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Respective roles of hypoxia and halothane metabolism in halothane‐induced liver injury in rats
Author(s) -
Hatano Hitoshi,
Nomura Fumio,
Ohnishi Kunihiko,
Iijima Toshihiko,
Hayasaka Akira,
Iida Shinji,
Koen Hirofumi,
Okuda Kunio
Publication year - 1985
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840050214
Subject(s) - halothane , hypoxia (environmental) , phenobarbital , endocrinology , metabolism , medicine , enflurane , anesthesia , centrilobular necrosis , liver injury , chemistry , oxygen , organic chemistry
To evaluate the respective roles of halothane metabolism and hypoxia in rats with halothane hepatotoxicity, experiments were designed with special reference to blood gas. After pretreatment with phenobarbital (80 mg per kg., i.p.) for four consecutive days, rats were exposed to 1.0% halothane under a mildly hypoxic condition (FiO 2 = 14%) for 2 hr. Since halothane anesthesia caused significant decrease in PaO 2 levels, rats exposed to a highly hypoxic atmosphere (FiO 2 = 10%) in which PaO 2 levels were comparable to those in the halothane group, served as the control. In the halothane group, marked centrilobular necrosis and elevation of SGPT activity were observed; neither significant histological lesions nor elevation of transaminase activity occurred in the highly hypoxic group. Although phenobarbital treatment did not decrease PaO 2 levels during halothane anesthesia, the serum fluoride level, which appears to reflect quantitatively the reductive pathway of halothane metabolism, increased. These results strongly indicate that halothane metabolism rather than hypoxia, per se , plays a major role in development of halothane‐induced liver injury in rats.