{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:11:58Z","timestamp":1790885518040,"version":"4.1.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4595,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,2]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The liver-selective nitric oxide (NO) donor, <jats:italic toggle=\"yes\">O<\/jats:italic>\n                                 <jats:sup>2<\/jats:sup>-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO\/NO), is metabolized by P-450 enzymes to release NO in the liver, and is shown to protect the liver from tumor necrosis factor \u03b1 (TNF-\u03b1)-induced apoptosis and D-glactosamine\/endotoxin-induced hepatotoxicity. This study was undertaken to examine the effects of V-PYRRO\/NO on acetaminophen-induced hepatotoxicity in mice. Mice were given V-PYRRO\/NO via osmotic pumps (1.8-5.4 mg\/mL, 8 \u03bcL\/h) 4 to 16 hours before a hepatotoxic dose of acetaminophen (600 mg\/kg, intraperitoneally [ip]). V-PYRRO\/NO administration dramatically reduced acetaminophen-induced hepatotoxicity in a dose- and time-dependent manner, as evidenced by reduced serum alanine aminotransferase (ALT) activity, reduced hepatic congestion, apoptosis, and improved hepatocellular pathology. The protection afforded by V-PYRRO\/NO does not appear to be caused by a decrease in the formation of toxic acetaminophen metabolites, which consumes glutathione (GSH), because V-PYRRO\/NO did not alter acetaminophen-induced hepatic GSH depletion. Acetaminophen-induced lipid peroxidation, as determined by the concentrations of 4-hydroxyalkenals (4-HNE) and malondialdehyde (MDA), was reduced significantly by V-PYRRO\/NO treatment. Although pretreatment was most effective, administration of V-PYRRO\/NO simultaneously with acetaminophen also was able to reduce acetaminophen hepatotoxicity. Genomic analysis of the liver samples 10 hours after acetaminophen intoxication showed the enhanced expression of genes associated with stress\/oxidative stress, apoptosis\/cell death, and DNA damage\/repair. Acetaminophen-induced alterations in gene expression were attenuated significantly by V-PYRRO\/NO. Real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western-blot analysis confirmed microarray results. In conclusion, V-PYRRO\/NO is effective in blocking acetaminophen-induced hepatotoxicity in mice. This protection may involve the reduction of oxidative stress, the inhibition of apoptosis, and possibly the maintenance of hepatic vasculature to prevent congestion.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2003.50063","type":"journal-article","created":{"date-parts":[[2003,2,5]],"date-time":"2003-02-05T02:43:33Z","timestamp":1044413013000},"page":"324-333","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":79,"title":["The nitric oxide donor, V-PYRRO\/NO, protects against acetaminophen-induced hepatotoxicity in mice"],"prefix":"10.1097","volume":"37","author":[{"given":"Jie","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxiu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Waalkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Page","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Saavedra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry K.","family":"Keefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1053\/jhep.2003.50063-BIB1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1146\/annurev.me.35.020184.003045","volume":"35","author":"Black","year":"1984","journal-title":"Annu Rev Med"},{"key":"10.1053\/jhep.2003.50063-BIB2","first-page":"159","volume-title":"Toxicology of the Liver","author":"Cohen","year":"1998","unstructured":", . Acetaminophen-induced hepatotoxicity. In: , eds. Toxicology of the Liver. 2nd ed. Washington: Taylor & Francis, 1998;159-186."},{"key":"10.1053\/jhep.2003.50063-BIB3","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1073\/pnas.81.5.1327","volume":"81","author":"Dahlin","year":"1984","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1053\/jhep.2003.50063-BIB4","first-page":"195","volume":"187","author":"Jollow","year":"1973","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1053\/jhep.2003.50063-BIB5","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3109\/03602539509029816","volume":"27","author":"Hinson","year":"1995","journal-title":"Drug Metab Rev"},{"key":"10.1053\/jhep.2003.50063-BIB6","first-page":"2493","volume":"45","author":"Mason","year":"1986","journal-title":"Fed Proc"},{"key":"10.1053\/jhep.2003.50063-BIB7","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1093\/toxsci\/62.2.212","volume":"62","author":"Knight","year":"2001","journal-title":"Toxicol Sci"},{"key":"10.1053\/jhep.2003.50063-BIB8","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1006\/niox.2001.0385","volume":"5","author":"Michael","year":"2001","journal-title":"Nitric Oxide"},{"key":"10.1053\/jhep.2003.50063-BIB9","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/sj.bjp.0704500","volume":"135","author":"Fiorucci","year":"2002","journal-title":"Br J Pharmacol"},{"key":"10.1053\/jhep.2003.50063-BIB10","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/sj.bjp.0703837","volume":"132","author":"Futter","year":"2001","journal-title":"Br J Pharmacol"},{"key":"10.1053\/jhep.2003.50063-BIB11","first-page":"2732","volume":"7","author":"Keefer","year":"2000","journal-title":"Pharm News"},{"key":"10.1053\/jhep.2003.50063-BIB12","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1021\/jm9701031","volume":"40","author":"Saavedra","year":"1997","journal-title":"J Med Chem"},{"key":"10.1053\/jhep.2003.50063-BIB13","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1080\/00498250110102665","volume":"32","author":"Stinson","year":"2002","journal-title":"Xenobiotica"},{"key":"10.1053\/jhep.2003.50063-BIB14","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/00007890-200101270-00004","volume":"71","author":"Ricciardi","year":"2001","journal-title":"Transplantation"},{"key":"10.1053\/jhep.2003.50063-BIB15","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1124\/jpet.300.1.18","volume":"300","author":"Liu","year":"2002","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1053\/jhep.2003.50063-BIB16","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1053\/jhep.2000.18291","volume":"32","author":"Kim","year":"2000","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50063-BIB17","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1006\/niox.1997.0136","volume":"1","author":"Ou","year":"1997","journal-title":"Nitric Oxide"},{"key":"10.1053\/jhep.2003.50063-BIB18","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/hep.510300135","volume":"30","author":"Deleve","year":"1999","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50063-BIB19","first-page":"94","volume":"32","author":"Moal","year":"2000","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50063-BIB20","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1002\/hep.510270316","volume":"27","author":"Gardner","year":"1998","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50063-BIB21","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1021\/tx9800349","volume":"11","author":"Hinson","year":"1998","journal-title":"Chem Res Toxicol"},{"key":"10.1053\/jhep.2003.50063-BIB22","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1002\/hep.510340230","volume":"34","author":"Kim","year":"2000","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50063-BIB23","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1089\/152308601300185214","volume":"3","author":"Laskin","year":"2001","journal-title":"Antioxid Redox Signal"},{"key":"10.1053\/jhep.2003.50063-BIB24","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1053\/jhep.2002.30956","volume":"35","author":"Bourdi","year":"2002","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50063-BIB25","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1006\/niox.2001.0404","volume":"6","author":"Hinson","year":"2002","journal-title":"Nitric Oxide"},{"key":"10.1053\/jhep.2003.50063-BIB26","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/0003-2697(69)90064-5","volume":"27","author":"Tietze","year":"1969","journal-title":"Anal Biochem"},{"key":"10.1053\/jhep.2003.50063-BIB27","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/jbt.8","volume":"15","author":"Walker","year":"2001","journal-title":"J Biochem Mol Toxicol"},{"key":"10.1053\/jhep.2003.50063-BIB28","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/hep.1840050213","volume":"5","author":"Walker","year":"1985","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50063-BIB29","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/toxsci\/65.1.135","volume":"65","author":"Ruepp","year":"2002","journal-title":"Toxicol Sci"},{"key":"10.1053\/jhep.2003.50063-BIB30","doi-asserted-by":"crossref","first-page":"147","DOI":"10.3109\/03602539509029821","volume":"27","author":"Nelson","year":"1995","journal-title":"Drug Metab Rev"},{"key":"10.1053\/jhep.2003.50063-BIB31","first-page":"580","volume":"289","author":"Liu","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1053\/jhep.2003.50063-BIB32","first-page":"415","volume":"9","author":"Dimmeler","year":"1998","journal-title":"Cell Growth Differ"},{"key":"10.1053\/jhep.2003.50063-BIB33","first-page":"138","volume":"47","author":"Blazka","year":"1996","journal-title":"J Inflamm"},{"key":"10.1053\/jhep.2003.50063-BIB34","first-page":"259","volume":"92","author":"Blazka","year":"1996","journal-title":"Res Commun Mol Pathol Pharmacol"},{"key":"10.1053\/jhep.2003.50063-BIB35","first-page":"179","volume":"19","author":"Buzard","year":"2000","journal-title":"J Environ Pathol Toxicol Oncol"},{"key":"10.1053\/jhep.2003.50063-BIB36","first-page":"1470","volume":"279","author":"Ray","year":"1996","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1053\/jhep.2003.50063-BIB37","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1053\/jhep.2002.35058","volume":"36","author":"Yagnik","year":"2002","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2003.50063-BIB38","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/S0006-2952(97)00048-8","volume":"53","author":"DeLeve","year":"1997","journal-title":"Biochem Pharmacol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/01515467-200302000-00014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T11:33:28Z","timestamp":1733052808000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200302000-00014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,2]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2003]]}},"URL":"https:\/\/doi.org\/10.1053\/jhep.2003.50063","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2003,2]]}}}