{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:55:56Z","timestamp":1772996156109,"version":"3.50.1"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":6636,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Glycine has been shown to prevent hepatocyte death induced by anoxia and by several toxic agents. However, the mechanisms responsible for such a cytoprotective effect have not yet been entirely clarified. We have previously shown that an uncontrolled increase in intracellular Na<jats:sup>+<\/jats:sup> is critical for hepatocyte killing induced by adenosine triphosphate (ATP) depletion. We herein report that protection by glycine (2 mmol\/L) against cytotoxicity induced in isolated rat hepatocyte by potassium cyanide (KCN) or hypoxia was associated with the prevention of cytosolic Na<jats:sup>+<\/jats:sup> accumulation. The addition of the Na<jats:sup>+<\/jats:sup> ionophore, monensin, abolished the effects of glycine on both Na<jats:sup>+<\/jats:sup> increase and cytotoxicity. Pretreating hepatocytes with the glycine- receptor antagonist, strychnine (1 mmol\/L), similarly prevented Na<jats:sup>+<\/jats:sup> overload and cell killing. Glycine at high concentrations and strychnine are known to block Cl<jats:sup>\u2212<\/jats:sup> channels in many cell types. Consistently, we have observed that glycine and strychnine prevented the increase of intracellular Cl<jats:sup>\u2212<\/jats:sup>levels caused by hypoxia or KCN. Incubation of hepatocytes in a Cl<jats:sup>\u2212<\/jats:sup>-free medium, obtained by substituting chloride with membrane-impermeable gluconate, significantly reduced Na<jats:sup>+<\/jats:sup> accumulation and cell killing triggered by hypoxia or KCN. Both these effects were abolished by the addition of monensin. The cytoprotective action exerted by hepatocyte incubation in the Cl(<jats:sup>\u2212<\/jats:sup>)-free medium was, however, lost when membrane-permeable nitrate, which allowed Na<jats:sup>+<\/jats:sup> accumulation, was used instead to replace chloride. Altogether, these results indicate that glycine inhibition of Cl<jats:sup>\u2212<\/jats:sup> conductance protects against hepatocyte killing induced by KCN and hypoxia by interfering with intracellular Na<jats:sup>+<\/jats:sup> accumulation triggered by ATP depletion.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510260114","type":"journal-article","created":{"date-parts":[[2004,7,27]],"date-time":"2004-07-27T23:15:44Z","timestamp":1090970144000},"page":"107-112","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":55,"title":["Glycine protects against hepatocyte killing by KCN or hypoxia by preventing intracellular Na+ overload in the rat"],"prefix":"10.1097","volume":"26","author":[{"given":"R","family":"Carini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Bellomo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"De Cesaris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Albano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.510260114","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-199707000-00015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T15:27:47Z","timestamp":1738942067000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-199707000-00015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,7]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1997]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.510260114","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[1997,7]]}}}