Branched-chain amino acids and L-carnitine attenuate lipotoxic hepatocellular damage in rat cirrhotic liver

• Material Type: 博士論文
• Title: Branched-chain amino acids and L-carnitine attenuate lipotoxic hepatocellular damage in rat cirrhotic liver
• Author/Editor: Tamai, Yasuyuki
• Author Heading: Tamai, Yasuyuki
• Publication, Distribution, etc.: 三重大学
• Publication Date: 2021-07-21
• Publication Date (W3CDTF): 2021-07-21
• Degree grantor/type: 三重大学
• Date Granted: 2021-07-21
• Date Granted (W3CDTF): 2021-07-21
• Dissertation Number: 甲医学第2080号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲医学第2080号
• Text Language Code: eng
• Alias of Author: タマイ, ヤスユキ; 玉井, 康将
• Subject Heading: L-carnitine; Branched-chain amino acids; Cirrhosis; Lipid peroxides; Cardiolipins
• Target Audience: 一般
• Note (General): application/pdf; Branched-chain amino acids (BCAA) reverse malnutrition and L-carnitine leads to the reduction of hyperammonemia and muscle cramps in cirrhotic patients. BCAA and L-carnitine are involved in glucose and fatty acid metabolism, however their mechanistic activity in cirrhotic liver is not fully understood. We aim to define the molecular mechanism(s) and combined effects of BCAA and L-carnitine using a cirrhotic rat model. Rats were administered carbon tetrachloride for 10 weeks to induce cirrhosis. During the last 6 weeks of administration, cirrhotic rats received BCAA, L-carnitine or a combination of BCAA and L-carnitine daily via gavage. We found that BCAA and L-carnitine treatments significantly improved hepatocellular function associated with reduced triglyceride level, lipid deposition and adipophilin expression, in cirrhotic liver. Lipidomic analysis revealed dynamic changes in hepatic lipid composition by BCAA and L-carnitine administrations. BCAA and L-carnitine globally increased molecular species of phosphatidylcholine. Liver triacylglycerol and phosphatidylcholine hydroperoxides were significantly decreased by BCAA and L-carnitine. Furthermore, serum and liver ATP levels were significantly increased in all treatments, which were attributed to the elevation of mature cardiolipins and mitochondrial component gene expressions. Finally, BCAA and L-carnitine dramatically reduced hepatocellular death. In conclusion, BCAA and L-carnitine treatments attenuate hepatocellular damage through the reduction of lipid peroxides and the overall maintenance of mitochondrial integrity within the cirrhotic liver. These effectiveness of BCAA and L-carnitine support the therapeutic strategies in human chronic liver diseases.; 本文/Department of Gastroenterology and Hepatology, Graduate School of Medicine, Mie University, Tsu, Japan; 11p
• DOI: info:doi/10.1016/j.biopha.2020.111181; https://doi.org/info:doi/10.1016/j.biopha.2020.111181
• Persistent ID (NDL): info:ndljp/pid/11929577; https://dl.ndl.go.jp/pid/11929577
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2021-12-07T08:33:55+09:00
• Date Created (W3CDTF): 2021-11-16
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10076/00020017; https://mie-u.repo.nii.ac.jp/records/14399
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp