TY - JOUR
T1 - Comparison of three fluorescent CYP3A substrates in two vertebrate models: pig and Atlantic salmon
AU - Zlabek, Vladimir
AU - Zamaratskaia, Galia
PY - 2012
Y1 - 2012
N2 - We investigated in vitro inhibitory effects of ketoconazole (KTZ) on cytochrome P450 activity in microsomes from pigs and Atlantic salmon. The following enzymatic reactions were studied: 7-benzyloxyresorufin and 7-ethoxyresorufin O-dealkylation (BROD and EROD, respectively), 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylation (BFCOD) and 7-benzyloxyquinoline O-debenzylation (BQOD). KTZ was a potent non-competitive inhibitor of BROD and BQOD in the microsomes from pigs, whereas in the microsomes from Atlantic salmon, these reactions were competitively inhibited by KTZ. BFCOD activity was inhibited by KTZ in a non-competitive manner in both species. KTZ non-competitively inhibited EROD in Atlantic salmon, but not in porcine microsomes. The activity of BROD and BQOD was higher in male than that in female pigs, but the activity of BFCOD showed no sex-related differences.
AB - We investigated in vitro inhibitory effects of ketoconazole (KTZ) on cytochrome P450 activity in microsomes from pigs and Atlantic salmon. The following enzymatic reactions were studied: 7-benzyloxyresorufin and 7-ethoxyresorufin O-dealkylation (BROD and EROD, respectively), 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylation (BFCOD) and 7-benzyloxyquinoline O-debenzylation (BQOD). KTZ was a potent non-competitive inhibitor of BROD and BQOD in the microsomes from pigs, whereas in the microsomes from Atlantic salmon, these reactions were competitively inhibited by KTZ. BFCOD activity was inhibited by KTZ in a non-competitive manner in both species. KTZ non-competitively inhibited EROD in Atlantic salmon, but not in porcine microsomes. The activity of BROD and BQOD was higher in male than that in female pigs, but the activity of BFCOD showed no sex-related differences.
KW - ketoconazole
KW - 7-ethoxyresorufin
KW - 7-benzyloxyresorufin
KW - 7-benzyloxy-4-trifluoromethylcoumarin
KW - 7-benzyloxyquinoline
KW - ketoconazole
KW - 7-ethoxyresorufin
KW - 7-benzyloxyresorufin
KW - 7-benzyloxy-4-trifluoromethylcoumarin
KW - 7-benzyloxyquinoline
UR - https://res.slu.se/id/publ/42472
UR - http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8498703
U2 - 10.1017/S1751731111002096
DO - 10.1017/S1751731111002096
M3 - Journal article
C2 - 22436280
SN - 1751-7311
VL - 6
SP - 633
EP - 640
JO - Animal
JF - Animal
IS - 4
ER -