a Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Nutr Neurosci. 2018 May;21(4):276-285. doi: 10.1080/1028415X.2017.1284375. Epub 2017 Feb 6.
Resveratrol is a polyphenolic compound that presents several protective effects in the central nervous system, including gliotoxicity associated to hyperammonemia, a key element for the development of hepatic encephalopathy. In this condition, mitochondrial dysfunction leads to a reactive oxygen species (ROS) overproduction, which, in turn, exacerbates mitochondrial failure and causes cellular damage.
This study sought to determine whether prevention of mitochondrial dysfunction and the maintenance of cellular redox status by resveratrol contribute to its protective action toward ammonia toxicity.
C6 astrocyte cell line was pre-incubated in the presence or absence of resveratrol (100 μM) for 1 hour. After pre-incubation, resveratrol was maintained and 5 mM ammonia was added for 24 hours, followed by the evaluation of ROS production, mitochondrial functionality, antioxidant enzymatic and non-enzymatic defenses, energy metabolic parameters, and genotoxicity.
We showed that resveratrol prevented the increase in ROS production, the decrease of mitochondrial membrane potential (ΔΨ), and bioenergetics deficit caused by ammonia in C6 astroglial cells. In addition, resveratrol avoided the ammonia-induced upregulation of NOX activity and impairment in enzymatic and non-enzymatic antioxidant defenses. Ammonia also induced DNA damage that was prevented by resveratrol, indicating its genoprotective effect.
In summary, our study demonstrates that resveratrol prevents ammonia-induced cytotoxicity, as well as supports the role of resveratrol on mitochondrial/cellular redox functionality.
白藜芦醇是一种多酚化合物，在中枢神经系统中具有多种保护作用，包括与高氨血症相关的神经毒性，高氨血症是肝性脑病发展的关键因素。在这种情况下，线粒体功能障碍导致活性氧（ROS）的过度产生，这反过来又加剧了线粒体衰竭并导致细胞损伤。
本研究旨在确定白藜芦醇是否通过预防线粒体功能障碍和维持细胞氧化还原状态来促进其对氨毒性的保护作用。
C6 星形胶质细胞系在存在或不存在白藜芦醇（100 μM）的情况下预先孵育 1 小时。预孵育后，维持白藜芦醇并添加 5 mM 氨 24 小时，然后评估 ROS 产生、线粒体功能、抗氧化酶和非酶防御、能量代谢参数和遗传毒性。
我们表明，白藜芦醇可预防 ROS 产生增加、线粒体膜电位（ΔΨ）降低和氨引起的 C6 星形胶质细胞生物能缺陷。此外，白藜芦醇避免了氨诱导的 NOX 活性上调和酶和非酶抗氧化防御的损害。氨还诱导了 DNA 损伤，白藜芦醇可预防这种损伤，表明其具有遗传保护作用。
总之，我们的研究表明，白藜芦醇可预防氨诱导的细胞毒性，并支持白藜芦醇对线粒体/细胞氧化还原功能的作用。
