{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:29:15Z","timestamp":1790911755062,"version":"4.1.0"},"reference-count":45,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:p> A protective effect of Rho-kinase inhibitor on various organ injuries is gaining attention. Regarding liver injury, Rho-kinase inhibitor is reported to prevent carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)- or dimethylnitrosamine-induced liver fibrosis and hepatic ischemia-reperfusion injury in rats. Because Rho-kinase inhibitor not only improved liver fibrosis but also reduced serum alanine aminotransferase (ALT) level in CCl<jats:sub>4<\/jats:sub>-induced liver fibrosis, we wondered whether Rho-kinase inhibitor might exert a direct hepatocyte-protective effect. We examined this possibility in acute CCl<jats:sub>4<\/jats:sub> intoxication in rats. Rho-kinase inhibitor, HA-1077, reduced serum alanine ALT level in rats with acute liver injury induced by CCl<jats:sub>4<\/jats:sub> with the improvement of histological damage and the reduction of the number of apoptotic cells. In cultured rat hepatocytes in serum-free condition, HA-1077 reduced apoptosis evaluated by quantitative determination of cytoplasmic histone-associated DNA oligonucleosome fragments with the reduction of caspase-3 activity and the enhancement of Bcl-2 expression. HA-1077 stimulated phosphorylation of Akt, and wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-kinase)\/Akt pathway, abrogated the reduction of hepatocyte apoptosis by HA-1077 in vitro. Furthermore, wortmannin abrogated the reduction of serum ALT level by HA-1077 in rats with acute liver injury induced by CCl<jats:sub>4<\/jats:sub>, suggesting that the activation of PI3-kinase\/Akt pathway may be involved in the hepatocyte-protective effect by Rho-kinase inhibitor in vivo. In conclusion, Rho-kinase inhibitor prevented hepatocyte damage in acute liver injury induced by CCl<jats:sub>4<\/jats:sub> in rats and merits consideration as a hepatocyte-protective agent in liver injury, considering its direct antiapoptotic effect on hepatocytes in vitro. <\/jats:p>","DOI":"10.1152\/ajpgi.00210.2007","type":"journal-article","created":{"date-parts":[[2007,8,30]],"date-time":"2007-08-30T21:09:32Z","timestamp":1188508172000},"page":"G911-G917","source":"Crossref","is-referenced-by-count":32,"title":["Rho-kinase inhibitor prevents hepatocyte damage in acute liver injury induced by carbon tetrachloride in rats"],"prefix":"10.1152","volume":"293","author":[{"given":"Hitoshi","family":"Ikeda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Kume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Tejima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Tomiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Nishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuko","family":"Ohtomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Omata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Yatomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000111804.34509.94"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a134609"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2003.12.004"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1038\/35070009"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4274(98)00110-6"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5300.661"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711580211"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a134130"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-4804(02)00081-1"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00039.2003"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2003.50049"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00107-5"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1823"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.04.023"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-06-0045"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5272.245"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.10.5313"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201253200"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.140.3.627"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000052593.16876.AF"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-4804(03)00202-6"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(01)00169-6"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.278.1.C57"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(84)90769-9"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00945-8"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10081"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1128"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1038\/35070019"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(73)90357-1"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20602"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65594-0"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.2.284"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1992.76.4.0571"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200211000-00013"},{"key":"R35","doi-asserted-by":"crossref","unstructured":"Shiotani S, Shimada M, Suehiro T, Soejima Y, Yosizumi T, Shimokawa H, Maehara Y. Involvement of Rho-kinase in cold ischemia-reperfusion injury after liver transplantation in rats. Transplantation 78: 375\u2013382, 2004.","DOI":"10.1097\/01.TP.0000128618.41619.E7"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2003.09.001"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-5877-0_65"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005121375"},{"key":"R39","doi-asserted-by":"crossref","unstructured":"Tada S, Iwamoto H, Nakamuta M, Sugimoto R, Enjoji M, Nakashima Y, Nawata H. A selective ROCK inhibitor, Y27632, prevents dimethylnitrosamine-induced hepatic fibrosis in rats. J Hepatol 34: 529\u2013536, 2001.","DOI":"10.1016\/S0168-8278(00)00059-3"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1067\/msy.2003.59"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.20677"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0705406"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000163544.17221.BE"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000142813.33538.82"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3634"}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.00210.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T22:15:57Z","timestamp":1567980957000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.00210.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,10]]},"references-count":45,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2007,10]]}},"alternative-id":["10.1152\/ajpgi.00210.2007"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00210.2007","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,10]]}}}