Effects of Phenobarbital Pretreatment on the Response of Rat Liver to Halothane Administration

Stenger, Richard J.; Johnson, Elizabeth A.

doi:10.3181/00379727-140-36666

Cited by 21 publications

(3 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first target of reactive halothane metabolites may be cytochrome P-450, because the reactive metabolites are formed by catalysis of this hemoprotein. In uiuo, following exposure to halothane, loss of cytochrome P-450 was observed (14,15,17,18) which was maximal in experiments performed in a hypoxic atmosphere. Loss of cytochrome P-450 and binding of halothane metabolites to microsomal proteins (16,17,45,47,48,50) are of the same magnitude.…”

Section: Hypoxiamentioning

confidence: 92%

Halothane Hepatotoxicity: Relation Between Metabolic Activation, Hypoxia, Covalent Binding, Lipid Peroxidation and Liver Cell Damage

Groot

Noll

1983

Hepatology

View full text Add to dashboard Cite

Section: Hypoxiamentioning

confidence: 92%

Halothane Hepatotoxicity: Relation Between Metabolic Activation, Hypoxia, Covalent Binding, Lipid Peroxidation and Liver Cell Damage

Groot

Noll

1983

Hepatology

View full text Add to dashboard Cite

“…The important advance was the use of animals pretreated with an enzyme-inducing agent. Stenger and Johnson (1972) and Reynolds and Moslen (1974) observed sub-capsular hepatic necrosis following the administration of halothane to rats pretreated with phenobarbitone. More recently, pretreatment of rats with the polychlorinated biphenyl Aroclor 1254, was found to lead to a widespread hepatic necrosis following a halothane anaesthetic (Reynolds, Moslen and Szalo, 1976;Sipes and Brown, 1976).…”

mentioning

confidence: 98%

Toxicity of Inhalation Anaesthetic Agents

Cohen

1978

British Journal of Anaesthesia

View full text Add to dashboard Cite

Although hundreds of compounds on the chemist's shelf are known to produce anaesthesia, relatively few are used clinically. The requirements for a clinically useful anaesthetic agent are necessarily stringent and include: a wide margin of safety, total reversibility of anaesthetic effect and an absence of long-term toxicity. In addition, a successful inhalation anaesthetic agent must combine the capacity for depression of the central nervous system with low levels of interference with respiration and the circulation. The central nervous system effects must be quickly reversible. The acute depressant effects produced by the inhalation anaesthetics contrast with the slower development of long-term toxicity involving organs such as the liver, the kidneys or the reproductive system. Although such long-term toxicity associated with anaesthetics has been recognized for many years, in the past it has been considered to occur infrequently, to be of little importance and of undetermined aetiology. More recent findings suggest that not only are these long-term effects serious, but they occur more frequently than was previously recognized. In addition the aetiological factors are now beginning to be understood. RELATIONSHIP BETWEEN ANAESTHETIC METABOLISM AND TOXICITY Several reports now suggest there is a significant association between the metabolism of anaesthetic agents and the development of toxicity. Whilst the majority of drugs are metabolized in the body to less toxic derivatives, this is not always so. Occasionally, chemically inert compounds can be transformed into reactive metabolites which can combine with tissue macromolecules. These combinations may be toxic.

show abstract

“…In experimental animals, although halothane administration has produced various hepatic, structural and functional abnormalities (6)(7)(8)(9)(10)(11)(12), massive necrosis of the liver has not been reported. Recently, however, after pretreatment of rats with phenobarbital, exposure to halothane was found to cause multifocal liver necrosis, as well as hepatic functional changes ( 13 ) .…”

mentioning

confidence: 99%