Hapten carrier conjugates associated with halothane hepatitis.
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Animals↗
Biomedical subjects
L E Butler
Publications and source records attributed to L E Butler.
Sensitivity of selected drug biotransformation enzymes to dietary protein levels in adult F344 male rats.
Adult male Fischer 344 rats were fed inadequate, adequate, and excessive quantities of dietary protein (8, 12, and 22%, respectively) for a period of 14 days. An increase in dietary protein did not increase liver weight but resulted in an increase in cytochrome P-450 content and 7-ethoxycoumarin O-deethylase activity. No significant difference in glutathione S-transferase activity was observed at the three protein levels. The in vivo hepatotoxicity of bromobenzene increased with an elevation in dietary protein intake from 12 to 22%. These data from mature rats follow trends similar to findings we have reported previously with juvenile rats.
Animals↗
The effect of dietary protein levels on xenobiotic biotransformations in F344 male rats.
Diets containing protein levels of 8, 12, and 22% were fed for 14 days to Fischer 344 male weanling rats. Enzyme activities in liver and kidney were measured using several substrates for each of the following enzyme systems: Cytochrome P-450-dependent monooxygenase, ester hydrolysis, and conjugations with sulfate, glutathione, and glucuronic acid. Enzyme activities, for the various mechanisms, decreased from 15 to 65% with decreased dietary protein, with the exception of glucuronide and sulfate conjugation, which increased with decreased dietary protein. In vivo effects were evaluated by measuring hexobarbital sleeping time, procaine paralysis time, and bromobenzene hepatotoxicity. Increased dietary protein shortened hexobarbital sleeping time and procaine paralysis time, and increased procaine lethality, whereas low protein intake protected against bromobenzene hepatotoxicity. These data suggest that typical laboratory diets (22-25% protein) may provide artificially altered activities of xenobiotic biotransformation in rats, relative to nutritionally adequate (12% protein) diets.
Animals↗
The calcium-binding protein calreticulin is covalently modified in rat liver by a reactive metabolite of the inhalation anesthetic halothane.
A general procedure is presented for the isolation of several liver microsomal target proteins of the reactive trifluoroacetyl halide metabolite of halothane. It was found that most of these proteins could be selectively extracted from microsomes with 0.1% sodium deoxycholate and separated into partially purified fractions by DEAE-Sepharose anion-exchange chromatography. Using this method, we describe the isolation and identification of a 63-kDa target protein of halothane in rat liver. Amino acid sequences of the N-terminal and of several internal peptides of the protein, as well as the deduced amino acid sequence of a nearly full-length rat liver cDNA clone of the protein, showed 98% identity with a reported murine cDNA that encodes for calreticulin, a major calcium-binding protein of the lumen of endoplasmic reticulum. Although it remains to be determined what role calreticulin has in the development of halothane hepatitis, this study has shown that calreticulin can be a target of reactive metabolites of xenobiotics.
Amino Acid Sequence↗