Gramicidin A attenuates oxidative stress, mitochondrial dysfunction, DNA damage, and inflammation in 6-OHDA-induced...

Oxidative stress and mitochondrial dysfunction are major contributors to neurodegenerative diseases, and this study investigated the protective potential of Gramicidin A in a 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y cellular injury model relevant to Parkinson's disease (PD).

Following the 3-(4,5-Dimethyl-2-thiazolyl)- 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay to determine the appropriate Gramicidin A concentration, cells were evaluated for oxidative stress parameters, including reactive oxygen species (ROS), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GPx), as well as mitochondrial membrane potential (MMP), the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG), and inflammatory stress markers including interleukin-6 (IL-6), IL-8, and transforming growth factor-beta (TGF-β). Exposure to 6-OHDA significantly reduced cell viability, increased ROS production, and disrupted oxidative balance (p < 0.0001). In contrast, both pre- and post-treatment with Gramicidin A reduced ROS levels, improved TAS, TOS, and OSI values, decreased MDA levels, increased GSH levels, and modulated GPx activity (p < 0.0001) in SH-SY5Y cells. Gramicidin A treatment also modulated the JC-10 red/green fluorescence ratio, suggesting changes in MMP, decreased 8-OHdG levels, and a significant reduction in 6-OHDA-induced elevations in IL-6, IL-8, and TGF-β levels in SH-SY5Y cells (p < 0.0001).

These findings suggest that Gramicidin A attenuates 6-OHDA-induced cellular injury in SH-SY5Y cells by modulating oxidative stress, mitochondrial membrane potential-related changes, oxidative DNA damage, and inflammatory stress responses.