{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:12:21Z","timestamp":1790475141147,"version":"4.1.0"},"reference-count":35,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    Acute liver failure (ALF) is a fatal syndrome attributed to massive hepatocyte death. Hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) has been reported to exert cytoprotective or cytotoxic effects. Here, we examined the role of cystathionine \u03b3-lyase (CSE, an enzyme produces H\n                    <jats:sub>2<\/jats:sub>\n                    S) in ALF induced by D-Galactosamine (GalN) and lipopolysaccharide (LPS).\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    Wild-type (WT) mice exhibited high mortality rate, prominent liver injury, and increased plasma alanine aminotransferase levels after GalN\/LPS challenge. Congenital deficiency or chemical inhibition of CSE by DL-propargylglycine attenuated GalN\/LPS-induced liver injury. CSE deficiency markedly improved survival rate and attenuated GalN\/LPS-induced upregulation of inflammatory cytokines and activation of caspase 3 and poly (ADP-ribose) polymerase (PARP) in the liver. CSE deficiency protected primary hepatocytes from GalN\/tumor necrosis factor-\u03b1 (TNF-\u03b1)-induced cell death without affecting LPS-induced TNF-\u03b1 production from primary peritoneal macrophages. Beneficial effects of CSE deficiency were associated with markedly elevated homocysteine and thiosulfate levels, upregulation of NF-E2 p45-related factor 2 (Nrf2) and antioxidant proteins, activation of Akt-dependent anti-apoptotic signaling, and inhibition of GalN\/LPS-induced JNK phosphorylation in the liver. Finally, administration of sodium thiosulfate (STS) attenuated GalN\/LPS-induced liver injury\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    activation of Akt- and Nrf2-dependent signaling and inhibition of GalN\/LPS-induced JNK phosphorylation in WT mice.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    These results suggest that inhibition of CSE or administration of STS prevents acute inflammatory liver failure by augmenting thiosulfate levels and upregulating antioxidant and anti-apoptotic defense in the liver.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    <\/jats:bold>\n                    Congenital deficiency or chemical inhibition of CSE increases thiosulfate levels in the liver and prevents ALF at least in part by augmentation of antioxidant and anti-apoptotic mechanisms.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal<\/jats:italic>\n                    . 20, 204\u2013216.\n                  <\/jats:p>","DOI":"10.1089\/ars.2013.5354","type":"journal-article","created":{"date-parts":[[2013,6,12]],"date-time":"2013-06-12T23:14:33Z","timestamp":1371078873000},"page":"204-216","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":86,"title":["Cystathionine \u03b3-Lyase Deficiency Protects Mice from Galactosamine\/Lipopolysaccharide-Induced Acute Liver Failure"],"prefix":"10.1177","volume":"20","author":[{"given":"Kazuhiro","family":"Shirozu","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Tokuda","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eizo","family":"Marutani","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lefer","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine","place":["Georgia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Lakehead University","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumito","family":"Ichinose","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,1,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181c0df00"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-009-1112-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.10080"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2012.01.015"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.11.5939"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2010.06.005"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4944"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2008.12.008"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi300778t"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3671"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.01.031"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21475"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199312163292508"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.180976"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201106-1152OC"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.01.038"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.374124"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.312694"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3391"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2613.2000.00144.x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00417.x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(73)90357-1"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.01.025"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.7.3100"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.9.3671"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199112000-00008"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.04.001"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4363"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.15.3086"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2011"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2011.02.004"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00704.x"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.02.033"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1162667"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-008-0407-2"}],"container-title":["Antioxidants &amp; 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