Carbon monoxide (CO) inhibits hydrogen peroxide (HO)-induced oxidative stress and the activation of NF-κB signaling in lens epithelial cells.

Lens epithelial cells (LECs) play a critical role in the maintenance of clear crystalline lens. Previously, we reported that heme oxygenase-1 can protect LECs from hydrogen peroxide (HO)-induced apoptosis and oxidative stress; however, to the best of our knowledge, these protection mechanisms have not yet been explained. As carbon monoxide (CO) is an active by-product of heme degradation, we investigated its cytoprotective mechanism in both HO-treated human LECs (SRA 01/04) and primary rabbit LECs. CO-releasing molecule-3 was used as a CO releasing vehicle. The nuclear translocation of nuclear factor kappa B (NF-κB) p65 was monitored by Western blot and immunofluorescence staining. In addition, the levels of intracellular reactive oxygen species (ROS), antioxidants, and apoptotic molecules (Bax, Bcl-2, and caspase-3) were measured. Furthermore, cell apoptosis rate was quantified by flow cytometry. Our results disclosed that low concentrations of CO released from CO-releasing molecule-3 can attenuate NF-κB p65 nuclear translocation, reduce ROS generation, and enhance intracellular glutathione and superoxide dismutase levels. Moreover, low concentrations of CO inhibited HO-induced apoptotic molecules, thereby decreasing the apoptosis of LECs. These findings suggest that low concentrations of CO protect LECs from HO-induced oxidative damage by attenuating NF-κB p65 nuclear translocation, reducing the generation of ROS and apoptotic molecules, and restoring antioxidant enzyme levels, thereby inhibiting LECs apoptosis.