TY - JOUR
T1 - Expression of CYP1A1 and CYP1A2 in the liver and kidney of rabbits after prolonged infusion of propofol
AU - Campos, Sónia P.
AU - de Lurdes Pinto, Maria
AU - Gomes, M. Gabriela M
AU - de Pinho, Paula Guedes
AU - Monteiro, Joaquim A.
AU - Félix, Luis M.
AU - Branco, Paula S.
AU - Ferreira, Luísa M.
AU - Antunes, Luís M.
N1 - sem pdf conforme despacho.
Foundation for Science and Technology (FCT) - PEst-OE/EQB/LA0006/2011; SFRH/BD/72360/2010
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
KW - CYP1A1
KW - CYP1A2
KW - Immunohistochemistry
KW - Propofol
KW - Propofol metabolism
KW - Rabbit anesthesia
UR - http://www.scopus.com/inward/record.url?scp=84994850593&partnerID=8YFLogxK
U2 - 10.1016/j.etp.2016.07.006
DO - 10.1016/j.etp.2016.07.006
M3 - Article
C2 - 27531257
AN - SCOPUS:84994850593
SN - 0940-2993
VL - 68
SP - 521
EP - 531
JO - Experimental and Toxicologic Pathology
JF - Experimental and Toxicologic Pathology
IS - 9
ER -