丝裂霉素(MitoQ)是一种泛醌衍生的抗氧化剂
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Mitoquinone (MitoQ) is a ubiquinone-derived antioxidant that can covalently attach to a lipophilic triphenylphosphonium (TPP) cation, specifically targets mitochondria.[1] MitoQ is usually stored within mitochondria in vivo in order to prevent and protect the cellular damage induced by mitochondrial ROS overproduction and oxidative stress.[2]
In vitro experiment it shown that washed platelets incubated with MitoQ 10 μM (4.8% ± 0.8%) markedly increased calcein-negative population (cytotoxic effect) compared to a non-treated control group; MitoQ 10 μM (8.5% ± 2.2%) induced a significant increase in PS exposure on the platelet membrane when compared to the basal control.[3] In addition, MitoQ (5 μM) inhibited collagen and ADP-induced platelet aggregation in PRP samples. In the meanwhile, MitoQ at 2.5 and 5 μM produced a obvious decrease in ROS production generated by antimycin A or collagen on platelet.[3]
In vivo, treatment with 2.5 mg/kg and 5 mg/kg MitoQ can alleviate mouse lung histologic changes induced by CS (Cigarette smoke).[1] In vivo experiment it shown that mitoquinone treatment with 10 mg/kg/day by gavage after 4 weeks, liver structure obiviously improved in association with a significant decrease in collagen deposition. In the meanwhile, mitoquinone treatment determined a significant reduction in hepatic inflammation and fibrosis. Moreover, TIMP-1, MMP-2, and MMP-13 gene expressions were decreased by Mitoquinone treatment.[4]
参考文献:
[1]. Yang D, et al. Mitoquinone ameliorates cigarette smoke-induced airway inflammation and mucus hypersecretion in mice. Int Immunopharmacol. 2021 Jan;90:107149.
[2]. Chen W, et al. Inhibition of Mitochondrial ROS by MitoQ Alleviates White Matter Injury and Improves Outcomes after Intracerebral Haemorrhage in Mice. Oxid Med Cell Longev. 2020 Jan 4;2020:8285065.
[3]. Méndez D, et al. Mitoquinone (MitoQ) Inhibits Platelet Activation Steps by Reducing ROS Levels. Int J Mol Sci. 2020 Aug 27;21(17):6192.
[4]. Turkseven S, et al. Mitochondria-targeted antioxidant mitoquinone attenuates liver inflammation and fibrosis in cirrhotic rats. Am J Physiol Gastrointest Liver Physiol. 2020 Feb 1;318(2):G298-G304.
Mitoquinone (MitoQ) 是一种泛醌衍生的抗氧化剂,可以共价连接到亲脂性三苯基膦 (TPP) 阳离子上,专门针对线粒体。[1]MitoQ 通常储存在体内线粒体中,以便预防和保护由线粒体 ROS 过量产生和氧化应激引起的细胞损伤。[2]
体外实验表明,与未处理的对照组相比,用 MitoQ 10 μM (4.8% ± 0.8%) 孵育的洗涤过的血小板显着增加了钙黄绿素阴性群体(细胞毒性作用);与基础对照相比,MitoQ 10 μM (8.5% ± 2.2%) 可显着增加血小板膜上的 PS 暴露。[3] 此外,MitoQ (5 μM) 可抑制胶原蛋白和 ADP -在 PRP 样品中诱导血小板聚集。同时,2.5 和 5 μM 的 MitoQ 显着降低抗霉素 A 或血小板上胶原蛋白产生的 ROS。[3]
在体内,用 2.5 mg/kg 和 5 mg/kg MitoQ 处理可以减轻 CS(香烟烟雾)引起的小鼠肺组织学变化。[1] 体内实验表明,mitoquinone 处理4 周后以 10 mg/kg/天的剂量灌胃,肝脏结构明显改善,胶原蛋白沉积显着减少。同时,线粒体醌治疗可显着减少肝脏炎症和纤维化。此外,丝裂醌处理降低了 TIMP-1、MMP-2 和 MMP-13 基因的表达。[4]
Cell experiment [1]: | |
Cell lines |
Mouse Embryonic Fibroblasts (MEF) |
Preparation Method |
Cells were treated with MitoQ for 16 h. Superoxide anion was determined by incubating the cells with 50 nM MitoSox for 30 min. To analyze the effect of MitoQ 0.05 and 0.1 μM on acute oxidative stress, MEFwt cells were incubated with MitoSox in the absence or presence of 5 μM antimycin A. |
Reaction Conditions |
0.05 and 0.1 μM, 16h |
Applications |
MitoQ at 2.5 and 5 μM produced a significant decrease in ROS production generated by antimycin A or collagen on platelets. |
Animal experiment [2]: | |
Male Sprague-Dawley rats |
C57BL/10ScSn DMD mdx mice |
Preparation Method |
Mitoquinone (10 mg?kg?1?day?1; MitoQ, New Zealand; n = 10) or vehicle (dimethyl sulfoxide 0.7%; n = 10) administration by gavage was started 3 days after CBDL and continued for 4 wk. Three hours after the last administration, rats were euthanized. |
Dosage form |
10 mg?kg?1?day?1, p.o. |
Applications |
The weight of livers from rats treated with mitoquinone was significantly lower than that of livers from untreated cirrhotic animals and similar to that of controls, likely due to the reduction of hepatic inflammation. |
参考文献: [1]. Méndez D, et al. Mitoquinone (MitoQ) Inhibits Platelet Activation Steps by Reducing ROS Levels. Int J Mol Sci. 2020 Aug 27;21(17):6192 [2]. Turkseven S, et al. Mitochondria-targeted antioxidant mitoquinone attenuates liver inflammation and fibrosis in cirrhotic rats. Am J Physiol Gastrointest Liver Physiol. 2020 Feb 1;318(2):G298-G304. |
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