Metabolism and Cytotoxicity of Hydrazine in Isolated Rat Hepatocytes1’

Atsuko Noda, Toshiaki Sendo, Kohji Ohno, Shigeru Goto, Hiroshi Noda

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The relationship between the metabolism and hepatotoxicity of hydrazine (Hz) was studied in an isolated rat hepatocyte system. After incubation at 37 °C for 60 min; the concentration of Hz decreased to 34% of the initial value-(from 98 to 33 nmol/ml). A further pronounced loss was observed when Hz was incubated with hepatocytes isolated from rats which had been pretreated with phenobarbital (PB) or rifampicin. Since metyrapone and piperonylbutoxide inhibited the metabolism in the systems obtained from both PB-pretreated rats and untreated rats, an important role of hepatic cytochrome P-450 in Hz oxidation was suggested. The difference spectrum of Hz with cytochrome P-450 in isolated rat hepatocytes demonstrated the formation of complexes between metabolic intermediates of Hz and cytochrome P-450. The trypan blue exclusion test, the measurement of K,+ level and the determination of glutathione content retained in the cells were also performed. The results suggested that Hz is cytotoxic to isolated rat hepatocytes.

Original languageEnglish
Pages (from-to)2538-2544
Number of pages7
JournalChemical and Pharmaceutical Bulletin
Volume35
Issue number6
DOIs
Publication statusPublished - Jan 1 1987
Externally publishedYes

Keywords

  • cytotoxicity
  • hepatocytes
  • hydrazine
  • metabolism
  • rat

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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