a half-maximal induction by isoflurane-hypoxia treatment, and less than 30% induction by hypoxia treatment alone. Serum alanine aminotransferase (ALT) activity, an indicator of hepatic dysfunction, which correlated well with the extent of centrilobular necrosis, showed similar changes with increases in HSP70 mRNA. In contrast, HO-1 mRNA was induced only by treatment with halothane-hypoxia. In addition, changes in the expression of HSP70 and HO-1 mRNAs were correlated with their protein expression in the liver. In non-pretreated rats, neither isoflurane-hypoxia exposure nor halothane-hypoxia exposure caused apparent hepatic injury. There was also no induction of HSP70 or HO-1 mRNA by these treatments in non-pretreated animals. These findings demonstrate that there is a significant difference in hepatic injury, and in the induction of HO-1 and HSP70 between halothane-hypoxia and isoflurane-hypoxia treatments. Isoflurane is known to be safer than halothane, which may, in part, be accounted for by the generation of less oxidative stress in the presence of isoflurane, as assessed by reduced induction of heat shock proteins compared with halothane treatment.
Yamasaki
A
A
Department of Anesthesiology and Resuscitology, Okayama University Medical School, 2-5-1 Shikata-cho, 700-8558, Okayama-shi, Japan.
Takahashi
T
T
Suzuki
T
T
Fujiwara
T
T
Hirakawa
M
M
Ohmori
E
E
Akagi
R
R
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D015687:Cell Hypoxia; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1; D007530:Isoflurane / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018685:Anesthetics, Inhalation; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D007530:Isoflurane; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D010100:Oxygen; D006221:Halothane