Analysis of the molecular mechanism of hepatic GSH decrease during drug induced liver injury.

药物性肝损伤过程中肝脏GSH降低的分子机制分析

• 批准号: 22790146
• 负责人: ITO Kousei
• 金额: $ 2.58万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790146/
• 关键词: 医療・福祉; 薬剤反応性; 薬剤性肝障害; トランスポーター

It is known that pretreatment of minimum amount of lipopolysaccharide(LPS) increases the animals to drug-induced liver injury, otherwise they are hardly affected by drug alone. In addition to previously proposed inflammatory cytokines produced by LPS pre-treatment, we have demonstrated that hepatic GSH decrease is an important factor cooperatively aggravates DILI in this LPS model. Moreover, species difference of the mechanism of hepatic GSH decrease after LPS treatment was emerged ; basolateral efflux of GSH was increased in rat, while metabolic pathway was somehow involved in mouse.

已知最少量的脂多糖（LPS）预处理增加动物对药物诱导的肝损伤，否则它们几乎不受单独药物的影响。除了先前提出的由LPS预处理产生的炎性细胞因子之外，我们已经证明了肝脏GSH减少是在该LPS模型中协同加重DILI的重要因素。此外，LPS处理后GSH减少的机制存在种属差异，大鼠GSH的基底外侧外排增加，而小鼠GSH的外排可能与代谢途径有关。

项目成果

Sustained intrahepatic glutathione depletion causes proteasomal degradation of multidrug esistance-associated protein 2 in rat liver

持续的肝内谷胱甘肽消耗导致大鼠肝脏中多药耐药相关蛋白 2 的蛋白酶体降解

• 期刊: Biochim Biophys Acta
• 作者: Sekine S;Mitsuki K;Ito K;Kugioka S and Horie T
• 通讯作者: Kugioka S and Horie T

Hepatic glutathione and inflammatory cytokines cooperatively regulateonset of drug-induced liver injury.

肝脏谷胱甘肽和炎症细胞因子协同调节药物引起的肝损伤的发生。

• 发表时间: 2010
• 作者: Ikebuchi Y;Ito K;Honma M;Kozawa M;Yamamoto T;Suzuki H.
• 通讯作者: Suzuki H.

Hepatic glutathione decrease and inflammatory cytokines are key factors in lipopolysaccharide pre-administered drug-induced liver injury model

肝脏谷胱甘肽减少和炎症细胞因子是脂多糖预给药药物性肝损伤模型的关键因素

• 发表时间: 2012
• 作者: Ito K;Ikebuchi Y;Honma M;Kozawa M;Yamamoto T and Suzuki H
• 通讯作者: Yamamoto T and Suzuki H

Itraconazole-induced cholestasis : involvement of the inhibition of bile canalicular phospholipid translocator MDR3/ABCB4

伊曲康唑诱导的胆汁淤积：涉及胆小管磷脂易位蛋白 MDR3/ABCB4 的抑制

• DOI: 10.1124/mol.110.067256
• 发表时间: 2011
• 期刊: Mol Pharmacol
• 影响因子: 3.6
• 作者: T.Yoshikado;T.Takada;T.Yamamoto;H.Yamaji;K.Ito;T.Santa;H.Yokota;Y.Yatomi;H.Yoshida;J.Goto;S.Tsuji;H.Suzuki
• 通讯作者: H.Suzuki

Post-translational regulation of ABC transporters involved in bile flow formation.

参与胆汁流形成的 ABC 转运蛋白的翻译后调节。

• 发表时间: 2011
• 作者: 伊藤晃成;関根秀一;堀江利治;鈴木洋史
• 通讯作者: 鈴木洋史