;PMID: 3878657 ;source_file_1926.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..54] = [t:0..54] ;1)sentence:[e:60..195] = [t:60..195] ;2)section:[e:199..234] = [t:199..234] ;3)sentence:[e:238..407] = [t:238..407] ;4)sentence:[e:408..643] = [t:408..643] ;5)sentence:[e:644..794] = [t:644..794] ;6)sentence:[e:796..1073] = [t:796..1073] ;7)sentence:[e:1074..1135] = [t:1074..1135] ;8)sentence:[e:1136..1303] = [t:1136..1303] ;9)sentence:[e:1304..1486] = [t:1304..1486] ;10)section:[e:1490..1534] = [t:1490..1534] ;section 0 Span:0..54 ;Acta Pharmacol Toxicol (Copenh). 1985 Oct;57(4):250-4. (SEC (FRAG (NNP:[0..4] Acta) (NNP:[5..14] Pharmacol) (NNP:[15..22] Toxicol) (-LRB-:[23..24] -LRB-) (NN:[24..30] Copenh) (-RRB-:[30..31] -RRB-) (.:[31..32] .) (CD:[33..37] 1985) (.:[38..44] Oct;57) (-LRB-:[44..45] -LRB-) (CD:[45..46] 4) (-RRB-:[46..47] -RRB-) (CD:[47..54] :250-4.))) ;sentence 1 Span:60..195 ;Inhibition by methylglyoxal bis(guanylhydrazone) of drug oxidation reactions ;catalyzed by mouse liver microsomes in vivo and in vitro. ;[74..108]:substance:"methylglyoxal bis(guanylhydrazone)" ;[112..116]:substance:"drug" (SENT (NP-HLN (NP (NN:[60..70] Inhibition)) (PP (IN:[71..73] by) (NP (NN:[74..87] methylglyoxal) (NN:[88..108] bis-LRB-guanylhydrazone-RRB-))) (PP (IN:[109..111] of) (NP (NP (NN:[112..116] drug) (NN:[117..126] oxidation) (NNS:[127..136] reactions)) (VP (VBN:[138..147] catalyzed) (NP (-NONE-:[147..147] *)) (PP (IN:[148..150] by) (NP-LGS (NN:[151..156] mouse) (NN:[157..162] liver) (NNS:[163..173] microsomes))) (ADVP (ADVP (FW:[174..176] in) (FW:[177..181] vivo)) (CC:[182..185] and) (ADVP (FW:[186..188] in) (FW:[189..194] vitro)))))) (.:[194..195] .))) ;section 2 Span:199..234 ;Kaipainen PM, Karvonen EH, Poso HJ. (SEC (FRAG (NNP:[199..208] Kaipainen) (NNP:[209..211] PM) (,:[211..212] ,) (NNP:[213..221] Karvonen) (NNP:[222..224] EH) (,:[224..225] ,) (NNP:[226..230] Poso) (NNP:[231..234] HJ.))) ;sentence 3 Span:238..407 ;The activity of coumarin 7-hydroxylase (coumarin 7-hydroxylation) was ;inhibited in B6 mouse liver after a single injection of methylglyoxal ;bis(guanylhydrazone (MGBG). ;[254..276]:cyp450:"coumarin 7-hydroxylase" ;[278..286]:substance:"coumarin" ;[365..398]:substance:"methylglyoxal bis(guanylhydrazone" ;[401..405]:substance:"MGBG" (SENT (S (NP-SBJ-1 (NP (DT:[238..241] The) (NN:[242..250] activity)) (PP (IN:[251..253] of) (NP (NP (NN:[254..262] coumarin) (NN:[263..276] 7-hydroxylase)) (NP (-LRB-:[277..278] -LRB-) (NN:[278..286] coumarin) (NN:[287..302] 7-hydroxylation) (-RRB-:[302..303] -RRB-))))) (VP (VBD:[304..307] was) (VP (VBN:[308..317] inhibited) (NP-1 (-NONE-:[317..317] *)) (PP-LOC (IN:[319..321] in) (NP (NN:[322..324] B6) (NN:[325..330] mouse) (NN:[331..336] liver))) (PP-TMP (IN:[337..342] after) (NP (NP (DT:[343..344] a) (JJ:[345..351] single) (NN:[352..361] injection)) (PP (IN:[362..364] of) (NP (NP (NN:[365..378] methylglyoxal) (NN:[379..398] bis-LRB-guanylhydrazone)) (NP (-LRB-:[400..401] -LRB-) (NN:[401..405] MGBG) (-RRB-:[405..406] -RRB-)))))))) (.:[406..407] .))) ;sentence 4 Span:408..643 ;The decrease in the activity in vivo was greatest (70%) one day after the ;drug injection and the hydroxylase activity in microsomal fraction prepared ;from livers of MGBG-treated B6 mice was still 25% decreased 5 days after the ;drug. ;[459..462]:quantitative-value:"70%" ;[464..467]:quantitative-value:"one" ;[468..471]:quantitative-units:"day" ;[483..487]:substance:"drug" ;[506..517]:substance:"hydroxylase" ;[575..579]:substance:"MGBG" ;[606..609]:quantitative-value:"25%" ;[620..621]:quantitative-value:"5" ;[622..626]:quantitative-units:"days" ;[638..642]:substance:"drug" (SENT (S (S (NP-SBJ (NP (DT:[408..411] The) (NN:[412..420] decrease)) (PP (IN:[421..423] in) (NP (DT:[424..427] the) (NN:[428..436] activity))) (ADJP (FW:[437..439] in) (FW:[440..444] vivo))) (VP (VBD:[445..448] was) (ADJP-PRD (JJS:[449..457] greatest) (PRN (-LRB-:[458..459] -LRB-) (NP (CD:[459..461] 70) (NN:[461..462] %)) (-RRB-:[462..463] -RRB-))) (PP-TMP (NP-ADV (CD:[464..467] one) (NN:[468..471] day)) (IN:[472..477] after) (NP (DT:[479..482] the) (NN:[483..487] drug) (NN:[488..497] injection))))) (CC:[498..501] and) (S (NP-SBJ-1 (NP (DT:[502..505] the) (NN:[506..517] hydroxylase) (NN:[518..526] activity)) (PP (IN:[527..529] in) (NP (NP (JJ:[530..540] microsomal) (NN:[541..549] fraction)) (VP (VBN:[550..558] prepared) (NP (-NONE-:[558..558] *)) (PP (IN:[560..564] from) (NP (NP (NNS:[565..571] livers)) (PP (IN:[572..574] of) (NP (ADJP (NN:[575..579] MGBG) (HYPH:[579..580] -) (VBN:[580..587] treated)) (NN:[588..590] B6) (NNS:[591..595] mice))))))))) (VP (VBD:[596..599] was) (ADVP (RB:[600..605] still)) (NP-EXT (CD:[606..608] 25) (NN:[608..609] %)) (VP (VBN:[610..619] decreased) (NP-1 (-NONE-:[619..619] *)) (PP-TMP (NP-ADV (CD:[620..621] 5) (NNS:[622..626] days)) (IN:[627..632] after) (NP (DT:[633..636] the) (NN:[638..642] drug)))))) (.:[642..643] .))) ;sentence 5 Span:644..794 ;The amount of cytochrome P-450 also was decreased in MGBG-treated livers ;with the same time-dependency as the inhibition of coumarin 7-hydroxylation. ;[658..674]:cyp450:"cytochrome P-450" ;[697..701]:substance:"MGBG" ;[769..777]:substance:"coumarin" (SENT (S (NP-SBJ-1 (NP (DT:[644..647] The) (NN:[648..654] amount)) (PP (IN:[655..657] of) (NP (NN:[658..668] cytochrome) (NN:[669..674] P-450)))) (ADVP (RB:[675..679] also)) (VP (VBD:[680..683] was) (VP (VBN:[684..693] decreased) (NP-1 (-NONE-:[693..693] *)) (PP-LOC (IN:[694..696] in) (NP (NP (ADJP (NN:[697..701] MGBG) (HYPH:[701..702] -) (VBN:[702..709] treated)) (NNS:[710..716] livers)) (PP (IN:[718..722] with) (NP (NP (DT:[723..726] the) (JJ:[727..731] same) (NN:[732..736] time) (HYPH:[736..737] -) (NN:[737..747] dependency)) (PP (IN:[748..750] as) (NP (NP (DT:[751..754] the) (NN:[755..765] inhibition)) (PP (IN:[766..768] of) (NP (NN:[769..777] coumarin) (NN:[778..793] 7-hydroxylation))))))))))) (.:[793..794] .))) ;sentence 6 Span:796..1073 ;MGBG and its close derivative ;1,1'-[methylethanediylidene)dinitrilo)bis(3-aminoguanidine) (MBAG) inhibited ;the activity in vitro of coumarin 7-hydroxylase, benzo(a)pyrene hydroxylase ;and 7-ethoxy 0-de-ethylase when microsomes were prepared from livers of ;untreated B6 mice. ;[796..800]:substance:"MGBG" ;[815..825]:substance:"derivative" ;[827..886]:substance:"1,1'-[methylethanediylidene)dinitrilo)bis(3-aminoguanid ;ine)" ;[888..892]:substance:"MBAG" ;[930..952]:cyp450:"coumarin 7-hydroxylase" ;[954..980]:cyp450:"benzo(a)pyrene hydroxylase" ;[986..1008]:substance:"7-ethoxy 0-de-ethylase" (SENT (S (NP-SBJ (NP (NN:[796..800] MGBG)) (CC:[801..804] and) (NP (NP (PRP$:[805..808] its) (JJ:[809..814] close) (NN:[815..825] derivative)) (NP (NP (NN:[827..886] 1,1'--LSB-methylethanediylidene-RRB-dinitrilo-RRB-bis-LRB-3-aminoguanidine-RRB-)) (NP (-LRB-:[887..888] -LRB-) (NN:[888..892] MBAG) (-RRB-:[892..893] -RRB-))))) (VP (VBD:[894..903] inhibited) (NP (NP (DT:[904..907] the) (NN:[909..917] activity)) (ADJP (FW:[918..920] in) (FW:[921..926] vitro)) (PP (IN:[927..929] of) (NP (NP (NN:[930..938] coumarin) (NN:[939..952] 7-hydroxylase)) (,:[952..953] ,) (NP (NN:[954..968] benzo-LRB-a-RRB-pyrene) (NN:[969..980] hydroxylase)) (CC:[981..984] and) (NP (NN:[986..994] 7-ethoxy) (NN:[995..1008] 0-de-ethylase))))) (SBAR-ADV (WHADVP-1 (WRB:[1009..1013] when)) (S (NP-SBJ-2 (NNS:[1014..1024] microsomes)) (VP (VBD:[1025..1029] were) (VP (VBN:[1030..1038] prepared) (NP-2 (-NONE-:[1038..1038] *)) (PP (IN:[1039..1043] from) (NP (NP (NNS:[1044..1050] livers)) (PP (IN:[1051..1053] of) (NP (JJ:[1054..1063] untreated) (NN:[1064..1066] B6) (NNS:[1068..1072] mice))))) (ADVP-TMP-1 (-NONE-:[1072..1072] *T*))))))) (.:[1072..1073] .))) ;sentence 7 Span:1074..1135 ;In every case MBAG was a better inhibitor than MGBG in vitro. ;[1088..1092]:substance:"MBAG" ;[1106..1115]:substance:"inhibitor" ;[1121..1125]:substance:"MGBG" (SENT (S (PP (IN:[1074..1076] In) (NP (DT:[1077..1082] every) (NN:[1083..1087] case))) (NP-SBJ (NN:[1088..1092] MBAG)) (VP (VBD:[1093..1096] was) (NP-PRD (NP (DT:[1097..1098] a) (JJR:[1099..1105] better) (NN:[1106..1115] inhibitor)) (PP (IN:[1116..1120] than) (NP (NN:[1121..1125] MGBG)))) (ADVP (FW:[1126..1128] in) (FW:[1129..1134] vitro))) (.:[1134..1135] .))) ;sentence 8 Span:1136..1303 ;The in vitro inhibition of MGBG of several drug metabolizing enzymes was not ;reversed when microsomes were preincubated with 1 mM putrescine, spermidine ;or spermine. ;[1164..1168]:substance:"MGBG" ;[1180..1205]:substance:"drug metabolizing enzymes" ;[1263..1264]:quantitative-value:"1" ;[1265..1267]:quantitative-units:"mM" ;[1268..1278]:substance:"putrescine" ;[1280..1290]:substance:"spermidine" ;[1294..1302]:substance:"spermine" (SENT (S (NP-SBJ-1 (NP (DT:[1136..1139] The) (ADJP (FW:[1140..1142] in) (FW:[1143..1148] vitro)) (NN:[1150..1160] inhibition)) (PP (IN:[1161..1163] of) (NP (NN:[1164..1168] MGBG))) (PP (IN:[1169..1171] of) (NP (JJ:[1172..1179] several) (ADJP (NN:[1180..1184] drug) (VBG:[1185..1197] metabolizing)) (NNS:[1198..1205] enzymes)))) (VP (VBD:[1206..1209] was) (RB:[1210..1213] not) (VP (VBN:[1214..1222] reversed) (NP-1 (-NONE-:[1222..1222] *)) (SBAR-ADV (WHADVP-2 (WRB:[1223..1227] when)) (S (NP-SBJ-3 (NNS:[1229..1239] microsomes)) (VP (VBD:[1240..1244] were) (VP (VBN:[1245..1257] preincubated) (NP-3 (-NONE-:[1257..1257] *)) (PP-MNR (IN:[1258..1262] with) (NP (NML (CD:[1263..1264] 1) (NN:[1265..1267] mM)) (NN:[1268..1278] putrescine) (,:[1278..1279] ,) (NN:[1280..1290] spermidine) (CC:[1291..1293] or) (NN:[1294..1302] spermine))) (ADVP-TMP-2 (-NONE-:[1302..1302] *T*)))))))) (.:[1302..1303] .))) ;sentence 9 Span:1304..1486 ;These results suggest that the anti-cancer drug, MGBG, has a severe ;effect(s) on the drug metabolizing system at concentrations reached during ;the treatment of patients with MGBG. ;[1336..1352]:substance:"anti-cancer drug" ;[1354..1358]:substance:"MGBG" ;[1391..1395]:substance:"drug" ;[1481..1485]:substance:"MGBG" (SENT (S (NP-SBJ (DT:[1304..1309] These) (NNS:[1311..1318] results)) (VP (VBP:[1319..1326] suggest) (SBAR (IN:[1327..1331] that) (S (NP-SBJ (NP (DT:[1332..1335] the) (NML (AFX:[1336..1340] anti) (HYPH:[1340..1341] -) (NN:[1341..1347] cancer)) (NN:[1348..1352] drug)) (,:[1352..1353] ,) (NP (NN:[1354..1358] MGBG))) (,:[1358..1359] ,) (VP (VBZ:[1360..1363] has) (NP (NP (DT:[1364..1365] a) (JJ:[1366..1372] severe) (NN:[1373..1382] effect-LRB-s-RRB-)) (PP (IN:[1383..1385] on) (NP (DT:[1386..1389] the) (ADJP (NN:[1391..1395] drug) (VBG:[1396..1408] metabolizing)) (NN:[1409..1415] system)))) (PP (IN:[1416..1418] at) (NP (NP (NNS:[1419..1433] concentrations)) (VP (VBN:[1434..1441] reached) (NP (-NONE-:[1441..1441] *)) (PP-TMP (IN:[1442..1448] during) (NP (NP (DT:[1449..1452] the) (NN:[1453..1462] treatment)) (PP (IN:[1463..1465] of) (NP (NNS:[1467..1475] patients))) (PP (IN:[1476..1480] with) (NP (NN:[1481..1485] MGBG)))))))))))) (.:[1485..1486] .))) ;section 10 Span:1490..1534 ;PMID: 3878657 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1490..1494] PMID) (::[1494..1495] :) (CD:[1496..1503] 3878657) (NN:[1504..1505] -LSB-) (NNP:[1505..1511] PubMed) (::[1512..1513] -) (NN:[1514..1521] indexed) (IN:[1522..1525] for) (NNP:[1526..1534] MEDLINE-RSB-)))