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Peripheral esterases in the rat: effects of classical inducers
N W McCracken1, P G Blain, F M Williams
1Toxicology Unit, Medical School, Newcastle University, UK.
Chemico-Biological Interactions
|June 1, 1993
Summary
Phenobarbitone treatment induces liver microsomal esterases, including paraoxonase and carboxylesterase, in rats. Extrahepatic esterases in lung tissue were also induced, highlighting differential enzyme responses to chemical exposure.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Enzyme induction plays a crucial role in drug metabolism and detoxification.
- Carboxylesterases are a significant class of enzymes involved in hydrolyzing various xenobiotics.
- Understanding the differential induction of esterases by various compounds is vital for assessing their toxicological profiles.
Purpose of the Study:
- To investigate the inductive effects of phenobarbitone, beta-naphthoflavone, and clofibric acid on specific esterase activities in rat liver microsomes and extrahepatic tissues.
- To characterize the substrate specificity of induced esterases, focusing on paraoxonase, aryl esterase, and fluazifop butyl esterase (carboxylesterase).
Main Methods:
- Rats were pretreated with phenobarbitone, beta-naphthoflavone, or clofibric acid.
- Liver microsomes and lung cytosol were isolated for enzyme activity assays.
- Esterase activities (paraoxonase, aryl esterase, fluazifop butyl esterase, phenylacetate esterase) were measured spectrophotometrically.
Main Results:
- Phenobarbitone significantly induced liver microsomal paraoxonase, aryl esterase, and fluazifop butyl esterase (carboxylesterase) activities.
- Beta-naphthoflavone and clofibric acid did not induce these hepatic microsomal esterases.
- Lung cytosolic fluazifop butyl esterase and phenylacetate esterase activities were induced by phenobarbitone.
Conclusions:
- Phenobarbitone is a potent inducer of specific hepatic microsomal esterases and certain extrahepatic esterases in rats.
- The induction patterns suggest distinct regulatory mechanisms for different esterase isozymes and tissue distribution.
- These findings contribute to understanding the xenobiotic-metabolizing enzyme system and its modulation by chemical agents.