{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:15:55Z","timestamp":1789946155495,"version":"4.0.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2003,8,1]],"date-time":"2003-08-01T00:00:00Z","timestamp":1059696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Quercetin, one of the most abundant flavonoids in human diet has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the protective effect of quercetin on hepatic injury induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN caused a significant decrease in body and liver weight. Oral administration of quercetin (10 mg kg\u22121 daily for 4 weeks) remarkably prevented this DMN-induced loss in body and liver weight and inhibited the elevation of serum alanine transaminase, aspartate transaminase and bilirubin levels. Quercetin also increased serum albumin and hepatic glutathione levels and reduced the hepatic level of malondialdehyde. Furthermore, DMN-induced elevation of hydroxyproline content was reduced in the quercetin treated rats, the result of which was consistent with a reduction in type I collagen mRNA production and histological analysis of liver tissue stained with Sirius red. A reduction in hepatic stellate cell activation, as assessed by \u03b1-smooth muscle actin staining, was associated with quercetin treatment as well as a reduction in transforming growth factor-\u03b21 expression. In conclusion, these results demonstrate that quercetin exhibited in-vivo hepatoprotective and anti-fibrogenic effects against DMN-induced liver injury and suggest that quercetin may be useful in the preventing the development of hepatic fibrosis.<\/jats:p>","DOI":"10.1211\/0022357021396","type":"journal-article","created":{"date-parts":[[2003,9,2]],"date-time":"2003-09-02T23:55:06Z","timestamp":1062546906000},"page":"1169-1174","source":"Crossref","is-referenced-by-count":74,"title":["The flavonoid quercetin inhibits dimethylnitrosamine-induced liver damage in rats"],"prefix":"10.1093","volume":"55","author":[{"given":"Eun-Sil","family":"Lee","sequence":"first","affiliation":[{"name":"College of Pharmacy, Pusan National University , Kumjeong-gu, Pusan 609\u2013735,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Pusan National University , Kumjeong-gu, Pusan 609\u2013735,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Young","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, Pusan National University , Seo-Gu, Pusan 602\u2013739,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sik","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, Pusan National University , Seo-Gu, Pusan 602\u2013739,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeon-Ok","family":"Moon","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Pusan National University , Kumjeong-gu, Pusan 609\u2013735,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,8,1]]},"reference":[{"key":"2024103109394465100_cit1","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/S0076-6879(78)52032-6","article-title":"Microsomal lipid peroxidation","volume":"12","author":"Buege","year":"1978","journal-title":"Methods. Enzymol."},{"key":"2024103109394465100_cit2","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1056\/NEJM199104043241401","article-title":"Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy","volume":"324","author":"Castilla","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"2024103109394465100_cit3","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1074\/jbc.275.4.2247","article-title":"Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury","volume":"275","author":"Friedman","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2024103109394465100_cit4","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0168-8278(96)80074-2","article-title":"Effects of S-adenosylmethionine on lipid peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis","volume":"25","author":"Gasso","year":"1996","journal-title":"J. Hepatol."},{"key":"2024103109394465100_cit5","doi-asserted-by":"crossref","first-page":"12719","DOI":"10.1073\/pnas.96.22.12719","article-title":"In vivo inhibition of rat stellate cell activation by soluble transforming growth factor beta type II receptor: a potential new therapy for hepatic fibrosis","volume":"96","author":"George","year":"1999","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2024103109394465100_cit6","first-page":"S39","article-title":"Transdifferentiation of hepatic stellate cells (Ito cells) to myofibroblasts: a key event in hepatic fibrogenesis","volume":"49","author":"Gressner","year":"1996","journal-title":"Kidney Int."},{"key":"2024103109394465100_cit7","first-page":"1370","article-title":"Critical review on the determination of glutathione in biological preparations","volume":"33","author":"Higashi","year":"1988","journal-title":"Prot. Nucleic Enz."},{"key":"2024103109394465100_cit8","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/0168-8278(89)90160-8","article-title":"Dimethylnitrosamine-induced cirrhosis. Evidence for an immunological mechanism","volume":"8","author":"Jezequel","year":"1989","journal-title":"J. Hepatol."},{"key":"2024103109394465100_cit9","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/BF01002772","article-title":"Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections","volume":"11","author":"Junqueira","year":"1979","journal-title":"Histochem. J."},{"key":"2024103109394465100_cit10","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/S0891-5849(00)00198-2","article-title":"Biomarkers of oxidative stress study: are plasma antioxidants markers of CCl4 poisoning?","volume":"28","author":"Kadiiska","year":"2000","journal-title":"Free Rad. Biol. Med."},{"key":"2024103109394465100_cit11","first-page":"793","article-title":"Effect of genistein and quercetin on proliferation, collagen synthesis, and type I procollagen mRNA levels of rat hepatic stellate cells","volume":"22","author":"Kang","year":"2001","journal-title":"Acta Pharmacol. Sin."},{"key":"2024103109394465100_cit12","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1002\/hep.510270512","article-title":"Effect of antioxidants, resveratrol, quercetin, and N-acetylcysteine, on the functions of cultured rat hepatic stellate cells and Kupffer cells","volume":"27","author":"Kawada","year":"1998","journal-title":"Hepatology"},{"key":"2024103109394465100_cit13","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/ajcn\/76.3.560","article-title":"Flavonoid intake and risk of chronic diseases","volume":"76","author":"Knekt","year":"2002","journal-title":"Am. J. Clin. Nutr."},{"key":"2024103109394465100_cit14","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1172\/JCI118304","article-title":"Activation of hepatic stellate cells by TGF alpha and collagen IIS mediated by oxidative stress through c-myc expression","volume":"96","author":"Lee","year":"1995","journal-title":"J. Clin. Invest."},{"key":"2024103109394465100_cit15","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1046\/j.1440-1746.1999.01928.x","article-title":"Liver fibrogenesis and the role of hepatic stellate cells: new insights and prospects for therapy","volume":"14","author":"Li","year":"1999","journal-title":"J. Gastroenterol. Hepatol."},{"key":"2024103109394465100_cit16","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"2024103109394465100_cit17","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1111\/j.1530-0277.1999.tb04203.x","article-title":"Leukocytes as modulators of stellate cell activation","volume":"23","author":"Maher","year":"1999","journal-title":"Alcohol Clin. Exp. Res."},{"key":"2024103109394465100_cit18","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1006\/bbrc.1993.1927","article-title":"Stimulation of lipid peroxidation or 4-hydroxynonenal treatment increases procollagen alpha 1 (I) gene expression in human liver fat-storing cells","volume":"194","author":"Parola","year":"1993","journal-title":"Biochem. Biophys. Res. Comm."},{"key":"2024103109394465100_cit19","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/S0168-8278(00)80305-0","article-title":"The flavonoid quercetin ameliorates liver damage in rats with biliary obstruction","volume":"33","author":"Peres","year":"2000","journal-title":"J. Hepatol."},{"key":"2024103109394465100_cit20","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/ajcp\/28.1.56","article-title":"Colorimetric method for the determination of serum glutamic oxaloacetic acid and glutamic pyruvic transaminases","volume":"38","author":"Reitman","year":"1957","journal-title":"Am. Clin. Pathol."},{"key":"2024103109394465100_cit21","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1111\/j.1440-1746.1995.tb01798.x","article-title":"Role of oxidative stress in activation of Kupffer and Ito cells in liver fibrogenesis","volume":"10","author":"Tsukamoto","year":"1995","journal-title":"J. Gastroenterol. Hepatol."},{"key":"2024103109394465100_cit22","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1006\/taap.2001.9234","article-title":"Increased oxidative stress in dimethylnitrosamine-induced liver fibrosis in the rat: effect of N-acetylcysteine and interferon-\u03b1","volume":"175","author":"Vendemiale","year":"2001","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"2024103109394465100_cit23","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/0003-9861(61)90291-0","article-title":"The determination of hydroxyproline in tissue and protein samples containing small proportions of this amino acid","volume":"93","author":"Woessner","year":"1961","journal-title":"Arch. Biochem. Biophys."},{"key":"2024103109394465100_cit24","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/S0891-5849(00)00396-8","article-title":"The roles played by crucial free radicals like lipid free radicals, nitric oxide, and enzymes NOS and NADPH in CCl4-induced acute liver injury of mice","volume":"29","author":"Zhu","year":"2000","journal-title":"Free Rad. Biol. Med."}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1211%2F0022357021396","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/55\/8\/1169\/60259775\/0022357021396.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/55\/8\/1169\/60259775\/0022357021396.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T10:12:22Z","timestamp":1730369542000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/55\/8\/1169\/6150344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,8,1]]},"references-count":24,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2003,8,1]]},"published-print":{"date-parts":[[2003,8,1]]}},"URL":"https:\/\/doi.org\/10.1211\/0022357021396","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,8]]},"published":{"date-parts":[[2003,8,1]]}}}