title: Expression of CYP1A1 and CYP1A2 in the liver and kidney of rabbits after prolonged infusion of propofol.
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.
  
  
  OBJECTIVE
  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 20h. 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.
authors.affiliation: Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB) and Veterinary Sciences Department from the School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5001-801, Vila Real, Portugal; Institute for Research and Innovation in Health (i3S), Laboratory Animal Science, Institute of Molecular and Cell Biology (IBMC), University of Porto, Rua Alfredo Allen, nº 208, 4200-135 Porto, Portugal; UCIBIO@REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Portugal. Electronic address: soniapatcampos@gmail.com.
authors.forename: Sónia P
authors.initials: SP
authors.lastname: Campos
authors.affiliation: Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB) and Veterinary Sciences Department from the School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5001-801, Vila Real, Portugal.
authors.forename: Maria
authors.initials: M
authors.lastname: de Lurdes Pinto
authors.affiliation: Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB) and Veterinary Sciences Department from the School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5001-801, Vila Real, Portugal.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Gomes
authors.affiliation: UCIBIO@REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Portugal.
authors.forename: Paula Guedes
authors.initials: PG
authors.lastname: de Pinho
authors.affiliation: IINFACTS - Instituto de Investigação e Formação Avançada em Ciências e Tecnologia da Saúde, CESPU, Paredes, Portugal and Faculty of Medicine, University of Porto, Portugal.
authors.forename: Joaquim A
authors.initials: JA
authors.lastname: Monteiro
authors.affiliation: Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB) and Veterinary Sciences Department from the School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5001-801, Vila Real, Portugal.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Félix
authors.affiliation: LAQV, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516, Portugal.
authors.forename: Paula S
authors.initials: PS
authors.lastname: Branco
authors.affiliation: LAQV, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516, Portugal.
authors.forename: Luísa M
authors.initials: LM
authors.lastname: Ferreira
authors.affiliation: Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB) and Veterinary Sciences Department from the School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5001-801, Vila Real, Portugal; Institute for Research and Innovation in Health (i3S), Laboratory Animal Science, Institute of Molecular and Cell Biology (IBMC), University of Porto, Rua Alfredo Allen, nº 208, 4200-135 Porto, Portugal.
authors.forename: Luís M
authors.initials: LM
authors.lastname: Antunes
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D006993:Hypnotics and Sedatives / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D015742:Propofol / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits
chemical_list: D006993:Hypnotics and Sedatives; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D015742:Propofol
keywords: CYP1A1; CYP1A2; Immunohistochemistry; Propofol; Propofol metabolism; Rabbit anesthesia