;PMID: 9242359 ;source_file_1872.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..38] = [t:0..38] ;1)sentence:[e:44..213] = [t:44..213] ;2)section:[e:217..254] = [t:217..254] ;3)section:[e:258..421] = [t:258..421] ;4)sentence:[e:425..544] = [t:425..544] ;5)sentence:[e:545..683] = [t:545..683] ;6)sentence:[e:684..838] = [t:684..838] ;7)sentence:[e:839..954] = [t:839..954] ;8)sentence:[e:955..1148] = [t:955..1148] ;9)sentence:[e:1149..1324] = [t:1149..1324] ;10)sentence:[e:1325..1459] = [t:1325..1459] ;11)sentence:[e:1460..1651] = [t:1460..1651] ;12)sentence:[e:1652..1885] = [t:1652..1885] ;13)sentence:[e:1886..2062] = [t:1886..2062] ;14)section:[e:2066..2110] = [t:2066..2110] ;section 0 Span:0..38 ;Toxicol Lett. 1997 Jun 16;92(1):67-77. (SEC (FRAG (NNP:[0..7] Toxicol) (NNP:[8..12] Lett) (.:[12..13] .) (CD:[14..18] 1997) (NNP:[19..22] Jun) (CD:[23..25] 16) (::[25..26] ;) (CD:[26..28] 92) (-LRB-:[28..29] -LRB-) (CD:[29..30] 1) (-RRB-:[30..31] -RRB-) (::[31..32] :) (CD:[32..34] 67) (::[34..35] -) (CD:[35..37] 77) (.:[37..38] .))) ;sentence 1 Span:44..213 ;alpha-Tocopheryl hemisuccinate administration increases rat liver subcellular ; alpha-tocopherol levels and protects against carbon tetrachloride-induced ;hepatotoxicity. ;[44..74]:substance:"alpha-Tocopheryl hemisuccinate" ;[123..139]:substance:"alpha-tocopherol" ;[168..188]:substance:"carbon tetrachloride" (SENT (S-HLN (NP-SBJ (NML (NN:[44..60] alpha-Tocopheryl) (NN:[61..74] hemisuccinate)) (NN:[75..89] administration)) (VP (VP (VBZ:[90..99] increases) (NP (NN:[100..103] rat) (NN:[104..109] liver) (JJ:[110..121] subcellular) (NN:[123..139] alpha-tocopherol) (NNS:[140..146] levels))) (CC:[147..150] and) (VP (VBZ:[151..159] protects) (PP-CLR (IN:[160..167] against) (NP (ADJP (NML (NN:[168..174] carbon) (NN:[175..188] tetrachloride)) (HYPH:[188..189] -) (VBN:[189..196] induced)) (NN:[198..212] hepatotoxicity))))) (.:[212..213] .))) ;section 2 Span:217..254 ;Tirmenstein MA, Leraas TL, Fariss MW. (SEC (FRAG (NNP:[217..228] Tirmenstein) (NNP:[229..231] MA) (,:[231..232] ,) (NNP:[233..239] Leraas) (NNP:[240..242] TL) (,:[242..243] ,) (NNP:[244..250] Fariss) (NNP:[251..253] MW) (.:[253..254] .))) ;section 3 Span:258..421 ;Department of Pharmaceutical Sciences, College of Pharmacy and Graduate ;Program in Pharmacology/Toxicology, Washington State University, Pullman ;99164-6510, USA. (SEC (FRAG (NNP:[258..268] Department) (IN:[269..271] of) (NNP:[272..286] Pharmaceutical) (NNP:[287..295] Sciences) (,:[295..296] ,) (NNP:[297..304] College) (IN:[305..307] of) (NNP:[308..316] Pharmacy) (CC:[317..320] and) (NNP:[321..329] Graduate) (NNP:[330..337] Program) (IN:[339..341] in) (NNP:[342..354] Pharmacology) (SYM:[354..355] /) (NNP:[355..365] Toxicology) (,:[365..366] ,) (NNP:[367..377] Washington) (NNP:[378..383] State) (NNP:[384..394] University) (,:[394..395] ,) (NNP:[396..403] Pullman) (CD:[404..409] 99164) (HYPH:[409..410] -) (CD:[410..414] 6510) (,:[414..415] ,) (NNP:[417..420] USA) (.:[420..421] .))) ;sentence 4 Span:425..544 ;Rats were administered a series of tocopherol analogs 18 h prior to a ;hepatotoxic dose of carbon tetrachloride (CCl4). ;[460..470]:substance:"tocopherol" ;[471..478]:substance:"analogs" ;[479..481]:quantitative-value:"18" ;[482..483]:quantitative-units:"h" ;[516..536]:substance:"carbon tetrachloride" ;[538..542]:substance:"CCl4" (SENT (S (NP-SBJ-1 (NNS:[425..429] Rats)) (VP (VBD:[430..434] were) (VP (VBN:[435..447] administered) (NP-1 (-NONE-:[447..447] *)) (NP (NP (DT:[448..449] a) (NN:[450..456] series)) (PP (IN:[457..459] of) (NP (NN:[460..470] tocopherol) (NNS:[471..478] analogs)))) (NP-TMP (NP (CD:[479..481] 18) (NN:[482..483] h)) (ADJP (JJ:[484..489] prior) (PP (TO:[490..492] to) (NP (NP (DT:[493..494] a) (JJ:[496..507] hepatotoxic) (NN:[508..512] dose)) (PP (IN:[513..515] of) (NP (NP (NN:[516..522] carbon) (NN:[523..536] tetrachloride)) (NP (-LRB-:[537..538] -LRB-) (NN:[538..542] CCl4) (-RRB-:[542..543] -RRB-)))))))))) (.:[543..544] .))) ;sentence 5 Span:545..683 ;Of the compounds tested, only d-alpha-tocopheryl hemisuccinate (TS) provided ;significant protection against CCl4-induced hepatotoxicity. ;[552..561]:substance:"compounds" ;[576..608]:substance:"d-alpha-tocopheryl hemisuccinate" ;[610..612]:substance:"TS" ;[655..659]:substance:"CCl4" (SENT (S (PP-TPC-1 (IN:[545..547] Of) (NP (NP (DT:[548..551] the) (NNS:[552..561] compounds)) (VP (VBN:[562..568] tested) (NP (-NONE-:[568..568] *))))) (,:[568..569] ,) (NP-SBJ (NP (NP (ADVP (RB:[570..574] only)) (NN:[576..594] d-alpha-tocopheryl) (NN:[595..608] hemisuccinate)) (NP (-LRB-:[609..610] -LRB-) (NN:[610..612] TS) (-RRB-:[612..613] -RRB-))) (PP-1 (-NONE-:[613..613] *T*))) (VP (VBD:[614..622] provided) (NP (NP (JJ:[623..634] significant) (NN:[635..645] protection)) (PP (IN:[646..653] against) (NP (ADJP (NN:[655..659] CCl4) (HYPH:[659..660] -) (VBN:[660..667] induced)) (NN:[668..682] hepatotoxicity))))) (.:[682..683] .))) ;sentence 6 Span:684..838 ;No protection was observed with either d-alpha-tocopherol (alpha-T) or a ;tocopherol succinate ether derivative, d-alpha-tocopheryloxybutyric acid ;(TSE). ;[724..742]:substance:"d-alpha-tocopherol" ;[744..751]:substance:"alpha-T" ;[758..795]:substance:"tocopherol succinate ether derivative" ;[798..831]:substance:"d-alpha-tocopheryloxybutyric acid" ;[833..836]:substance:"TSE" (SENT (S (NP-SBJ-1 (DT:[684..686] No) (NN:[687..697] protection)) (VP (VBD:[698..701] was) (VP (VBN:[702..710] observed) (NP-1 (-NONE-:[710..710] *)) (PP (IN:[711..715] with) (NP (CC:[716..722] either) (NP (NP (NN:[724..742] d-alpha-tocopherol)) (NP (-LRB-:[743..744] -LRB-) (NN:[744..751] alpha-T) (-RRB-:[751..752] -RRB-))) (CC:[753..755] or) (NP (NP (DT:[756..757] a) (NML (NN:[758..768] tocopherol) (NN:[769..778] succinate)) (NN:[779..784] ether) (NN:[785..795] derivative)) (,:[795..796] ,) (NP (NP (JJ:[798..826] d-alpha-tocopheryloxybutyric) (NN:[827..831] acid)) (NP (-LRB-:[832..833] -LRB-) (NN:[833..836] TSE) (-RRB-:[836..837] -RRB-)))))))) (.:[837..838] .))) ;sentence 7 Span:839..954 ;None of the tocopherol analogs significantly inhibited CYP2E1 activity as ;measured by oxidation of p-nitrophenol. ;[851..861]:substance:"tocopherol" ;[862..869]:substance:"analogs" ;[895..901]:cyp450:"CYP2E1" ;[940..953]:substance:"p-nitrophenol" (SENT (S (NP-SBJ (NP (NN:[839..843] None)) (PP (IN:[844..846] of) (NP (DT:[847..850] the) (NN:[851..861] tocopherol) (NNS:[862..869] analogs)))) (ADVP-EXT (RB:[871..884] significantly)) (VP (VBD:[885..894] inhibited) (NP (NN:[895..901] CYP2E1) (NN:[902..910] activity)) (PP-MNR (IN:[911..913] as) (S-NOM (NP-SBJ-1 (-NONE-:[913..913] *)) (VP (VBN:[914..922] measured) (NP-1 (-NONE-:[922..922] *)) (PP-MNR (IN:[923..925] by) (NP (NP (NN:[926..935] oxidation)) (PP (IN:[936..938] of) (NP (NN:[940..953] p-nitrophenol))))))))) (.:[953..954] .))) ;sentence 8 Span:955..1148 ;Liver homogenates and subcellular fractions (cytosol, nuclei, plasma ;membranes, mitochondria and microsomes) were collected 18 h after tocopherol ;analog administration in the absence of CCl4. ;[1080..1082]:quantitative-value:"18" ;[1083..1084]:quantitative-units:"h" ;[1092..1102]:substance:"tocopherol" ;[1103..1109]:substance:"analog" ;[1143..1147]:substance:"CCl4" (SENT (S (NP-SBJ-1 (NP (NN:[955..960] Liver) (NNS:[961..972] homogenates)) (CC:[973..976] and) (NP (JJ:[977..988] subcellular) (NNS:[989..998] fractions) (PRN (-LRB-:[999..1000] -LRB-) (NP (NP (NN:[1000..1007] cytosol)) (,:[1007..1008] ,) (NP (NNS:[1009..1015] nuclei)) (,:[1015..1016] ,) (NP (NN:[1018..1024] plasma) (NNS:[1025..1034] membranes)) (,:[1034..1035] ,) (NP (NNS:[1036..1048] mitochondria)) (CC:[1049..1052] and) (NP (NNS:[1053..1063] microsomes))) (-RRB-:[1063..1064] -RRB-)))) (VP (VBD:[1065..1069] were) (VP (VBN:[1070..1079] collected) (NP-1 (-NONE-:[1079..1079] *)) (PP (NP-ADV (CD:[1080..1082] 18) (NN:[1083..1084] h)) (IN:[1085..1090] after) (NP (NP (NN:[1092..1102] tocopherol) (NN:[1103..1109] analog) (NN:[1110..1124] administration)) (PP (IN:[1125..1127] in) (NP (NP (DT:[1128..1131] the) (NN:[1132..1139] absence)) (PP (IN:[1140..1142] of) (NP (NN:[1143..1147] CCl4))))))))) (.:[1147..1148] .))) ;sentence 9 Span:1149..1324 ;Homogenate and subcellular alpha-T levels were not significantly increased ;following TSE administration but were increased 2-3 fold following TS and ;alpha-T administration. ;[1177..1184]:substance:"alpha-T" ;[1235..1238]:substance:"TSE" ;[1274..1282]:quantitative-value:"2-3 fold" ;[1293..1295]:substance:"TS" ;[1300..1307]:substance:"alpha-T" (SENT (S (NP-SBJ-3 (NP (NN:[1149..1159] Homogenate) (NML-2 (-NONE-:[1159..1159] *P*))) (CC:[1160..1163] and) (NP (JJ:[1165..1176] subcellular) (NML-2 (NN:[1177..1184] alpha-T) (NNS:[1185..1191] levels)))) (VP (VP (VBD:[1192..1196] were) (RB:[1197..1200] not) (ADVP-EXT (RB:[1201..1214] significantly)) (VP (VBN:[1215..1224] increased) (NP-3 (-NONE-:[1224..1224] *)) (S-TMP (NP-SBJ (-NONE-:[1224..1224] *)) (VP (VBG:[1225..1234] following) (NP (NN:[1235..1238] TSE) (NN:[1240..1254] administration)))))) (CC:[1255..1258] but) (VP (VBD:[1259..1263] were) (VP (VBN:[1264..1273] increased) (NP-3 (-NONE-:[1273..1273] *)) (ADVP-EXT (QP (CD:[1274..1275] 2) (HYPH:[1275..1276] -) (CD:[1276..1277] 3)) (RB:[1278..1282] fold)) (S-TMP (NP-SBJ (-NONE-:[1282..1282] *)) (VP (VBG:[1283..1292] following) (NP (NP (NN:[1293..1295] TS) (NML-1 (-NONE-:[1295..1295] *P*))) (CC:[1296..1299] and) (NP (NN:[1300..1307] alpha-T) (NML-1 (NN:[1309..1323] administration))))))))) (.:[1323..1324] .))) ;sentence 10 Span:1325..1459 ;Total tocopherol levels (alpha-T+ TS + TSE) in liver homogenates and ;subcellular fractions were highest in rats supplemented with TS. ;[1331..1341]:substance:"tocopherol" ;[1350..1357]:substance:"alpha-T" ;[1359..1361]:substance:"TS" ;[1364..1367]:substance:"TSE" ;[1456..1458]:substance:"TS" (SENT (S (NP-SBJ (NP (JJ:[1325..1330] Total) (NN:[1331..1341] tocopherol) (NNS:[1342..1348] levels) (PRN (-LRB-:[1349..1350] -LRB-) (NP (NN:[1350..1357] alpha-T) (SYM:[1357..1358] +) (NN:[1359..1361] TS) (SYM:[1362..1363] +) (NN:[1364..1367] TSE)) (-RRB-:[1367..1368] -RRB-))) (PP-LOC (IN:[1369..1371] in) (NP (NP (NN:[1372..1377] liver) (NNS:[1378..1389] homogenates)) (CC:[1391..1394] and) (NP (JJ:[1395..1406] subcellular) (NNS:[1407..1416] fractions))))) (VP (VBD:[1417..1421] were) (ADJP-PRD (JJS:[1422..1429] highest)) (PP-LOC (IN:[1430..1432] in) (NP (NP (NNS:[1433..1437] rats)) (VP (VBN:[1438..1450] supplemented) (NP (-NONE-:[1450..1450] *)) (PP (IN:[1451..1455] with) (NP (NN:[1456..1458] TS))))))) (.:[1458..1459] .))) ;sentence 11 Span:1460..1651 ;In these animals, TS was detected in all subcellular fractions and total ;tocopherol levels were increased from 6-23 fold over those seen in controls ;and 2-9 fold over alpha-T treated rats. ;[1479..1481]:substance:"TS" ;[1534..1544]:substance:"tocopherol" ;[1573..1582]:quantitative-value:"6-23 fold" ;[1615..1623]:quantitative-value:"2-9 fold" ;[1630..1637]:substance:"alpha-T" (SENT (S (S (PP-LOC (IN:[1460..1462] In) (NP (DT:[1463..1468] these) (NNS:[1470..1477] animals))) (,:[1477..1478] ,) (NP-SBJ-2 (NN:[1479..1481] TS)) (VP (VBD:[1482..1485] was) (VP (VBN:[1486..1494] detected) (NP-2 (-NONE-:[1494..1494] *)) (PP-LOC (IN:[1495..1497] in) (NP (DT:[1498..1501] all) (JJ:[1502..1513] subcellular) (NNS:[1514..1523] fractions)))))) (CC:[1524..1527] and) (S (NP-SBJ-3 (JJ:[1528..1533] total) (NN:[1534..1544] tocopherol) (NNS:[1546..1552] levels)) (VP (VBD:[1553..1557] were) (VP (VBN:[1558..1567] increased) (NP-3 (-NONE-:[1567..1567] *)) (ADVP-EXT (ADVP (QP (IN:[1568..1572] from) (CD:[1573..1574] 6) (HYPH:[1574..1575] -) (CD:[1575..1577] 23)) (RB:[1578..1582] fold) (PP (IN:[1583..1587] over) (NP (NP (DT:[1588..1593] those)) (VP (VBN:[1594..1598] seen) (NP (-NONE-:[1598..1598] *)) (PP (IN:[1599..1601] in) (NP (NNS:[1602..1610] controls))))))) (CC:[1611..1614] and) (ADVP (QP (CD:[1615..1616] 2) (HYPH:[1616..1617] -) (CD:[1617..1618] 9)) (RB:[1619..1623] fold) (PP (IN:[1625..1629] over) (NP (ADJP (NN:[1630..1637] alpha-T) (VBN:[1638..1645] treated)) (NNS:[1646..1650] rats)))))))) (.:[1650..1651] .))) ;sentence 12 Span:1652..1885 ;In vitro studies in which liver homogenates and subcellular fractions were ;peroxidized with ascorbate and ADP/Fe suggest that increasing levels of ;alpha-T but not TS correlates with increased protection against lipid ;peroxidation. ;[1745..1754]:substance:"ascorbate" ;[1759..1762]:substance:"ADP" ;[1763..1765]:substance:"Fe" ;[1801..1808]:substance:"alpha-T" ;[1817..1819]:substance:"TS" ;[1866..1871]:substance:"lipid" (SENT (S (NP-SBJ (NP (ADJP (FW:[1652..1654] In) (FW:[1655..1660] vitro)) (NNS:[1661..1668] studies)) (SBAR (WHPP (IN:[1669..1671] in) (WHNP (WDT:[1672..1677] which))) (S (NP-SBJ-1 (NP (NN:[1678..1683] liver) (NNS:[1684..1695] homogenates)) (CC:[1696..1699] and) (NP (JJ:[1701..1712] subcellular) (NNS:[1713..1722] fractions))) (VP (VBD:[1723..1727] were) (VP (VBN:[1728..1739] peroxidized) (NP-1 (-NONE-:[1739..1739] *)) (PP-MNR (IN:[1740..1744] with) (NP (NP (NN:[1745..1754] ascorbate)) (CC:[1755..1758] and) (NP (NN:[1759..1762] ADP) (SYM:[1762..1763] /) (NN:[1763..1765] Fe))))))))) (VP (VBP:[1766..1773] suggest) (SBAR (IN:[1774..1778] that) (S (NP-SBJ (NP (VBG:[1780..1790] increasing) (NNS:[1791..1797] levels)) (PP (IN:[1798..1800] of) (NP (NP (NN:[1801..1808] alpha-T)) (CONJP (CC:[1809..1812] but) (RB:[1813..1816] not)) (NP (NN:[1817..1819] TS))))) (VP (VBZ:[1820..1830] correlates) (PP-CLR (IN:[1831..1835] with) (NP (NP (VBN:[1836..1845] increased) (NN:[1846..1856] protection)) (PP (IN:[1858..1865] against) (NP (NN:[1866..1871] lipid) (NN:[1872..1884] peroxidation))))))))) (.:[1884..1885] .))) ;sentence 13 Span:1886..2062 ;These results suggest that the ability of TS to protect against CCl4-induced ;hepatotoxicity relates to its enhanced hepatic accumulation and subsequent ;hydrolysis to alpha-T. ;[1928..1930]:substance:"TS" ;[1951..1955]:substance:"CCl4" ;[2054..2061]:substance:"alpha-T" (SENT (S (NP-SBJ (DT:[1886..1891] These) (NNS:[1892..1899] results)) (VP (VBP:[1900..1907] suggest) (SBAR (IN:[1908..1912] that) (S (NP-SBJ (NP (DT:[1913..1916] the) (NN:[1917..1924] ability) (S-1 (-NONE-:[1924..1924] *ICH*))) (PP (IN:[1925..1927] of) (NP (NN:[1928..1930] TS))) (S-1 (NP-SBJ (-NONE-:[1930..1930] *)) (VP (TO:[1931..1933] to) (VP (VB:[1935..1942] protect) (PP-CLR (IN:[1943..1950] against) (NP (ADJP (NN:[1951..1955] CCl4) (HYPH:[1955..1956] -) (VBN:[1956..1963] induced)) (NN:[1964..1978] hepatotoxicity))))))) (VP (VBZ:[1979..1986] relates) (PP-CLR (TO:[1987..1989] to) (NP (NP (PRP$:[1990..1993] its) (VBN:[1994..2002] enhanced) (JJ:[2003..2010] hepatic) (NN:[2012..2024] accumulation)) (CC:[2025..2028] and) (NP (NP (JJ:[2029..2039] subsequent) (NN:[2040..2050] hydrolysis)) (PP (TO:[2051..2053] to) (NP (NN:[2054..2061] alpha-T)))))))))) (.:[2061..2062] .))) ;section 14 Span:2066..2110 ;PMID: 9242359 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2066..2070] PMID) (::[2070..2071] :) (CD:[2072..2079] 9242359) (NN:[2080..2081] -LSB-) (NNP:[2081..2087] PubMed) (::[2088..2089] -) (NN:[2090..2097] indexed) (IN:[2098..2101] for) (NNP:[2102..2109] MEDLINE) (-RRB-:[2109..2110] -RSB-)))