Citation

Xuan GD, Liu ZQ. Chinese Journal of Pharmacology and Toxicology 1995; 9(1): 3-7.

Copyright

(Copyright © 1995)

DOI

unavailable

PMID

unavailable

Abstract

The aerobic incubation of p-chloro-O-toluidine (PCT) with NADPH fortified hepatic microsomes of naive rats resulted in non-detectable cytochrome P450 metabolic intermediate (MI) complex formation. However, pretreatment of rats with phenobarbital (PB) or Aroclor 1254 (ARO) significantly increased the capability of hepatic microsomes to form P450 MI complex with PCT, whereas dexamethasone or β-naphthoflavone pretreatment showed no effect on MI complex formation. The correlation of PCT MI complex formation with other marker activities of P450s, e.g. ethoxyresorufin-O-deethylase, pentoxyresorufin-O-dealkylase (PROD), aminopyrine-N-demethylase, and P450 MI complex formation from 4-aminotertbutyl-benzoate or triacetyloleandomycin were examined. Among those tested markers, only PROD (the marker of cytochrome P450 II B) was significantly correlated with PCT MI complex formation with the regression line passing through the origin. Pretreatment of PB induced rats with secobarbital, a suicide inactivator of cytochrome P450 II B, diminished the rat hepatic microsomal PCT MI complex formation, PROD and P450 content in similar degree. These results revealed that PCT MI complex formation might be used as a new probe to characterize P450 II B.

Language: en

Keywords

male; article; controlled study; unclassified drug; nonhuman; enzyme activity; phenobarbital; animal experiment; dexamethasone; rat; cytochrome P450; animal tissue; secobarbital; reduced nicotinamide adenine dinucleotide phosphate; intraperitoneal drug administration; 4 amino tert butylbenzoate; 4 chloro ortho toluidine; aminopyrine n demethylase; aroclor 1254; beta naphthoflavone; complex formation; cytochrome p450 isoenzyme; ethoxyresorufin deethylase; liver microsome metabolism; metabolic detoxification, drug; metabolic intermediate complex; pentoxyresorufin dealkylase; toluidine derivative; toluidines,p-chloro-O-toluidine; troleandomycin