;PMID: 12234619 ;source_file_1864.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..43] = [t:0..43] ;1)sentence:[e:49..134] = [t:49..134] ;2)section:[e:138..183] = [t:138..183] ;3)section:[e:187..340] = [t:187..340] ;4)sentence:[e:344..516] = [t:344..516] ;5)sentence:[e:517..851] = [t:517..851] ;6)sentence:[e:852..1157] = [t:852..1157] ;7)sentence:[e:1158..1342] = [t:1158..1342] ;8)sentence:[e:1343..1485] = [t:1343..1485] ;9)section:[e:1489..1534] = [t:1489..1534] ;section 0 Span:0..43 ;Biochem Pharmacol. 2002 Oct 1;64(7):1151-6. (SEC (FRAG (NNP:[0..7] Biochem) (NNP:[8..17] Pharmacol) (.:[17..18] .) ('':[19..23] 2002) (NNP:[24..27] Oct) (CD:[28..32] 1;64) (-LRB-:[32..33] -LRB-) (CD:[33..34] 7) (-RRB-:[34..35] -RRB-) (::[35..36] :) (CD:[36..40] 1151) (CD:[40..43] -6.))) ;sentence 1 Span:49..134 ;Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver ;microsomes. ;[63..82]:cyp450:"cytochrome P450 2E1" ;[86..94]:substance:"propofol" (SENT (NP-HLN (NP (NN:[49..59] Inhibition)) (PP (IN:[60..62] of) (NP (NML (NN:[63..73] cytochrome) (NN:[74..78] P450)) (NN:[79..82] 2E1))) (PP (IN:[83..85] by) (NP (NN:[86..94] propofol))) (PP-LOC (IN:[95..97] in) (NP (NP (JJ:[98..103] human) (NML-1 (-NONE-:[103..103] *P*))) (CC:[104..107] and) (NP (JJ:[108..115] porcine) (NML-1 (NN:[116..121] liver) (NNS:[123..133] microsomes))))) (.:[133..134] .))) ;section 2 Span:138..183 ;Lejus C, Fautrel A, Malledant Y, Guillouzo A. (SEC (FRAG (NNP:[138..143] Lejus) (NNP:[144..145] C) (,:[145..146] ,) (NNP:[147..154] Fautrel) (NNP:[155..156] A) (,:[156..157] ,) (NNP:[158..167] Malledant) (NNP:[168..169] Y) (,:[169..170] ,) (NNP:[171..180] Guillouzo) (NNP:[181..182] A) (.:[182..183] .))) ;section 3 Span:187..340 ;INSERM U456, Faculte de Pharmacie, Universite de Rennes 1, Room 2, avenue du ;Prof. Leon Bernard, 35043 Rennes cedex, France. corinne.lejus@chu-nantes.fr (SEC (FRAG (NNP:[187..193] INSERM) (NNP:[194..198] U456) (,:[198..199] ,) (NNP:[200..207] Faculte) (IN:[208..210] de) (NNP:[211..220] Pharmacie) (,:[220..221] ,) (NNP:[222..232] Universite) (IN:[233..235] de) (NNP:[236..242] Rennes) (CD:[243..244] 1) (,:[244..245] ,) (NNP:[246..250] Room) (CD:[251..252] 2) (,:[252..253] ,) (JJ:[254..260] avenue) (IN:[261..263] du) (NN:[265..269] Prof) (.:[269..270] .) (NNP:[271..275] Leon) (NNP:[276..283] Bernard) (,:[283..284] ,) (CD:[285..290] 35043) (NNP:[291..297] Rennes) (NNP:[298..303] cedex) (,:[303..304] ,) (NNP:[305..311] France) (.:[311..312] .) (VBD:[313..320] corinne) (NNS:[320..337] .lejus@chu-nantes) (.:[337..340] .fr))) ;sentence 4 Span:344..516 ;While almost anesthetics are metabolized by the cytochrome P450 (CYP) 3A4, ;some major volatile ones such as halothane and sevoflurane are metabolized ;by CYP2E1 in humans. ;[357..368]:substance:"anesthetics" ;[392..417]:cyp450:"cytochrome P450 (CYP) 3A4" ;[453..462]:substance:"halothane" ;[467..478]:substance:"sevoflurane" ;[498..504]:cyp450:"CYP2E1" (SENT (S (SBAR-ADV (IN:[344..349] While) (S (NP-SBJ-2 (JJ:[350..356] almost) (NNS:[357..368] anesthetics)) (VP (VBP:[369..372] are) (VP (VBN:[373..384] metabolized) (NP-2 (-NONE-:[384..384] *)) (PP (IN:[385..387] by) (NP-LGS (NML (NML (DT:[388..391] the) (NN:[392..402] cytochrome) (NN:[403..407] P450)) (NML (-LRB-:[408..409] -LRB-) (NN:[409..412] CYP) (-RRB-:[412..413] -RRB-))) (NP (NN:[414..417] 3A4)))))))) (,:[417..418] ,) (NP-SBJ-1 (NP (DT:[419..423] some) (JJ:[425..430] major) (JJ:[431..439] volatile) (NNS:[440..444] ones)) (PP (JJ:[445..449] such) (IN:[450..452] as) (NP (NN:[453..462] halothane) (CC:[463..466] and) (NN:[467..478] sevoflurane)))) (VP (VBP:[479..482] are) (VP (VBN:[483..494] metabolized) (NP-1 (-NONE-:[494..494] *)) (PP (IN:[495..497] by) (NP-LGS (NN:[498..504] CYP2E1))) (PP-LOC (IN:[506..508] in) (NP (NNS:[509..515] humans))))) (.:[515..516] .))) ;sentence 5 Span:517..851 ;To determine whether 2,6-diisopropylphenol (propofol), a widely used ;intravenous anesthetic agent, known to inhibit CYP3A4 and CYP1A2, also ;inhibits CYP2E1, 6-OH hydroxylation of chlorzoxazone, a prototypical CYP2E1 ;substrate, was estimated using two pools of human microsomes and one pool of ;porcine microsomes from seven livers. ;[538..559]:substance:"2,6-diisopropylphenol" ;[561..569]:substance:"propofol" ;[599..615]:substance:"anesthetic agent" ;[634..640]:cyp450:"CYP3A4" ;[645..651]:cyp450:"CYP1A2" ;[668..674]:cyp450:"CYP2E1" ;[698..711]:substance:"chlorzoxazone" ;[728..734]:cyp450:"CYP2E1" ;[735..744]:substance:"substrate" (SENT (S (S-PRP (NP-SBJ (-NONE-:[517..517] *)) (VP (TO:[517..519] To) (VP (VB:[520..529] determine) (SBAR (IN:[530..537] whether) (S (NP-SBJ (NP (NP (NP (NN:[538..559] 2,6-diisopropylphenol)) (NP (-LRB-:[560..561] -LRB-) (NN:[561..569] propofol) (-RRB-:[569..570] -RRB-))) (,:[570..571] ,) (NP (DT:[572..573] a) (ADJP (RB:[574..580] widely) (VBN:[581..585] used)) (JJ:[587..598] intravenous) (JJ:[599..609] anesthetic) (NN:[610..615] agent))) (,:[615..616] ,) (VP (VBN:[617..622] known) (S (NP-SBJ (-NONE-:[622..622] *)) (VP (TO:[623..625] to) (VP (VB:[626..633] inhibit) (NP (NN:[634..640] CYP3A4) (CC:[641..644] and) (NN:[645..651] CYP1A2))))))) (,:[651..652] ,) (ADVP (RB:[653..657] also)) (VP (VBZ:[658..666] inhibits) (NP (NN:[668..674] CYP2E1)))))))) (,:[674..675] ,) (NP-SBJ-1 (NP (NN:[676..680] 6-OH) (NN:[681..694] hydroxylation)) (PP (IN:[695..697] of) (NP (NP (NN:[698..711] chlorzoxazone)) (,:[711..712] ,) (NP (DT:[713..714] a) (JJ:[715..727] prototypical) (NN:[728..734] CYP2E1) (NN:[735..744] substrate)))) (,:[744..745] ,)) (VP (VBD:[747..750] was) (VP (VBN:[751..760] estimated) (NP-1 (-NONE-:[760..760] *)) (S-MNR (NP-SBJ (-NONE-:[760..760] *)) (VP (VBG:[761..766] using) (NP (NP (NP (NP (CD:[767..770] two) (NNS:[771..776] pools)) (PP (IN:[777..779] of) (NP (JJ:[780..785] human) (NNS:[786..796] microsomes)))) (CC:[797..800] and) (NP (NP (CD:[801..804] one) (NN:[805..809] pool)) (PP (IN:[810..812] of) (NP (JJ:[813..820] porcine) (NNS:[822..832] microsomes))))) (PP (IN:[833..837] from) (NP (CD:[838..843] seven) (NNS:[844..850] livers)))))))) (.:[850..851] .))) ;sentence 6 Span:852..1157 ;Basal human enzyme activities were characterized by a V(max) of 1426+/-230 ;and 288+/-29 pmol min(-1)mg(-1) protein and a K(m) of 122+/-47 and 149+/-42 ;microM, while the corresponding porcine activities were associated with a ;V(max) of 352+/-42 pmol min(-1)mg(-1) protein and a K(m) of 167+/-38 ;microM. ;[864..870]:substance:"enzyme" ;[907..913]:quantitative-name:"V(max)" ;[917..927]:quantitative-value:"1426+/-230" ;[932..940]:quantitative-value:"288+/-29" ;[941..967]:quantitative-units:"pmol min(-1)mg(-1) protein" ;[974..978]:quantitative-name:"K(m)" ;[983..991]:quantitative-value:"122+/-47" ;[996..1004]:quantitative-value:"149+/-42" ;[1005..1011]:quantitative-units:"microM" ;[1080..1086]:quantitative-name:"V(max)" ;[1090..1098]:quantitative-value:"352+/-42" ;[1099..1125]:quantitative-units:"pmol min(-1)mg(-1) protein" ;[1132..1136]:quantitative-name:"K(m)" ;[1141..1149]:quantitative-value:"167+/-38" ;[1150..1156]:quantitative-units:"microM" (SENT (S (NP-SBJ-4 (JJ:[852..857] Basal) (JJ:[858..863] human) (NN:[864..870] enzyme) (NNS:[871..881] activities)) (VP (VBD:[882..886] were) (VP (VBN:[887..900] characterized) (NP-4 (-NONE-:[900..900] *)) (PP-MNR (IN:[902..904] by) (NP (NP (NP (DT:[905..906] a) (NN:[907..913] V-LRB-max-RRB-)) (PP (IN:[914..916] of) (NP (NP (NML (QP (CD:[917..921] 1426) (SYM:[921..924] +/-) (CD:[924..927] 230)) (NML-3 (-NONE-:[927..927] *P*))) (NML-5 (-NONE-:[927..927] *P*))) (CC:[928..931] and) (NP (NML (QP (CD:[932..935] 288) (SYM:[935..938] +/-) (CD:[938..940] 29)) (NML-3 (NN:[941..945] pmol))) (NML-5 (NN:[946..953] min-LRB--1-RRB-) (NN:[953..959] mg-LRB--1-RRB-) (NN:[960..967] protein)))))) (CC:[968..971] and) (NP (NP (DT:[972..973] a) (NN:[974..978] K-LRB-m-RRB-)) (PP (IN:[979..981] of) (NP (NP (QP (CD:[983..986] 122) (SYM:[986..989] +/-) (CD:[989..991] 47)) (NML-2 (-NONE-:[991..991] *P*))) (CC:[992..995] and) (NP (QP (CD:[996..999] 149) (SYM:[999..1002] +/-) (CD:[1002..1004] 42)) (NML-2 (NN:[1005..1011] microM)))))))) (,:[1011..1012] ,) (SBAR-ADV (IN:[1013..1018] while) (S (NP-SBJ-1 (DT:[1019..1022] the) (VBG:[1023..1036] corresponding) (JJ:[1037..1044] porcine) (NNS:[1045..1055] activities)) (VP (VBD:[1056..1060] were) (VP (VBN:[1062..1072] associated) (NP-1 (-NONE-:[1072..1072] *)) (PP-CLR (IN:[1073..1077] with) (NP (NP (NP (DT:[1078..1079] a) (NN:[1080..1086] V-LRB-max-RRB-)) (PP (IN:[1087..1089] of) (NP (NML (QP (CD:[1090..1093] 352) (SYM:[1093..1096] +/-) (CD:[1096..1098] 42)) (NN:[1099..1103] pmol)) (NN:[1104..1111] min-LRB--1-RRB-) (NN:[1111..1117] mg-LRB--1-RRB-) (NN:[1118..1125] protein)))) (CC:[1126..1129] and) (NP (NP (DT:[1130..1131] a) (NN:[1132..1136] K-LRB-m-RRB-)) (PP (IN:[1137..1139] of) (NP (QP (CD:[1141..1144] 167) (SYM:[1144..1147] +/-) (CD:[1147..1149] 38)) (NN:[1150..1156] microM)))))))))))) (.:[1156..1157] .))) ;sentence 7 Span:1158..1342 ;A competitive inhibition of CYP2E1 by propofol was observed with low ;inhibition constants in the therapeutic range in both porcine (19 microM) ;and human (48 microM) liver microsomes. ;[1186..1192]:cyp450:"CYP2E1" ;[1196..1204]:substance:"propofol" ;[1291..1293]:quantitative-value:"19" ;[1295..1301]:quantitative-units:"microM" ;[1314..1316]:quantitative-value:"48" ;[1317..1323]:quantitative-units:"microM" (SENT (S (NP-SBJ-2 (NP (DT:[1158..1159] A) (JJ:[1160..1171] competitive) (NN:[1172..1182] inhibition)) (PP (IN:[1183..1185] of) (NP (NN:[1186..1192] CYP2E1))) (PP (IN:[1193..1195] by) (NP (NN:[1196..1204] propofol)))) (VP (VBD:[1205..1208] was) (VP (VBN:[1209..1217] observed) (NP-2 (-NONE-:[1217..1217] *)) (PP (IN:[1219..1223] with) (NP (NP (JJ:[1224..1227] low) (NN:[1228..1238] inhibition) (NNS:[1239..1248] constants)) (PP (IN:[1249..1251] in) (NP (DT:[1252..1255] the) (JJ:[1256..1267] therapeutic) (NN:[1268..1273] range))))) (PP-LOC (IN:[1274..1276] in) (NP (CC:[1277..1281] both) (NP (JJ:[1282..1289] porcine) (PRN (-LRB-:[1290..1291] -LRB-) (NP (CD:[1291..1293] 19) (NN:[1295..1301] microM)) (-RRB-:[1301..1302] -RRB-)) (NML-1 (-NONE-:[1302..1302] *P*))) (CC:[1303..1306] and) (NP (JJ:[1307..1312] human) (PRN (-LRB-:[1313..1314] -LRB-) (NP (CD:[1314..1316] 48) (NN:[1317..1323] microM)) (-RRB-:[1323..1324] -RRB-)) (NML-1 (NN:[1325..1330] liver) (NNS:[1331..1341] microsomes))))))) (.:[1341..1342] .))) ;sentence 8 Span:1343..1485 ;These in vitro results suggest that propofol could have a protective effect ;on toxic metabolite activation of compounds catalyzed by CYP2E1. ;[1380..1388]:substance:"propofol" ;[1429..1439]:substance:"metabolite" ;[1478..1484]:cyp450:"CYP2E1" (SENT (S (NP-SBJ (DT:[1343..1348] These) (ADJP (FW:[1349..1351] in) (FW:[1352..1357] vitro)) (NNS:[1358..1365] results)) (VP (VBP:[1366..1373] suggest) (SBAR (IN:[1375..1379] that) (S (NP-SBJ (NN:[1380..1388] propofol)) (VP (MD:[1389..1394] could) (VP (VB:[1395..1399] have) (NP (DT:[1400..1401] a) (JJ:[1402..1412] protective) (NN:[1413..1419] effect)) (PP (IN:[1420..1422] on) (NP (NP (JJ:[1423..1428] toxic) (NN:[1429..1439] metabolite) (NN:[1440..1450] activation)) (PP (IN:[1451..1453] of) (NP (NP (NNS:[1455..1464] compounds)) (VP (VBN:[1465..1474] catalyzed) (NP (-NONE-:[1474..1474] *)) (PP (IN:[1475..1477] by) (NP-LGS (NN:[1478..1484] CYP2E1))))))))))))) (.:[1484..1485] .))) ;section 9 Span:1489..1534 ;PMID: 12234619 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1489..1493] PMID) (::[1493..1494] :) (CD:[1495..1503] 12234619) (NN:[1504..1505] -LSB-) (NNP:[1505..1511] PubMed) (::[1512..1513] -) (NN:[1514..1521] indexed) (IN:[1522..1525] for) (NNP:[1526..1534] MEDLINE-RSB-)))