Chronotoxicity of bromobenzene-induced hepatic injury in mice

Hiroki Yoshioka, Tsunemasa Nonogaki, Nobuyuki Fukuishi, Yasuro Shinohara, Gi Wook Hwang, Katsumi Ohtani, Nobuhiko Miura

研究成果: Article

15 引用 (Scopus)


The aim of the present study is to investigate whether or not bromobenzene (BB) toxicity varies with circadian periodicity. Seven-week-old male ICR mice were injected with 900 mg/kg (5.73 mmol/kg) BB intraperitoneally at 4 different time points of a day (zeitgeber time [ZT]: ZT0, ZT6, ZT12, and ZT18). Mortality was then monitored for 7 days after injection. Interestingly, mice were sensitive to BB acute toxicity at ZT6 while tolerant at ZT18. Moreover, in mice that were given a non-le-thal dose of BB (540 mg (3.44 mmol)/kg), levels of alanine aminotransferase and aspartate aminotransferase, used as markers of hepatic injury, markedly increased in response to injection at ZT6, but did not increase significantly in response to injection at ZT18. In contrast, the markers of renal injury (creatinine and blood urea nitrogen), showed no significant difference in response to the two injection times. To further investigate this extreme circadian variation, we examined hepatic and renal lipid peroxidation levels, and conducted histopathological studies. Similar to our observation with alanine aminotransferase and creatinine, hepatic lipid peroxidation and histopathological changes were more pronounced than renal changes, and showed circadian variation. Our present investigation demonstrated that BB-induced mortality had clear circadian variation, and suggested that hepatic injury was one of the important factors for determination of this variation.

ジャーナルJournal of Toxicological Sciences
出版物ステータスPublished - 2017 1 1

ASJC Scopus subject areas

  • Toxicology

フィンガープリント Chronotoxicity of bromobenzene-induced hepatic injury in mice' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    Yoshioka, H., Nonogaki, T., Fukuishi, N., Shinohara, Y., Hwang, G. W., Ohtani, K., & Miura, N. (2017). Chronotoxicity of bromobenzene-induced hepatic injury in mice. Journal of Toxicological Sciences, 42(2), 251-258.