Neuroprotective Activity of Grape Seed and Skin Extract Against Lithium Exposure Using Proteomic Research

Lithium (Li) has raised scientific concern because it represents a serious problem threatening human health. This study aimed firstly at analyzing and potentially quantifying the impact of Li and grape seed and skin extract (GSSE) separately and, secondly, describing the possible neuroprotective activity of GSSE against Li toxicity. To this end, rats were exposed for 30 days to different Li concentrations (0, 2, and 100 mg/kg bw), to GSSE (4000 mg/kg bw), and to binary mixture of Li and GSSE. Liquid chromatography (HPLC-MS/MS) analysis used for GSSE showed that 15 phenolic compounds are present in the extract. Significant modifications of proteins were detected in the brain using proteomics research after treatment. Proteins were successfully identified by a linear ion trap-Orbitrap mass spectrometer. These proteins can be roughly related to oxidative stress, glycolysis, signaling pathway, and inflammation. Additionally, proteins involved in cell junction such as myosin, spectrin, tubulin, ERM-binding phosphoprotein, and dynein were also affected by Li exposure. Dose response was detected for most expressed proteins after Li treatment. In contrast, GSSE induced the expression and/or the stabilization of some proteins changed after Li treatment in the brain showing its neuroprotective activity. These data demonstrate that proteomic analysis is a powerful tool to provide valuable insights into mechanisms of toxicity of Li in the nervous system of Wistar rats. To our knowledge, this is the first evidence of using GSSE as neuroprotective model against Li toxicity. These findings provide impetus for future investigation on GSSE against other toxic chemicals.