Background: 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.
Objective: 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.
Methods: 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.
Results: We showed that resveratrol prevented the increase in ROS production, the decrease of mitochondrial membrane potential (ΔΨm), 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.
Conclusions: In summary, our study demonstrates that resveratrol prevents ammonia-induced cytotoxicity, as well as supports the role of resveratrol on mitochondrial/cellular redox functionality.
Keywords: Ammonia; Astroglial cells; Mitochondria; Oxidative stress; Resveratrol.