It is well known that halothane was introduced for clinical use as an anesthetic agent in 1956 and has since enjoyed enormous and ever increasing popularity because, of its pharmacological properties and its safety as a non explosive agent.
Numerous investigators reported that varying degree of hepatic injury have been noted after halothane anesthesia in clinical experiences. Although many investigators failed to demonstrate that no hepatic damage is caused by halothane in experimental animals, careful consideration had been given to the possibility that halothane, in common with many other halogenated hydrocarbon, might damage the liver, and potential hepatotoxicity caused by halothane has not been definitely established.
It is important to note that the metabolism of volatile anesthetic agent occurs in microsomes where most of the drug metabolizing enzymes are known to be present. Halothane is metabolized, in part, by the microsomal drug metabolizing enzyme systems of the liver, and induction of drug metabolizing enzyme systems increases this metabolise.
While pretreatment of phenobarbital, a well known enzyme inducer has already been shown to enhance the hepatotoxicity of another halogenated hydrocarbons. Since the metabolites of halothane may be toxic, it has been suggested that hepatic drug metabolizing enzyme induction might be expected to potentiate the hepatotoxicity.
The present investigation, therefore, has demonstrated whether much drug metabolizing enzyme induction would affect the response of liver to halothane with phenobarbital pretreatment by repeat administration.
A total of 105 healthy male albino mice divided into the control, the phenobarbital treated, the halothane treated, and the phenobarbital halothane treated groups, and each group of the experimental animals. were divided into the first, the second, and the third day groups according to repeat administration of phenobarbital or and halothane.
The experimental animals were given 50 mg per kg of body weight of phenobarbital twice a day with an interval of 6 hours after having been deprived of food except drinking water ad libitum, and 0.5 ml per. kg of body weight of halothane in olive oil are injected intraperitoneally with 6 hours interval after the administration of phenobarbital. The animals were killed at 12 hours after the last administration of halothane.
The specimens, which were obtained from the left. anterior lobe of the liver, were stained with methyl green-pyronin and oil red 0 methods and observed with light microscope, and the specimens were also stained with uranyl acetate and lead citrate double contrast methods and observed with Hitachi H-300 model electron microscope.
The liver of the phenobarbital-halothane treated mice showed as followingg significant changes;
1. the pyroninophilic granules were reduced markedly in the hepatic parenchymal cells of the centrilobular and intermediate zones by repeated administration of phenobarbital and halothane.
2. the fat deposits were observed markedly in the hepatic parenchymal cells of the centrilobular and intermediate zones by repeated administration of phenobarbital and halothane.
3. a prominent dilatation, sacculation of the cisternae of RER in companied with dissociation of membrane bounded ribosomes, disaggregation of free polysomes, proliferation of SER associated with depletion of glycogen particles, atrophies of cisternae of Golgi complex, and production of numerous lipid droplets were recognized in the hepatic parenchymal cells by repeated administration of phenobarbital and halothane.
Consequently it is suggested that hepatic damage was induced with repeated administration of phenobarbital and halothane in mice.
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