Effect of phenobarbital on hepatic eicosanoid concentrations in rats

Rhonda S. Peebles, Howard P. Glauert

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5 Scopus citations


Phenobarbital is an efficacious tumor-promoting agent in the liver. Studies using inhibitors of eicosanoid synthesis have suggested that eicosanoids are important in the promotion of hepatocarcinogenesis by phenobarbital. We therefore hypothesized that hepatic eicosanoid concentrations are altered following phenobarbital administration. Male Sprague-Dawley rats were fed one of four levels of phenobarbital (0, 0.02, 0.05, and 0.1%). Eight rats from each of the four groups were killed after 10, 24, and 44 days for determination of liver weight and for preparation of microsomes. No significant difference was found among rat weights; however, liver weights were significantly higher in rats fed phenobarbital. Assay of benzyloxyresorufin-O-dealkylase activity showed that cytochromes P-450 2B1 and 2B2 were induced in response to phenobarbital administration. Prostaglandin E2 concentrations were found to be significantly decreased by phenobarbital treatment after 10 and 24 days, but not after 44 days. Prostaglandin F(2α) levels were decreased only by the lowest dietary phenobarbital concentration. Hepatic concentrations of leukotriene C4 were decreased significantly at 10 days and at 44 days (only for the group administered the highest percentage concentration of phenobarbital), but not at 24 days. These results show that the investigated eicosanoids are generally slightly decreased by phenobarbital administration. Elevated eicosanoid levels therefore do not appear to be necessary for the promoting activity of phenobarbital.

Original languageEnglish
Pages (from-to)646-650
Number of pages5
JournalArchives of Toxicology
Issue number10
StatePublished - 1997

Bibliographical note

Funding Information:
Acknowledgements We thank Dr Larry Robertson and Parveneh Espandiari for their help with the resorufin assays. This research was supported by a research supplement for under-represented minorities from the National Institute for Environmental Health Sciences (ES05815), by a grant from the National Cancer Institute (CA01688), and by the Kentucky Agricultural Experiment Station.


  • Hepatocarcinogenesis
  • Leukotriene
  • Phenobarbital
  • Prostaglandin

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis


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