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Piceatannol promotes hepatic and renal AMPK/SIRT1/PGC-1α mitochondrial pathway in rats exposed to reserpine or gamma-radiation
International Journal of Immunopathology and Pharmacology ( IF 3.0 ) Pub Date : 2021-05-13 , DOI: 10.1177/20587384211016194
Enas Mahmoud Moustafa 1 , Engy Refaat Rashed 2 , Rasha Refaat Rashed 2 , Nesreen Nabil Omar 3
Affiliation  

Human exposure to radio-therapeutic doses of gamma rays can produce late effects, which negatively affect cancer patients’ quality of life, work prospects, and general health. This study was performed to explore the role of Piceatannol (PIC) in the process of “mitochondrial biogenesis” signaling pathway as possible management of disturbances induced in stressed animal model(s) either by gamma-irradiation (IR) or administration of reserpine (RES); as a mitochondrial complex-I inhibitor. PIC (10 mg/kg BW/day; orally) were given to rats for 7 days, after exposure to an acute dose of γ-radiation (6 Gy), or after a single reserpine injection (1 g/kg BW; sc). Compared to reserpine or γ-radiation, PIC has attenuated hepatic and renal mitochondrial oxidative stress denoted by the significant reduction in the content of lipid peroxides and NO with significant induction of SOD, CAT, GSH-PX, and GR activities. PIC has also significantly alleviated the increase of the inflammatory markers, TNF-α and IL-6 and apoptotic markers, cytochrome c, and caspase-3. The decrease of oxidative stress, inflammation, and apoptotic responses were linked to a significant amelioration in mitochondrial biogenesis demonstrated by the increased expression and proteins’ tissue contents of SIRT1/p38-AMPK, PGC-1α signaling pathway. The results are substantiated by the significant amelioration in mitochondrial function verified by the higher levels of ATP content, and complex I activity, besides the improvement of hepatic and renal functions. Additionally, histopathological examinations of hepatic and renal tissues showed that PIC has modulated tissue architecture after reserpine or gamma-radiation-induced tissue damage. Piceatannol improves mitochondrial functions by regulating the oxidant/antioxidant disequilibrium, the inflammatory and apoptotic responses, suggesting its possible use as adjuvant therapy in radio-therapeutic protocols to attenuate hepatic and renal injuries.



中文翻译:


白皮杉醇促进利血平或伽马辐射大鼠肝肾 AMPK/SIRT1/PGC-1α 线粒体通路



人体接触放射治疗剂量的伽马射线会产生后期影响,对癌症患者的生活质量、工作前景和总体健康产生负面影响。本研究旨在探讨白皮杉醇 (PIC) 在“线粒体生物发生”信号通路过程中的作用,作为可能的管理应激动物模型中通过伽马射线照射 (IR) 或利血平 (RES) 引起的干扰的方法);作为线粒体复合物 I 抑制剂。在暴露于急性剂量的 γ 辐射 (6 Gy) 后或单次注射利血平 (1 g/kg BW; sc) 后,给予大鼠 PIC(10 mg/kg BW/天;口服)7 天。 。与利血平或γ-辐射相比,PIC 减轻了肝和肾线粒体氧化应激,表现为脂质过氧化物和 NO 含量显着降低,并显着诱导 SOD、CAT、GSH-PX 和 GR 活性。 PIC还显着减轻了炎症标志物TNF-α和IL-6以及细胞凋亡标志物细胞色素c和caspase-3的增加。 SIRT1/p38-AMPK、PGC-1α 信号通路的表达和蛋白质组织含量的增加证明了氧化应激、炎症和凋亡反应的减少与线粒体生物发生的显着改善有关。除了肝功能和肾功能的改善外,ATP 含量和复合物 I 活性水平的提高也证实了线粒体功能的显着改善,证实了这一结果。此外,肝和肾组织的组织病理学检查表明,PIC 在利血平或伽马辐射引起的组织损伤后调节组织结构。 白皮杉醇通过调节氧化剂/抗氧化剂不平衡、炎症和细胞凋亡反应来改善线粒体功能,这表明它可以作为放射治疗方案中的辅助治疗,以减轻肝和肾损伤。

更新日期:2021-05-14
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