title: Hepatoprotective effects of polymethoxyflavones against acute and chronic carbon tetrachloride intoxication.
abstract: In the present study, we explore the protective effects of Citrus aurantium L. extract (CAE) against acute and chronic CCl4-induced hepatotoxicity. The quantitative analysis of CAE was performed using HPLC-UV to determine the nobiletin content was approximately 27%. For the acute model, the male ICR mice were orally treated with water, silymarin (positive control, 200 mg/kg) and CAE (50 and 200 mg/kg) for 3 days prior to CCl4 (1 mL/kg, 50% v/v in olive oil) IP injection. For the chronic model (n = 6/group), the mice were treated with each treatment for 28 consecutive days and CCl4 (1 mL/kg, 20%) was injected twice a week. In both the acute and chronic models, the CCl4 alone treated group showed histopathologic alterations with a significantly increase in serum hepatic enzyme levels together with a disrupted anti-oxidative status. In contrast, the CAE treatments restored pathologic alterations and recovered the oxidative status by enhancing antioxidant enzymes and reducing lipid peroxidation levels. Furthermore, CAE enhanced nuclear factor E2-related factor 2 (Nrf2) and its related cytoprotective signals, including NAD(P)H quinone oxidoreductase 1, UDP-glucuronosyltransferase, and γ-glutamylcysteine synthetase. Taken together, the present study demonstrates that CAE exerts a protective effect against CCl4-induced hepatotoxicity with its anti-oxidant, anti-inflammatory, and anti-apoptotic activity.
authors.affiliation: College of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Yusung-gu, Daejeon, 305-764, South Korea.
authors.forename: Tae-Won
authors.initials: TW
authors.lastname: Kim
authors.affiliation: NutraPham Tech, Yongin, Gyeonggi, 449-728, South Korea.
authors.forename: Dong-Ryung
authors.initials: DR
authors.lastname: Lee
authors.affiliation: NutraPham Tech, Yongin, Gyeonggi, 449-728, South Korea.
authors.forename: Bong-Keun
authors.initials: BK
authors.lastname: Choi
authors.affiliation: College of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Yusung-gu, Daejeon, 305-764, South Korea.
authors.forename: Hwan-Kyu
authors.initials: HK
authors.lastname: Kang
authors.affiliation: College of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Yusung-gu, Daejeon, 305-764, South Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Graduate School of Biomedicine & Health Sciences, Catholic University, Seocho-gu, Seoul, 06591, South Korea.
authors.forename: Seol-Wa
authors.initials: SW
authors.lastname: Lim
authors.affiliation: Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, 449-728, South Korea. Electronic address: ymichigan@mju.ac.kr.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi, 449-728, South Korea. Electronic address: jwsuh@mju.ac.kr.
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Suh
mesh_terms: D000208:Acute Disease; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000517:prevention & control*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D002908:Chronic Disease; D047309:Flavones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
chemical_list: D047309:Flavones
keywords: Acute model; Carbon tetrachloride (CCl(4)); Chronic model; Citrus aurantium extract (CAE); Liver damage