Expression of CYP1A1 and CYP1A2 in the liver and kidney of rabbits after prolonged infusion of propofol

Sónia P. Campos, Maria de Lurdes Pinto, M. Gabriela M Gomes, Paula Guedes de Pinho, Joaquim A. Monteiro, Luis M. Félix, Paula S. Branco, Luísa M. Ferreira, Luís M. Antunes

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Abstract

Background Propofol biotransformation occurs in the liver via hydroxylation by CYP450 enzymatic complex and by glucuronidation, however extra-hepatic metabolism has also been described. Objectives To better understand the metabolic pathways involved in propofol biotransformation, the expression of CYP1A1, CYP1A2, the enzymatic and non-enzymatic antioxidant activity and the amount of propofol and its non-conjugated metabolites were investigated. Methods Twenty-one NewZealand rabbits were allocated into three groups continuously treated for 20 h. Each group received: NaCl 0.9%, vehicle (SMOFlipid) and propofol 2% (Lipuro). At the end, liver and kidney samples were collected for histopathology and immunohistochemistry and plasma for quantification of propofol and its metabolites. Results CYP1A1 and CYP1A2 were observed in zone 1 and zone 3 regions of the liver acinus. The propofol and saline groups showed a higher expression of CYP1A1 when compared to vehicle group. Propofol significantly increased CYP1A2 expression, compared to saline. CYP1A1 and CYP1A2 immunoexpression were observed in the kidney but no differences were registered between groups. Conclusions This suggests that propofol may act as selective inhibitor of CYP1A1 and an inducer of CYP1A2 expression in different regions of the liver. Propofol seems to have an antioxidative protective effect on liver parenchyma, comparatively to the emulsion alone. In the rabbit, extra-hepatic propofol biotransformation may also occur in the kidney.

Original languageEnglish
Pages (from-to)521-531
Number of pages11
JournalExperimental and Toxicologic Pathology
Volume68
Issue number9
DOIs
Publication statusPublished - 1 Oct 2016

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Keywords

  • CYP1A1
  • CYP1A2
  • Immunohistochemistry
  • Propofol
  • Propofol metabolism
  • Rabbit anesthesia

Cite this

Campos, S. P., de Lurdes Pinto, M., Gomes, M. G. M., de Pinho, P. G., Monteiro, J. A., Félix, L. M., ... Antunes, L. M. (2016). Expression of CYP1A1 and CYP1A2 in the liver and kidney of rabbits after prolonged infusion of propofol. Experimental and Toxicologic Pathology, 68(9), 521-531. https://doi.org/10.1016/j.etp.2016.07.006