It is well known that carbon tetrachloride and chloroform, (halogenated hydrocarbons) induce liver injury, clinically and experimentally. Halothane, one of halogenated hydrocarbons, and the most frequently used volatile anesthetic drug, has been reported in mony countries (including Japan) to induce fatal liver injuries sometime clnically. Since reported a first lethal case due to hepatic injury by halothane anesthesia, the clinical study has been progressed. In the experimental pathological fields, there are still several difficulties to overcome including such as reproducibility and the histopathological resemblance to the human cases.
In this report, the latter two points were investigated as follows : halothane was mixed with olive oil and administered of female rats, 200-260g to body weight, via two routes for oral (p. o.) and subcutaneous (s. c.) administration, rather than inhalation, for periods of 6, 8, 12 and 15 consecusecutive days. After sacrifice, histological examinations and serum chemistry analysis were conducted. Macroscopically, the livers of the 12 and 15 day groups were slightly pale and swollen. Micoscopically, clear cytoplasms were observed, partly in the 8 and 12 day group showed atrophy of the liver and the degeneration, disappearance of hepatocytes, in the central zone of the liver.
In the 15 day group, the hepatocytes degenerated and disappeared in the central zone of the liver and eosinophilic body-like degenerated hepatocytes, small hemorrhage and the infiltration of lymphocytes and plasma cells were observed. These histological pattern in the 15 day group rats are quite similar to that of human cases.
As for the other findings, fatty degeneration and slight mitosis were observed and fatty infiltrations spread from the control zone to the mid zone in the course of time.
Serum GOT activity of the 8 and 15 day groups increased significantly in comparison with control. In previous reports the main change was the fatty degeneration but only slight transient hepatocyte-degeneration was observed. In those papers, the reproducibility remains qustionable.
The reproducibility of our finding was confirmed by another experiment which was conducted six months after the first experiment and the almost same histological pattern was observed in rats.
It is considered that the liver swelling in rats, in contrast to human liver atrophy, was due to adaptive reaction by still healthy rats.
The reasons for the choice of p.o. and s.c. routes for halothane are : 1. quantitative and quick administration, 2. neither p.o. or s.c. alone could induce liver injury in rats, 3. to avoid inhalation of halothane by researchers.
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