Microsomal azoreduction and glucuronidation in the metabolism of dimethylaminoazobenzene by the rat liver

H. Raza, W. G. Levine, N. Roy Chowdhury, Jayanta Roy-Chowdhury

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

1. Enzymic azoreduction of the hepatocarcinogen, N, N- dimethyl-4-aminoazobenzene (DAB) and glucuronidation of its ring-hydroxylation product, 4'hydroxy-DAB, by hepatic microsomal fractions in vitro were studied during an eight day period of hepatic regeneration following partial hepatectomy in Wistar rats. Azoreduction of DAB and its N-demethylated metabolites did not significantly change during hepatic regeneration in contrast to N-demethylation of these dyes which is profoundly suppressed during regeneration. UDP-Glucuronosyltransferase (UDP-GT) activity towards 4'hydroxy-DAB was partially depressed during the regeneration period, but the depression was considerably less than that for bilirubin. Transferase activity towards 4-nitrophenol, after initial depression, returned to normal levels after the third day of partial hepatectomy. 2. In Gunn rats, microsomal UDP-GT activity towards bilirubin was undetectable, whereas transferase activity toward 4-nitrophenol was 50% of normal. Addition of diethylnitrosamine (DEN) in vitro restored transferase activity towards 4-nitrophenol to normal levels, but the activity towards bilirubin was unaffected. Gunn rat UDP-GT activity towards 4'hydroxy-DAB was 25% of normal and was partially activated upon addition of DEN in vitro. 3. Treatment with clofibrate of naphthoflavone induced hepatic microsomal bilirubin- and 4-nitrophenol-specific UDP-GT activities, respectively; both agents induced transferase activity towards 4'hydroxy-DAB. Triiodothyronine, which induces 4'nitrophenol-specific UDP-GT and depresses bilirubin-specific UDPG, had little effect on 4'hydroxy-DAB UDP-GT activity. 4. The results indicate that microsomal reductive metabolism of DAB is affected differently from that of its oxidative metabolism during liver regeneration. Glucuronidation of 4'hydroxy-DAB appears to be catalysed by both bilirubin- and 4-nitrophenolspecific UDP-GT isoforms which are differentially expressed during liver regeneration.

Original languageEnglish (US)
Pages (from-to)669-677
Number of pages9
JournalXenobiotica
Volume17
Issue number6
DOIs
StatePublished - 1987

Fingerprint

p-Dimethylaminoazobenzene
Glucuronosyltransferase
Metabolism
Liver
Rats
Bilirubin
Transferases
Regeneration
Gunn Rats
Diethylnitrosamine
bilirubin glucuronoside glucuronosyltransferase
Liver Regeneration
Hepatectomy
Uridine Diphosphate Glucose
Clofibrate
Hydroxylation
Triiodothyronine
Metabolites
Protein Isoforms
Coloring Agents

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Biochemistry
  • Health, Toxicology and Mutagenesis
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Microsomal azoreduction and glucuronidation in the metabolism of dimethylaminoazobenzene by the rat liver. / Raza, H.; Levine, W. G.; Chowdhury, N. Roy; Roy-Chowdhury, Jayanta.

In: Xenobiotica, Vol. 17, No. 6, 1987, p. 669-677.

Research output: Contribution to journalArticle

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abstract = "1. Enzymic azoreduction of the hepatocarcinogen, N, N- dimethyl-4-aminoazobenzene (DAB) and glucuronidation of its ring-hydroxylation product, 4'hydroxy-DAB, by hepatic microsomal fractions in vitro were studied during an eight day period of hepatic regeneration following partial hepatectomy in Wistar rats. Azoreduction of DAB and its N-demethylated metabolites did not significantly change during hepatic regeneration in contrast to N-demethylation of these dyes which is profoundly suppressed during regeneration. UDP-Glucuronosyltransferase (UDP-GT) activity towards 4'hydroxy-DAB was partially depressed during the regeneration period, but the depression was considerably less than that for bilirubin. Transferase activity towards 4-nitrophenol, after initial depression, returned to normal levels after the third day of partial hepatectomy. 2. In Gunn rats, microsomal UDP-GT activity towards bilirubin was undetectable, whereas transferase activity toward 4-nitrophenol was 50{\%} of normal. Addition of diethylnitrosamine (DEN) in vitro restored transferase activity towards 4-nitrophenol to normal levels, but the activity towards bilirubin was unaffected. Gunn rat UDP-GT activity towards 4'hydroxy-DAB was 25{\%} of normal and was partially activated upon addition of DEN in vitro. 3. Treatment with clofibrate of naphthoflavone induced hepatic microsomal bilirubin- and 4-nitrophenol-specific UDP-GT activities, respectively; both agents induced transferase activity towards 4'hydroxy-DAB. Triiodothyronine, which induces 4'nitrophenol-specific UDP-GT and depresses bilirubin-specific UDPG, had little effect on 4'hydroxy-DAB UDP-GT activity. 4. The results indicate that microsomal reductive metabolism of DAB is affected differently from that of its oxidative metabolism during liver regeneration. Glucuronidation of 4'hydroxy-DAB appears to be catalysed by both bilirubin- and 4-nitrophenolspecific UDP-GT isoforms which are differentially expressed during liver regeneration.",
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N2 - 1. Enzymic azoreduction of the hepatocarcinogen, N, N- dimethyl-4-aminoazobenzene (DAB) and glucuronidation of its ring-hydroxylation product, 4'hydroxy-DAB, by hepatic microsomal fractions in vitro were studied during an eight day period of hepatic regeneration following partial hepatectomy in Wistar rats. Azoreduction of DAB and its N-demethylated metabolites did not significantly change during hepatic regeneration in contrast to N-demethylation of these dyes which is profoundly suppressed during regeneration. UDP-Glucuronosyltransferase (UDP-GT) activity towards 4'hydroxy-DAB was partially depressed during the regeneration period, but the depression was considerably less than that for bilirubin. Transferase activity towards 4-nitrophenol, after initial depression, returned to normal levels after the third day of partial hepatectomy. 2. In Gunn rats, microsomal UDP-GT activity towards bilirubin was undetectable, whereas transferase activity toward 4-nitrophenol was 50% of normal. Addition of diethylnitrosamine (DEN) in vitro restored transferase activity towards 4-nitrophenol to normal levels, but the activity towards bilirubin was unaffected. Gunn rat UDP-GT activity towards 4'hydroxy-DAB was 25% of normal and was partially activated upon addition of DEN in vitro. 3. Treatment with clofibrate of naphthoflavone induced hepatic microsomal bilirubin- and 4-nitrophenol-specific UDP-GT activities, respectively; both agents induced transferase activity towards 4'hydroxy-DAB. Triiodothyronine, which induces 4'nitrophenol-specific UDP-GT and depresses bilirubin-specific UDPG, had little effect on 4'hydroxy-DAB UDP-GT activity. 4. The results indicate that microsomal reductive metabolism of DAB is affected differently from that of its oxidative metabolism during liver regeneration. Glucuronidation of 4'hydroxy-DAB appears to be catalysed by both bilirubin- and 4-nitrophenolspecific UDP-GT isoforms which are differentially expressed during liver regeneration.

AB - 1. Enzymic azoreduction of the hepatocarcinogen, N, N- dimethyl-4-aminoazobenzene (DAB) and glucuronidation of its ring-hydroxylation product, 4'hydroxy-DAB, by hepatic microsomal fractions in vitro were studied during an eight day period of hepatic regeneration following partial hepatectomy in Wistar rats. Azoreduction of DAB and its N-demethylated metabolites did not significantly change during hepatic regeneration in contrast to N-demethylation of these dyes which is profoundly suppressed during regeneration. UDP-Glucuronosyltransferase (UDP-GT) activity towards 4'hydroxy-DAB was partially depressed during the regeneration period, but the depression was considerably less than that for bilirubin. Transferase activity towards 4-nitrophenol, after initial depression, returned to normal levels after the third day of partial hepatectomy. 2. In Gunn rats, microsomal UDP-GT activity towards bilirubin was undetectable, whereas transferase activity toward 4-nitrophenol was 50% of normal. Addition of diethylnitrosamine (DEN) in vitro restored transferase activity towards 4-nitrophenol to normal levels, but the activity towards bilirubin was unaffected. Gunn rat UDP-GT activity towards 4'hydroxy-DAB was 25% of normal and was partially activated upon addition of DEN in vitro. 3. Treatment with clofibrate of naphthoflavone induced hepatic microsomal bilirubin- and 4-nitrophenol-specific UDP-GT activities, respectively; both agents induced transferase activity towards 4'hydroxy-DAB. Triiodothyronine, which induces 4'nitrophenol-specific UDP-GT and depresses bilirubin-specific UDPG, had little effect on 4'hydroxy-DAB UDP-GT activity. 4. The results indicate that microsomal reductive metabolism of DAB is affected differently from that of its oxidative metabolism during liver regeneration. Glucuronidation of 4'hydroxy-DAB appears to be catalysed by both bilirubin- and 4-nitrophenolspecific UDP-GT isoforms which are differentially expressed during liver regeneration.

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