Suppression of microsomal cytochrome P450-dependent monooxygenases and mitochondrial oxidative phosphorylation by fullerenol, a polyhydroxylated fullerene C60

Tzuu Huei Ueng, Jaw Jou Kang, Hui Wu Wang, Yu Wen Cheng, Long Y. Chiang

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

The acute toxicity of fullerenol-1 was determined using mice pretreated intraperitoneally (i.p.) with polyhydroxylated C60 derivatives. The LD50 value of fullerenol-1 was estimated to be 1.2 g/kg. Pretreatments with 0.5 and 1.0 g/kg fullerenol-1 decreased cytochromes P450 and b5 contents, and NADPH-cytochrome P450 reductase, benzo[a]pyrene hydroxylase, 7-ethoxycoumarin O-deethylase, aniline hydroxylase, and erythromycin N-demethylase activities in liver microsomes. Pretreatments with 0.01 and 0.1 g/kg fullerenol-1 had no effect on these monooxygenases. Additions of fullerenol-1 to mouse liver microsomes suppressed monooxygenases activities toward benzo[a]pyrene, 7-ethoxycoumarin, aniline, and erythromycin with IC50 values of 42, 94, 102 and 349 μM, respectively. Fullerenol-1 exhibited noncompetitive and mixed-type of inhibition in benzo[a]pyrene hydroxylation and 7-ethoxycoumarin O-deethylation, respectively. Additions of fullerenol-1 to rat liver mitochondria resulted in a dose-dependent inhibition of ADP-induced uncoupling and markedly inhibited mitochondrial Mg2+-ATPase activity with an IC50 value of 7.1 μM. These results demonstrate that fullerenol-1 can suppress the levels of the microsomal enzymes in vivo and decrease the activities of P450-dependent monooxygenase and mitochondrial oxidative phosphorylation in vitro.

Original languageEnglish
Pages (from-to)29-37
Number of pages9
JournalToxicology Letters
Volume93
Issue number1
DOIs
Publication statusPublished - Sep 19 1997
Externally publishedYes

Keywords

  • Fullerene
  • Mitochondrial dysfunction
  • P450 suppression

ASJC Scopus subject areas

  • Toxicology

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