Some natural compounds exert their antioxidant effect by altering aquaporins functional properties

The ability of some aquaporins (AQPs) to facilitate the diffusion of H2O2 from the producing cells to the extracellular fluid has been recently demonstrated. Accordingly, this significant AQPs property may have a beneficial effect in promoting Reactive Oxygen Species (ROS) scavenging. Nevertheless, some AQPs aspects remain unsolved and, in this scenario, the identification and localization of different AQPs acting as peroxiporins, their functional role in eustress and distress, as well as the identification of chemical antioxidant compounds capable to regulate AQP gating are still the main features to disclose. In light of these considerations, this study aimed at investigating the potential effect of well-known natural compounds in modulating the activity of AQPs. From an experimental standpoint, in this work the expression of mRNA and proteins of different AQPs in HeLa cells, the functional experiments of water (and H2O2) permeability using stopped-flow light scattering method and the gating of AQPs in the presence/absence of oxidative stress have been evaluated. The obtained results suggest that oxidative stress reduced water AQP-mediated permeability and the effectiveness of the analyzed compounds to promote AQPs gating. Therefore, this study could lead to the identification of a novel therapeutic target for the treatment of cancer and degenerative diseases, since the positive regulation of AQPs avoids the accumulation of ROS within the cells.