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These changes lead to cell injury, and chronic liver injury leads to excessive deposition of collagen in liver, resulting in liver fibrosis. The aim of this study was to evaluate the effects of long-term Salvia miltiorrhiza administration in CCl4-induced hepatic injury in rats. Salvia miltiorrhiza (10, 25 or 50 mg kg\u22121 twice a day) was given for 9 weeks, beginning at the same time as the injections of CCl4. Rats receiving CCl4 alone showed a decreased hepatic glutathione level and an increased glutathione-S-transferase content. The hepatic thiobarbituratic acid-reactive substance levels were increased. CCl4 also caused a prominent collagen deposition in liver histology that was further supported by the increased hepatic mRNA expression of transforming growth factor-\u03b21, tissue inhibitor of metallproteinase-1 and procollagen I. Salvia miltiorrhiza administration led to a dose-dependent increase in hepatic glutathione levels and a decrease in peroxidation products. Additionally, it reduced the mRNA expression of markers for hepatic fibrogenesis. In conclusion, long-term administration of Salvia miltiorrhiza in rats ameliorated the CCl4-induced hepatic injury that probably related to a reduced oxidant stress and degree of hepatic fibrosis.<\/jats:p>","DOI":"10.1211\/0022357022098","type":"journal-article","created":{"date-parts":[[2003,12,1]],"date-time":"2003-12-01T23:48:55Z","timestamp":1070322535000},"page":"1561-1568","source":"Crossref","is-referenced-by-count":40,"title":["Long-term administration of <i>Salvia miltiorrhiza<\/i> ameliorates carbon tetrachloride-induced hepatic fibrosis in rats"],"prefix":"10.1093","volume":"55","author":[{"given":"Tzung-Yan","family":"Lee","sequence":"first","affiliation":[{"name":"Institute of Traditional Medicine, National Yang-Ming University School of Medicine , Taipei,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guei-Jane","family":"Wang","sequence":"additional","affiliation":[{"name":"National Research Institute of Chinese Medicine , Taipei,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jen-Hwey","family":"Chiu","sequence":"additional","affiliation":[{"name":"Institute of Traditional Medicine, National Yang-Ming University School of Medicine , Taipei,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine , Taipei,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2003,11,1]]},"reference":[{"key":"2024103109400623100_cit1","first-page":"876","article-title":"Pharmacology of Salvia miltiorrhiza","volume":"19","author":"Chen","year":"1993","journal-title":"Acta Pharm. Sin."},{"key":"2024103109400623100_cit2","first-page":"443","article-title":"Reaction of glutathione with a free radical metabolite of carbon tetrachloride","volume":"37","author":"Connor","year":"1990","journal-title":"Mol. Pharmacol."},{"key":"2024103109400623100_cit3","doi-asserted-by":"crossref","first-page":"33881","DOI":"10.1074\/jbc.274.48.33881","article-title":"Glutathione levels discriminate between oxidative stress and transforming growth factor-beta signaling in activated rat hepatic stellate cells","volume":"274","author":"De Bleser","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2024103109400623100_cit4","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1006\/taap.1993.1072","article-title":"Vitamin A potentiation of carbon tetrachloride hepatotoxicity: role of liver macrophages and active oxygen species","volume":"119","author":"ElSisi","year":"1993","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"2024103109400623100_cit5","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0891-5849(88)90023-8","article-title":"Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: characterization and comparison with homogenates and microsomes","volume":"4","author":"Fraga","year":"1988","journal-title":"Free Radic. Biol. Med."},{"key":"2024103109400623100_cit6","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":"2024103109400623100_cit7","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1053\/jhep.2000.20243","article-title":"Mechanisms and therapy of hepatic fibrosis: report of the AASLD Single Topic Basic Research Conference","volume":"32","author":"Friedman","year":"2000","journal-title":"Hepatology"},{"key":"2024103109400623100_cit8","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":"2024103109400623100_cit9","first-page":"1647","article-title":"Tissue inhibitor of metalloproteinase-1 and \u22122 RNA expression in rat and human liver fibrosis","volume":"150","author":"Herbst","year":"1997","journal-title":"Am. J. Pathol."},{"key":"2024103109400623100_cit10","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1248\/bpb.24.1271","article-title":"The protective effects of PMC against chronic carbon tetrachloride-induced hepatotoxicity in vivo","volume":"24","author":"Hsiao","year":"2001","journal-title":"Biol. Pharm. Bull."},{"key":"2024103109400623100_cit11","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1139\/y01-029","article-title":"Hemodynamic effects of Salvia miltiorrhiza on cirrhotic rats","volume":"79","author":"Huang","year":"2001","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"2024103109400623100_cit12","first-page":"176","article-title":"Tissue inhibitor of metalloproteinase-1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis","volume":"24","author":"Iredale","year":"1996","journal-title":"Hepatology"},{"key":"2024103109400623100_cit13","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1021\/bi00406a019","article-title":"Ethanol-, fasting-, and acetone-inducible cytochromes P-450 in rat liver: regulation and characteristics of enzymes belonging to the IIB and IIE gene subfamilies","volume":"27","author":"Johansson","year":"1988","journal-title":"Biochemistry"},{"key":"2024103109400623100_cit14","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev.pa.25.040185.003435","article-title":"The regulation of hepatic glutathione","volume":"25","author":"Kaplowitz","year":"1985","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"2024103109400623100_cit15","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":"2024103109400623100_cit16","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1351\/pac199870030547","article-title":"Biologically active components from traditional Chinese medicines","volume":"70","author":"Li","year":"1998","journal-title":"Pure Appl. Chem."},{"key":"2024103109400623100_cit17","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0006-2952(92)90271-J","article-title":"Protective action of seven natural phenolic compounds against peroxidative damage to biomembranes","volume":"43","author":"Liu","year":"1992","journal-title":"Biochem. 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Dis."},{"key":"2024103109400623100_cit26","first-page":"51","article-title":"Enhanced lipid peroxidation in hepatic cirrhosis","volume":"46","author":"Pratico","year":"1998","journal-title":"J. Invest. Med."},{"key":"2024103109400623100_cit27","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0163-7258(89)90050-8","article-title":"Mechanisms of carbon tetrachloride toxicity","volume":"43","author":"Recknagel","year":"1989","journal-title":"Pharmacol. 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