;PMID: 1755509 ;source_file_1903.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..44] = [t:0..44] ;1)sentence:[e:50..186] = [t:50..186] ;2)section:[e:190..229] = [t:190..229] ;3)section:[e:233..311] = [t:233..311] ;4)sentence:[e:315..395] = [t:315..395] ;5)sentence:[e:397..600] = [t:397..600] ;6)sentence:[e:601..777] = [t:601..777] ;7)sentence:[e:778..896] = [t:778..896] ;8)sentence:[e:897..1182] = [t:897..1182] ;9)sentence:[e:1184..1442] = [t:1184..1442] ;10)sentence:[e:1443..1597] = [t:1443..1597] ;11)sentence:[e:1598..1994] = [t:1598..1994] ;12)section:[e:1998..2042] = [t:1998..2042] ;Token/POS Errors ;ERROR_Token in entity file but not tree[27..30] Oct ;ERROR_Token in entity file but not tree[30..31] ; ;ERROR_Token in entity file but not tree[31..33] 15 ;ERROR_Token in entity file but not tree[36..37] : ;ERROR_Token in entity file but not tree[37..40] 779 ;ERROR_Token in entity file but not tree[40..41] - ;ERROR_Token in entity file but not tree[41..43] 84 ;ERROR_Token in entity file but not tree[227..228] C ;ERROR_Token in entity file but not tree[228..229] . ;ERROR_Token in entity file but not tree[2034..2041] MEDLINE ;ERROR_Token in entity file but not tree[2041..2042] ] ;ERROR_Token in tree file but not entity[27..33] Oct;15 ;ERROR_Token in tree file but not entity[36..40] :779 ;ERROR_Token in tree file but not entity[40..43] -84 ;ERROR_POS mismatch [176..185] t:NN e:CD P-450IIE1 ;ERROR_Token in tree file but not entity[227..229] C. ;ERROR_POS mismatch [886..895] t:NN e:CD P-450IIE1 ;ERROR_Token in tree file but not entity[2034..2042] MEDLINE] ;section 0 Span:0..44 ;Alcohol Clin Exp Res. 1991 Oct;15(5):779-84. (SEC (FRAG (NNP:[0..7] Alcohol) (NNP:[8..12] Clin) (NNP:[13..16] Exp) (NNP:[17..20] Res) (.:[20..21] .) (CD:[22..26] 1991) (.:[27..33] Oct;15) (-LRB-:[33..34] -LRB-) (CD:[34..35] 5) (-RRB-:[35..36] -RRB-) (CD:[36..40] :779) (CD:[40..43] -84) (.:[43..44] .))) ;sentence 1 Span:50..186 ;Ethanol-induced enhancement of cocaine bioactivation and irreversible protein ; binding: evidence against a role of cytochrome P-450IIE1. ;[50..57]:substance:"Ethanol" ;[81..88]:substance:"cocaine" ;[120..127]:substance:"protein" ;[165..185]:cyp450:"cytochrome P-450IIE1" (SENT (NP-HLN (NP (NP (ADJP (NN:[50..57] Ethanol) (HYPH:[57..58] -) (VBN:[58..65] induced)) (NN:[66..77] enhancement)) (PP (IN:[78..80] of) (NP (NP (NML-1 (NN:[81..88] cocaine)) (NN:[89..102] bioactivation)) (CC:[103..106] and) (NP (NML-1 (-NONE-:[106..106] *P*)) (JJ:[107..119] irreversible) (NN:[120..127] protein) (NN:[129..136] binding))))) (::[136..137] :) (NP (NP (NN:[138..146] evidence)) (PP (IN:[147..154] against) (NP (NP (DT:[155..156] a) (NN:[157..161] role)) (PP (IN:[162..164] of) (NP (NN:[165..175] cytochrome) (NN:[176..185] P-450IIE1)))))) (.:[185..186] .))) ;section 2 Span:190..229 ;Boelsterli UA, Atanasoski S, Goldlin C. (SEC (FRAG (NNP:[190..200] Boelsterli) (NNP:[201..203] UA) (,:[203..204] ,) (NNP:[205..215] Atanasoski) (NNP:[216..217] S) (,:[217..218] ,) (NNP:[219..226] Goldlin) (NNP:[227..229] C.))) ;section 3 Span:233..311 ;Institute of Toxicology, Swiss Federal Institute of Technology, ;Schwerzenbach. (SEC (FRAG (NNP:[233..242] Institute) (IN:[243..245] of) (NNP:[246..256] Toxicology) (,:[256..257] ,) (NNP:[258..263] Swiss) (NNP:[264..271] Federal) (NNP:[272..281] Institute) (IN:[282..284] of) (NNP:[285..295] Technology) (,:[295..296] ,) (NNP:[297..310] Schwerzenbach) (.:[310..311] .))) ;sentence 4 Span:315..395 ;Chronic ethanol consumption potentiates cocaine-induced liver injury in ;rodents. ;[323..330]:substance:"ethanol" ;[355..362]:substance:"cocaine" (SENT (S (NP-SBJ (JJ:[315..322] Chronic) (NN:[323..330] ethanol) (NN:[331..342] consumption)) (VP (VBZ:[343..354] potentiates) (NP (ADJP (NN:[355..362] cocaine) (HYPH:[362..363] -) (VBN:[363..370] induced)) (NN:[371..376] liver) (NN:[377..383] injury)) (PP-LOC (IN:[384..386] in) (NML (NNS:[387..394] rodents)))) (.:[394..395] .))) ;sentence 5 Span:397..600 ;Since cocaine has to be bioactivated by a cytochrome P-450-dependent ;N-oxidative pathway to exert its hepatotoxic effects, we studied the role of ;the ethanol-inducible P-450IIE1 for cocaine metabolism. ;[403..410]:substance:"cocaine" ;[439..455]:cyp450:"cytochrome P-450" ;[549..556]:substance:"ethanol" ;[567..576]:cyp450:"P-450IIE1" ;[581..588]:substance:"cocaine" (SENT (S (SBAR-ADV (IN:[397..402] Since) (S (NP-SBJ-1 (NN:[403..410] cocaine)) (VP (VBZ:[411..414] has) (S (NP-SBJ-1 (-NONE-:[414..414] *)) (VP (TO:[415..417] to) (VP (VB:[418..420] be) (VP (VBN:[421..433] bioactivated) (NP-1 (-NONE-:[433..433] *)) (PP (IN:[434..436] by) (NP-LGS (DT:[437..438] a) (ADJP (NML (NN:[439..449] cytochrome) (NN:[450..455] P-450)) (HYPH:[455..456] -) (JJ:[456..465] dependent)) (JJ:[466..477] N-oxidative) (NN:[479..486] pathway))) (S-PRP (NP-SBJ-1 (-NONE-:[486..486] *)) (VP (TO:[487..489] to) (VP (VB:[490..495] exert) (NP (PRP$:[496..499] its) (JJ:[500..511] hepatotoxic) (NNS:[512..519] effects)))))))))))) (,:[519..520] ,) (NP-SBJ (PRP:[521..523] we)) (VP (VBD:[524..531] studied) (NP (NP (DT:[532..535] the) (NN:[536..540] role)) (PP (IN:[541..543] of) (NP (DT:[544..547] the) (ADJP (NN:[549..556] ethanol) (HYPH:[556..557] -) (JJ:[557..566] inducible)) (NN:[567..576] P-450IIE1))) (PP (IN:[577..580] for) (NP (NN:[581..588] cocaine) (NN:[589..599] metabolism))))) (.:[599..600] .))) ;sentence 6 Span:601..777 ;Male Sprague-Dawley rats were pretreated with either a liquid diet ;containing ethanol (30% of calories) for 4 weeks or injected with pyrazole ;(200 mg/kg/day, ip, for 3 days). ;[657..663]:substance:"liquid" ;[680..687]:substance:"ethanol" ;[689..692]:quantitative-value:"30%" ;[711..712]:quantitative-value:"4" ;[713..718]:quantitative-units:"weeks" ;[736..744]:substance:"pyrazole" ;[746..749]:quantitative-value:"200" ;[750..759]:quantitative-units:"mg/kg/day" ;[769..770]:quantitative-value:"3" ;[771..775]:quantitative-units:"days" (SENT (S (NP-SBJ-1 (JJ:[601..605] Male) (NML (NNP:[606..613] Sprague) (HYPH:[613..614] -) (NNP:[614..620] Dawley)) (NNS:[621..625] rats)) (VP (VBD:[627..631] were) (VP (VP (VBN:[632..642] pretreated) (NP-1 (-NONE-:[642..642] *)) (PP-MNR (IN:[643..647] with) (NP (CC:[648..654] either) (NP (DT:[655..656] a) (NN:[657..663] liquid) (NN:[664..668] diet)) (VP (VBG:[669..679] containing) (NP (NP (NN:[680..687] ethanol)) (PRN (-LRB-:[688..689] -LRB-) (NP (NP (CD:[689..691] 30) (NN:[691..692] %)) (PP (IN:[693..695] of) (NP (NNS:[696..704] calories)))) (-RRB-:[704..705] -RRB-)))))) (PP-TMP (IN:[707..710] for) (NP (CD:[711..712] 4) (NNS:[713..718] weeks)))) (CC:[719..721] or) (VP (VBN:[722..730] injected) (NP-1 (-NONE-:[730..730] *)) (PP-MNR (IN:[731..735] with) (NP (NP (NN:[736..744] pyrazole)) (PRN (-LRB-:[745..746] -LRB-) (FRAG (NP (NP (CD:[746..749] 200) (NN:[750..752] mg)) (PP (SYM:[752..753] /) (NP (NN:[753..755] kg))) (PP (SYM:[755..756] /) (NP (NN:[756..759] day)))) (,:[759..760] ,) (ADVP (RB:[761..763] ip)) (,:[763..764] ,) (PP-TMP (IN:[765..768] for) (NP (CD:[769..770] 3) (NNS:[771..775] days)))) (-RRB-:[775..776] -RRB-))))))) (.:[776..777] .))) ;sentence 7 Span:778..896 ;Both agents induced microsomal p-nitrophenol hydroxylation which is a probe ;for the catalytic activity of P-450IIE1. ;[784..790]:substance:"agents" ;[810..823]:substance:"p-nitrophenol" ;[886..895]:cyp450:"P-450IIE1" (SENT (S (NP-SBJ (DT:[778..782] Both) (NNS:[784..790] agents)) (VP (VBD:[791..798] induced) (NP (NP (JJ:[799..809] microsomal) (NN:[810..823] p-nitrophenol) (NN:[824..837] hydroxylation)) (SBAR (WHNP-1 (WDT:[838..843] which)) (S (NP-SBJ-1 (-NONE-:[843..843] *T*)) (VP (VBZ:[844..846] is) (NP-PRD (NP (DT:[847..848] a) (NN:[849..854] probe)) (PP (IN:[855..858] for) (NP (NP (DT:[859..862] the) (JJ:[864..873] catalytic) (NN:[874..882] activity)) (PP (IN:[883..885] of) (NP (NN:[886..895] P-450IIE1))))))))))) (.:[895..896] .))) ;sentence 8 Span:897..1182 ;However, only ethanol, but not pyrazole, increased both microsomal cocaine ;N-demethylase activity (by 47%) and the extent of irreversible binding of ;[3H]-cocaine to microsomal proteins (by 100%), which was taken as a ;quantitative endpoint for the formation of a reactive metabolite. ;[911..918]:substance:"ethanol" ;[928..936]:substance:"pyrazole" ;[965..986]:substance:"cocaine N-demethylase" ;[1000..1003]:quantitative-value:"47%" ;[1048..1060]:substance:"[3H]-cocaine" ;[1075..1083]:substance:"proteins" ;[1088..1092]:quantitative-value:"100%" ;[1171..1181]:substance:"metabolite" (SENT (S (ADVP (RB:[897..904] However)) (,:[904..905] ,) (NP-SBJ (NP (RB:[906..910] only) (NN:[911..918] ethanol)) (,:[918..919] ,) (CONJP (CC:[920..923] but) (RB:[924..927] not)) (NP (NN:[928..936] pyrazole))) (,:[936..937] ,) (VP (VBD:[939..948] increased) (NP (CC:[949..953] both) (NP (NP (JJ:[954..964] microsomal) (NML (NN:[965..972] cocaine) (NN:[973..986] N-demethylase)) (NN:[987..995] activity)) (PRN (-LRB-:[996..997] -LRB-) (PP-EXT (IN:[997..999] by) (NP (CD:[1000..1002] 47) (NN:[1002..1003] %))) (-RRB-:[1003..1004] -RRB-))) (CC:[1005..1008] and) (NP (NP (DT:[1009..1012] the) (NN:[1013..1019] extent)) (PP (IN:[1021..1023] of) (NP (NP (JJ:[1024..1036] irreversible) (NN:[1037..1044] binding)) (PP (IN:[1045..1047] of) (NP (NN:[1048..1060] -LSB-3H-RSB--cocaine))) (PP (TO:[1061..1063] to) (NP (JJ:[1064..1074] microsomal) (NNS:[1075..1083] proteins))) (PRN (-LRB-:[1084..1085] -LRB-) (PP-EXT (IN:[1085..1087] by) (NP (CD:[1088..1091] 100) (NN:[1091..1092] %))) (-RRB-:[1092..1093] -RRB-)))))) (,:[1093..1094] ,) (SBAR-ADV (WHNP-1 (WDT:[1095..1100] which)) (S (NP-SBJ-1 (-NONE-:[1100..1100] *T*)) (VP (VBD:[1102..1105] was) (VP (VBN:[1106..1111] taken) (NP-1 (-NONE-:[1111..1111] *)) (PP-CLR (IN:[1112..1114] as) (NP (NP (DT:[1115..1116] a) (JJ:[1117..1129] quantitative) (NN:[1130..1138] endpoint)) (PP (IN:[1139..1142] for) (NP (NP (DT:[1143..1146] the) (NN:[1147..1156] formation)) (PP (IN:[1157..1159] of) (NP (DT:[1160..1161] a) (JJ:[1162..1170] reactive) (NN:[1171..1181] metabolite)))))))))))) (.:[1181..1182] .))) ;sentence 9 Span:1184..1442 ;Cocaine N-demethylation and irreversible protein binding of cocaine were not ;inhibited by P-450IIE1 isozyme-selective substrates, nor was the rate of ;cocaine metabolism and binding decreased by functionally active polyclonal ;anti-rat P-450IIE1 antibodies. ;[1184..1191]:substance:"Cocaine" ;[1225..1232]:substance:"protein" ;[1244..1251]:substance:"cocaine" ;[1275..1292]:cyp450:"P-450IIE1 isozyme" ;[1303..1313]:substance:"substrates" ;[1335..1342]:substance:"cocaine" ;[1400..1441]:substance:"polyclonal anti-rat P-450IIE1 antibodies" (SENT (S (S (NP-SBJ-3 (NP (NN:[1184..1191] Cocaine) (NN:[1192..1207] N-demethylation)) (CC:[1208..1211] and) (NP (NP (JJ:[1212..1224] irreversible) (NN:[1225..1232] protein) (NN:[1233..1240] binding)) (PP (IN:[1241..1243] of) (NP (NN:[1244..1251] cocaine))))) (VP (VBD:[1252..1256] were) (RB:[1257..1260] not) (VP (VBN:[1262..1271] inhibited) (NP-3 (-NONE-:[1271..1271] *)) (PP (IN:[1272..1274] by) (NP-LGS (ADJP (NML (NN:[1275..1284] P-450IIE1) (NN:[1285..1292] isozyme)) (HYPH:[1292..1293] -) (JJ:[1293..1302] selective)) (NNS:[1303..1313] substrates)))))) (,:[1313..1314] ,) (CC:[1315..1318] nor) (SINV (VBD:[1319..1322] was) (NP-SBJ-2 (NP (DT:[1323..1326] the) (NN:[1327..1331] rate)) (PP (IN:[1332..1334] of) (NP (NP (NML-1 (NN:[1335..1342] cocaine)) (NN:[1344..1354] metabolism)) (CC:[1355..1358] and) (NP (NML-1 (-NONE-:[1358..1358] *P*)) (NN:[1359..1366] binding))))) (VP (VBN:[1367..1376] decreased) (NP-2 (-NONE-:[1376..1376] *)) (PP (IN:[1377..1379] by) (NP-LGS (ADJP (RB:[1380..1392] functionally) (JJ:[1393..1399] active)) (JJ:[1400..1410] polyclonal) (NML (AFX:[1411..1415] anti) (HYPH:[1415..1416] -) (NN:[1416..1419] rat) (NN:[1421..1430] P-450IIE1)) (NNS:[1431..1441] antibodies))))) (.:[1441..1442] .))) ;sentence 10 Span:1443..1597 ;Furthermore, pyrazole pretreatment sensitized cultured hepatocytes to the ;glutathione-dependent cytotoxic effects of nontoxic concentrations of ;cocaine. ;[1456..1464]:substance:"pyrazole" ;[1518..1529]:substance:"glutathione" ;[1589..1596]:substance:"cocaine" (SENT (S (ADVP (RB:[1443..1454] Furthermore)) (,:[1454..1455] ,) (NP-SBJ (NN:[1456..1464] pyrazole) (NN:[1465..1477] pretreatment)) (VP (VBD:[1478..1488] sensitized) (NP (VBN:[1489..1497] cultured) (NNS:[1499..1510] hepatocytes)) (PP-CLR (TO:[1511..1513] to) (NP (NP (DT:[1514..1517] the) (ADJP (NN:[1518..1529] glutathione) (HYPH:[1529..1530] -) (JJ:[1530..1539] dependent)) (JJ:[1540..1549] cytotoxic) (NNS:[1550..1557] effects)) (PP (IN:[1558..1560] of) (NP (NP (JJ:[1561..1569] nontoxic) (NNS:[1571..1585] concentrations)) (PP (IN:[1586..1588] of) (NP (NN:[1589..1596] cocaine)))))))) (.:[1596..1597] .))) ;sentence 11 Span:1598..1994 ;These results indicate that (a) cocaine is not a major substrate for the ;ethanol-inducible P-450IIE1, (b) the enhancing effects of ethanol on cocaine ;bioactivation may be due to induction of other P-450 isoforms, and (c) ;induction of P-450IIE1 may potentiate cocaine-induced hepatocellular ;toxicity in vitro independently of cocaine metabolism, e.g., by ;P-450IIE1-dependent oxidative stress. ;[1630..1637]:substance:"cocaine" ;[1654..1663]:substance:"substrate" ;[1672..1679]:substance:"ethanol" ;[1690..1699]:cyp450:"P-450IIE1" ;[1731..1738]:substance:"ethanol" ;[1742..1749]:substance:"cocaine" ;[1797..1812]:cyp450:"P-450 isoforms" ;[1835..1844]:cyp450:"P-450IIE1" ;[1860..1867]:substance:"cocaine" ;[1927..1934]:substance:"cocaine" ;[1957..1966]:cyp450:"P-450IIE1" (SENT (S (NP-SBJ (DT:[1598..1603] These) (NNS:[1604..1611] results)) (VP (VBP:[1612..1620] indicate) (SBAR (IN:[1621..1625] that) (S (S (LST (LS:[1626..1629] -LRB-a-RRB-)) (NP-SBJ (NN:[1630..1637] cocaine)) (VP (VBZ:[1638..1640] is) (RB:[1641..1644] not) (NP-PRD (NP (DT:[1645..1646] a) (JJ:[1648..1653] major) (NN:[1654..1663] substrate)) (PP (IN:[1664..1667] for) (NP (DT:[1668..1671] the) (ADJP (NN:[1672..1679] ethanol) (HYPH:[1679..1680] -) (JJ:[1680..1689] inducible)) (NN:[1690..1699] P-450IIE1)))))) (,:[1699..1700] ,) (S (LST (LS:[1701..1704] -LRB-b-RRB-)) (NP-SBJ (NP (DT:[1705..1708] the) (VBG:[1709..1718] enhancing) (NNS:[1719..1726] effects)) (PP (IN:[1728..1730] of) (NP (NN:[1731..1738] ethanol))) (PP (IN:[1739..1741] on) (NP (NN:[1742..1749] cocaine) (NN:[1750..1763] bioactivation)))) (VP (MD:[1764..1767] may) (VP (VB:[1768..1770] be) (PP-PRD (IN:[1771..1774] due) (PP (TO:[1775..1777] to) (NP (NP (NN:[1778..1787] induction)) (PP (IN:[1788..1790] of) (NP (JJ:[1791..1796] other) (NN:[1797..1802] P-450) (NNS:[1804..1812] isoforms))))))))) (,:[1812..1813] ,) (CC:[1814..1817] and) (S (LST (LS:[1818..1821] -LRB-c-RRB-)) (NP-SBJ (NP (NN:[1822..1831] induction)) (PP (IN:[1832..1834] of) (NP (NN:[1835..1844] P-450IIE1)))) (VP (MD:[1845..1848] may) (VP (VB:[1849..1859] potentiate) (NP (ADJP (NN:[1860..1867] cocaine) (HYPH:[1867..1868] -) (VBN:[1868..1875] induced)) (JJ:[1877..1891] hepatocellular) (NN:[1892..1900] toxicity)) (ADVP (FW:[1901..1903] in) (FW:[1904..1909] vitro)) (ADVP-MNR (RB:[1910..1923] independently) (PP (IN:[1924..1926] of) (NP (NN:[1927..1934] cocaine) (NN:[1935..1945] metabolism)))) (,:[1945..1946] ,) (PP-MNR (ADVP (FW:[1947..1951] e.g.)) (,:[1951..1952] ,) (IN:[1953..1955] by) (NP (ADJP (NN:[1957..1966] P-450IIE1) (HYPH:[1966..1967] -) (JJ:[1967..1976] dependent)) (JJ:[1977..1986] oxidative) (NN:[1987..1993] stress))))))))) (.:[1993..1994] .))) ;section 12 Span:1998..2042 ;PMID: 1755509 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1998..2002] PMID) (::[2002..2003] :) (CD:[2004..2011] 1755509) (NN:[2012..2013] -LSB-) (NNP:[2013..2019] PubMed) (::[2020..2021] -) (NN:[2022..2029] indexed) (IN:[2030..2033] for) (NNP:[2034..2042] MEDLINE-RSB-)))