Metabolism of the arylamide herbicide propanil. II. Effects of propanil and its derivatives on hepatic microsomal drug-metabolizing enzymes in the rat

David C McMillan, Julian E.A. Leakey, Michael P. Arlotto, JoEllyn M McMillan, Jack A. Hinson

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Propanil (3,4-dichloropropionanilide) is an arylamide herbicide that has been reported to be contaminated with the cytochrome P450 enzyme inducers 3,3′,4,4′-tetrachloroazobenzene (TCAB) and 3,3′,4,4′-tetrachloroazoxybenzene (TCAOB), which are structural analogs of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We determined if treatment of rats with TCAB, TCAOB, propanil, 3,4-dichloroaniline, TCDD, or phenobarbital induced the hepatic microsomal metabolism of propanil and 3,4-dichloroaniline. Acylamidase-catalyzed hydrolysis of propanil to 3,4-dichloroaniline was not induced by any of the pretreatments; however, hydroxylation of propanil at the 2′-position was induced by TCDD, TCAB, TCAOB, propanil, and 3,4-dichloroaniline pretreatments. Ring-and N-hydroxylations of 3,4-dichloroaniline were induced by TCDD, TCAB, TCAOB, and 3,4-dichloroaniline pretreatments. Microsomal 7-ethoxyresorufin-O-deethylase (EROD) and 7-benzoxyresorufin-O-dealkylase (BROD) activities and electrophoretic mobility of microsomal proteins suggested that cytochromes P450c and P450d were induced by TCAB and TCAOB pretreatment. EROD, BROD, and 7-pentoxyresorufin-O-dealkylase activities were slightly increased in microsomes from propanil- and 3,4-dichloroaniline-pretreated rats, which suggests that these compounds may be weak inducers of cytochrome P450 isozymes.

Original languageEnglish (US)
Pages (from-to)102-112
Number of pages11
JournalToxicology and Applied Pharmacology
Volume103
Issue number1
DOIs
StatePublished - Mar 15 1990

Fingerprint

Propanil
Herbicides
Metabolism
Rats
Derivatives
Liver
Enzymes
Pharmaceutical Preparations
Cytochrome P-450 Enzyme System
Hydroxylation
Cytochrome P-450 CYP1A1
amidase
Cytochrome P-450 CYP2B1
Electrophoretic mobility
Cytochromes
Phenobarbital
Microsomes
3,4-dichloroaniline
Isoenzymes
Hydrolysis

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Metabolism of the arylamide herbicide propanil. II. Effects of propanil and its derivatives on hepatic microsomal drug-metabolizing enzymes in the rat. / McMillan, David C; Leakey, Julian E.A.; Arlotto, Michael P.; McMillan, JoEllyn M; Hinson, Jack A.

In: Toxicology and Applied Pharmacology, Vol. 103, No. 1, 15.03.1990, p. 102-112.

Research output: Contribution to journalArticle

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