{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:47:50Z","timestamp":1791186470326,"version":"4.1.0"},"reference-count":42,"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":4079,"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":[[2004,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Our previous study demonstrated that polycationic liposomes are highly stable in the bloodstream and represent an effective agent for liver gene delivery. We report here that liposome-mediated extracellular superoxide dismutase (EC-SOD) gene delivery successfully prevented acute liver injury in mice. The therapeutic efficacy of EC-SOD gene delivery by polycationic liposomes was determined against the toxicity of superoxide anions and hydroxyethyl radicals in HepG2 cells and in a mouse model of acute liver injury caused by D-galactosamine and lipopolysaccharide intoxication. Transfection of HepG2 cells with an EC-SOD plasmid led to a striking increase in superoxide dismutase activity in the medium. The transfected cells had much less cell death after reactive oxygen species exposure compared with untransfected or control plasmid-transfected cells. In a model of acute liver injury, serum alanine aminotransferase levels in mice receiving portal vein injections of EC-SOD lipoplexes were much lower than in those receiving normal saline, liposomes alone, or control lipoplexes. Liver histology confirmed that there was less cell death in the EC-SOD lipoplex-treated group. Quantitative reverse transcriptase polymerase chain reaction showed a 55-fold increase in human EC-SOD gene expression in the liver of mice injected with EC-SOD lipoplexes. Serum superoxide dismutase activity in EC-SOD lipoplex-treated mice was higher than in the control groups; this was associated with higher liver glutathione levels and reduced lipid peroxidation. <jats:underline>In conclusion<\/jats:underline>, polycationic liposome-mediated EC-SOD gene delivery protects against reactive oxygen species toxicity <jats:italic toggle=\"yes\">in vitro<\/jats:italic> and against lipopolysaccharide-induced acute liver injury in D-galactosamine-sensitized mice. (Hepatology 2004;40:195-204.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.20288","type":"journal-article","created":{"date-parts":[[2004,7,2]],"date-time":"2004-07-02T07:03:11Z","timestamp":1088751791000},"page":"195-204","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":49,"title":["Liposome-mediated extracellular superoxide dismutase gene delivery protects against acute liver injury in mice\u2020"],"prefix":"10.1097","volume":"40","author":[{"given":"Jian","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy D.","family":"Yen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Catana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Nantz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Zern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-29-20241201","doi-asserted-by":"crossref","first-page":"585607","DOI":"10.1517\/13543784.8.5.585","article-title":"Toxicity of hepatotoxins: new insights into mechanisms and therapy.","volume":"8","author":"Wu","year":"1999","journal-title":"Exp Opin Invest Drugs"},{"key":"R2-29-20241201","doi-asserted-by":"crossref","first-page":"665672","DOI":"10.1007\/s005350070045","article-title":"Hepatic stellate cells, a target for the treatment of liver fibrosis.","volume":"35","author":"Wu","year":"2000","journal-title":"J Gastroenterol"},{"key":"R3-29-20241201","first-page":"359365","article-title":"Protective effect of S-adenosyl-L-methionine on bromobenzene- or D-galactosamine toxicity to isolated rat hepatocytes.","volume":"23","author":"Wu","year":"1996","journal-title":"HEPATOLOGY"},{"key":"R4-29-20241201","doi-asserted-by":"crossref","first-page":"669677","DOI":"10.1016\/S0168-8278(97)80434-5","article-title":"Effects of vitamin E, ascorbic acid and catalase on bromobenzene- and hydrogen peroxide-induced intracellular oxidation and single strand DNA breakage in Hep G2 cells.","volume":"26","author":"Wu","year":"1997","journal-title":"J Hepatol"},{"key":"R5-29-20241201","doi-asserted-by":"crossref","first-page":"772778","DOI":"10.1002\/hep.510270319","article-title":"Increased liver up-take of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents.","volume":"27","author":"Wu","year":"1998","journal-title":"HEPATOLOGY"},{"key":"R6-29-20241201","doi-asserted-by":"crossref","first-page":"397405","DOI":"10.1053\/jhep.2001.22002","article-title":"Mechanism of cell death during warm hepatic ischemic-reperfusion in rats: apoptosis or necrosis.","volume":"33","author":"Gujral","year":"2001","journal-title":"HEPATOLOGY"},{"key":"R7-29-20241201","first-page":"7480","article-title":"Extracellular superoxide dismutase.","volume":"349","author":"Marklund","year":"2002","journal-title":"Methods Enzymol"},{"key":"R8-29-20241201","doi-asserted-by":"crossref","first-page":"13981403","DOI":"10.1172\/JCI111550","article-title":"Extracellular superoxide dismutase in human tissues and human cell lines.","volume":"74","author":"Marklund","year":"1984","journal-title":"J Clin Invest"},{"key":"R9-29-20241201","doi-asserted-by":"crossref","first-page":"14861491","DOI":"10.1172\/JCI113230","article-title":"Human red cells scavenge extracellular hydrogen peroxide and inhibit formation of hypochlorous acid and hydroxyl radical.","volume":"80","author":"Winterbourn","year":"1987","journal-title":"J Clin Invest"},{"key":"R10-29-20241201","first-page":"G476G484","article-title":"Inhibition of carbon tetrachloride-induced liver injury by liposomes containing vitamin E.","volume":"267","author":"Yao","year":"1994","journal-title":"Am J Physiol"},{"key":"R11-29-20241201","doi-asserted-by":"crossref","first-page":"11731180","DOI":"10.1053\/jhep.2001.24267","article-title":"Detoxification of reactive oxygen species by a nonpeptidyl mimic of superoxide dismutase cures acetaminophen-induced acute liver failure in the mouse.","volume":"33","author":"Ferret","year":"2001","journal-title":"HEPATOLOGY"},{"key":"R12-29-20241201","doi-asserted-by":"crossref","first-page":"14511459","DOI":"10.1053\/gast.2001.29590","article-title":"The superoxide dismutase mimetic MnTBAP prevents Fas-induced acute liver failure in the mouse.","volume":"121","author":"Malassagne","year":"2001","journal-title":"Gastroenterology"},{"key":"R13-29-20241201","doi-asserted-by":"crossref","first-page":"12411250","DOI":"10.1053\/gast.2001.23253","article-title":"Delivery of the CuZn-superoxide dismutase gene with adenovirus reduces early alcohol-induced liver injury in rats.","volume":"120","author":"Wheeler","year":"2001","journal-title":"Gastroenterology"},{"key":"R14-29-20241201","doi-asserted-by":"crossref","first-page":"18931898","DOI":"10.1161\/01.CIR.103.14.1893","article-title":"Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction.","volume":"103","author":"Li","year":"2001","journal-title":"Circulation"},{"key":"R15-29-20241201","doi-asserted-by":"crossref","first-page":"21672177","DOI":"10.1089\/10430340152710513","article-title":"Comparison of the effect of adenoviral delivery of three superoxide dismutase genes against hepatic ischemia-reperfusion injury.","volume":"12","author":"Wheeler","year":"2001","journal-title":"Human Gene Ther"},{"key":"R16-29-20241201","doi-asserted-by":"crossref","first-page":"17951817","DOI":"10.1517\/13543784.7.11.1795","article-title":"The prospects of hepatic drug delivery and gene therapy.","volume":"7","author":"Wu","year":"1998","journal-title":"Exp Opin Invest Drugs"},{"key":"R17-29-20241201","doi-asserted-by":"crossref","first-page":"16471652","DOI":"10.1038\/sj.gt.3301923","article-title":"Gene therapy progress and prospects: nonviral vectors.","volume":"9","author":"Niidome","year":"2002","journal-title":"Gene Ther"},{"key":"R18-29-20241201","doi-asserted-by":"crossref","first-page":"647652","DOI":"10.1038\/nbt0797-647","article-title":"Improved DNA:liposome complexes for increased systemic delivery and gene expression.","volume":"15","author":"Templeton","year":"1997","journal-title":"Nature Biotechnol"},{"key":"R19-29-20241201","doi-asserted-by":"crossref","first-page":"205212","DOI":"10.1007\/s001090000185","article-title":"Asialofetuin liposome-mediated human 1-antitrypsin gene transfer in vivo results in stationary long-term gene expression.","volume":"79","author":"Dasi","year":"2001","journal-title":"J Mol Med"},{"key":"R20-29-20241201","doi-asserted-by":"crossref","first-page":"517523","DOI":"10.1038\/sj.gt.3300424","article-title":"Factors controlling the efficiency of cationic lipid-mediated transfection in vivo via intravenous administration.","volume":"4","author":"Liu","year":"1997","journal-title":"Gene Ther"},{"key":"R21-29-20241201","first-page":"d717d725","article-title":"Targeting hepatocytes for drug and gene delivery: emerging novel approaches and applications.","volume":"7","author":"Wu","year":"2002","journal-title":"Front Biosci"},{"key":"R22-29-20241201","doi-asserted-by":"crossref","first-page":"1034910354","DOI":"10.1073\/pnas.96.18.10349","article-title":"Correction of the UDP-glucuronosyltransferase gene defect in the Gunn rat model of Crigler-Najjar syndrome type I with chimeric oligonucleotide.","volume":"96","author":"Kren","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R23-29-20241201","doi-asserted-by":"crossref","first-page":"799809","DOI":"10.1089\/104303401750148748","article-title":"Cationic liposome-mediated gene delivery to the liver and to hepatocellular carcinoma in mice.","volume":"12","author":"Mohr","year":"2001","journal-title":"Hum Gene Ther"},{"key":"R24-29-20241201","doi-asserted-by":"crossref","first-page":"306313","DOI":"10.1023\/A:1007501122611","article-title":"In vivo gene delivery to the liver using novel galactosylated cationic liposomes.","volume":"17","author":"Kawakami","year":"2000","journal-title":"Pharm Res"},{"key":"R25-29-20241201","doi-asserted-by":"crossref","first-page":"251257","DOI":"10.1021\/bc000097e","article-title":"Cationic lipid polymerization as a novel approach for constructing new DNA delivery agents.","volume":"12","author":"Wu","year":"2001","journal-title":"Bioconjugate Chem"},{"key":"R26-29-20241201","doi-asserted-by":"crossref","first-page":"180187","DOI":"10.1038\/sj.gt.3301861","article-title":"Poly(cationic lipid)-mediated in vivo gene delivery to mouse liver.","volume":"10","author":"Liu","year":"2003","journal-title":"Gene Ther"},{"key":"R27-29-20241201","doi-asserted-by":"crossref","first-page":"63406344","DOI":"10.1073\/pnas.84.18.6340","article-title":"Isolation and sequence of complementary DNA encoding human extracellular superoxide dismutase.","volume":"84","author":"Hjalmarsson","year":"1987","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R28-29-20241201","doi-asserted-by":"crossref","first-page":"614627","DOI":"10.1016\/S0168-8278(98)80157-8","article-title":"Superoxide-induced changes in endothelin receptors in hepatic stellate cells.","volume":"29","author":"Gabriel","year":"1998","journal-title":"J Hepatol"},{"key":"R30-29-20241201","doi-asserted-by":"crossref","first-page":"432444","DOI":"10.1053\/gast.2003.50064","article-title":"Telomerase reconstitution immortalizes human fetal hepatocytes without disrupting their differentiation potential.","volume":"124","author":"Wege","year":"2003","journal-title":"Gastroenterology"},{"key":"R31-29-20241201","doi-asserted-by":"crossref","first-page":"619628","DOI":"10.1111\/j.1530-0277.2001.tb02259.x","article-title":"Removal of glutathione produces apoptosis and necrosis in Hep G2 cells overexpressing CYP2E1.","volume":"25","author":"Wu","year":"2001","journal-title":"Alcohol Clin Exp Res"},{"key":"R33-29-20241201","doi-asserted-by":"crossref","first-page":"166176","DOI":"10.1093\/toxsci\/65.2.166","article-title":"Mechanisms of hepatoxicity.","volume":"65","author":"Jaeschke","year":"2002","journal-title":"Toxicol Sci"},{"key":"R34-29-20241201","doi-asserted-by":"crossref","first-page":"15391543","DOI":"10.1016\/S0891-5849(01)00743-2","article-title":"CYP2E1-dependent toxicity and oxidative stress in Hep G2 cells.","volume":"31","author":"Cederbaum","year":"2001","journal-title":"Free Rad Biol Med"},{"key":"R35-29-20241201","first-page":"337350","article-title":"Successful treatment of primary and disseminated human lung cancers by systemic delivery of tumor suppressor genes using an improved liposome vector.","volume":"4","author":"Ramesh","year":"2001","journal-title":"Mol Ther"},{"key":"R36-29-20241201","doi-asserted-by":"crossref","first-page":"85378541","DOI":"10.1016\/S0021-9258(18)81824-5","article-title":"Interactions between human extracellular superoxide dismutase C and sulfated polysaccharides.","volume":"264","author":"Adachi","year":"1989","journal-title":"J Biol Chem"},{"key":"R37-29-20241201","doi-asserted-by":"crossref","first-page":"14411450","DOI":"10.1053\/jhep.2001.24561","article-title":"Etoposide prevents apoptosis in mouse liver with D-galactosamine lipopolysaccharide-induced fulminant hepatic failure resulting in reduction of lethality.","volume":"33","author":"Nakama","year":"2001","journal-title":"HEPATOLOGY"},{"key":"R38-29-20241201","doi-asserted-by":"crossref","first-page":"3139","DOI":"10.1124\/jpet.102.043539","article-title":"Neurokinin-1 receptor antagonists CP-96,345 and L-733,060 protect mice from cytokine-mediated liver injury.","volume":"305","author":"Bang","year":"2003","journal-title":"J Pharmacol Exp Ther"},{"key":"R39-29-20241201","doi-asserted-by":"crossref","first-page":"197208","DOI":"10.1172\/JCI16010","article-title":"Defective TNF--mediated hepatocellular apoptosis and liver damage in acidic sphingomyelinase knockout mice.","volume":"111","author":"Garcia-Ruiz","year":"2003","journal-title":"J Clin Invest"},{"key":"R40-29-20241201","doi-asserted-by":"crossref","first-page":"550558","DOI":"10.1038\/sj.gt.3301916","article-title":"Amelioration of antigen-induced arthritis in rats by transfer of extracellular superoxide dismutase and catalase genes.","volume":"10","author":"Dai","year":"2003","journal-title":"Gene Ther"},{"key":"R41-29-20241201","doi-asserted-by":"crossref","first-page":"321325","DOI":"10.1002\/jgm.194","article-title":"EC-SOD gene therapy reduces paracetamol induced liver damage in mice.","volume":"3","author":"Laukkanen","year":"2001","journal-title":"J Gene Med"},{"key":"R42-29-20241201","doi-asserted-by":"crossref","first-page":"685606","DOI":"10.1089\/104303401300057405","article-title":"Contribution of plasmid DNA to hepatotoxicity after systemic administration of lipoplexes.","volume":"12","author":"Loisel","year":"2001","journal-title":"Hum Gene Ther"},{"key":"R43-29-20241201","doi-asserted-by":"crossref","first-page":"731738","DOI":"10.1006\/mthe.2002.0598","article-title":"CpG-depleted plasmid DNA vectors with enhanced safety and long-term gene expression in vivo.","volume":"5","author":"Yew","year":"2002","journal-title":"Mol Ther"},{"key":"R44-29-20241201","doi-asserted-by":"crossref","first-page":"935940","DOI":"10.1038\/sj.gt.3302036","article-title":"Molecular basis of the inflammatory response to adenovirus vectors.","volume":"10","author":"Liu","year":"2003","journal-title":"Gene Ther"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.20288","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200407000-00029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T12:01:01Z","timestamp":1733054461000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200407000-00029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,7]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.20288","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2004,7]]}}}