Differential effects of isoflurane and halothane on the induction of heat shock proteins

Yamasaki, A Takahashi, T Suzuki, T Fujiwara, T Hirakawa, M Ohmori, E Akagi, R

A. Yamasaki et al., Differential effects of isoflurane and halothane on the induction of heat shock proteins, BIOCH PHARM, 62(3), 2001, pp. 375-382

26

INGLESE

Article

Pharmacology & Toxicology

BIOCHEMICAL PHARMACOLOGY

0006-2952 → ACNP

62

3

2001

375 - 382

ISI

0006-2952(20010801)62:3<375:DEOIAH>2.0.ZU;2-X

Isoflurane is considered to be a less hepatotoxic volatile anesthetic than halothane since it not only undergoes quantitatively much less metabolism t o form toxic reactive intermediates, but also preserves better hepatic bloo d flow. However, the biochemical basis for the reduced hepatotoxicity has n ot been elucidated. In this study, we examined the induction of two heat sh ock proteins, heat shock protein 70 (HSP70) and heme oxygenase-1 (HO-1), in the livers of rats pretreated with or without phenobarbital, followed by e xposure to isoflurane or halothane under hypoxic conditions. In the phenoba rbital-pretreated rats, the maximal induction of HSP70 was observed by halo thane-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 dys function, 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 prote in expression in the liver. In non-pretreated rats, neither isoflurane-hypo xia exposure nor halothane-hypoxia exposure caused apparent hepatic injury. There was also no induction of HSP70 or HO-1 mRNA by these treatments in n on-pretreated animals. These findings demonstrate that there is a significa nt difference in hepatic injury, and in the induction of HO-1 and HSP70 bet ween halothane-hypoxia and isoflurane-hypoxia treatments. Isoflurane is kno wn 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 asses sed by reduced induction of heat shock proteins compared with halothane tre atment. (C) 2001 Elsevier Science Inc. All rights reserved.