Protective Effects Of Hydrogen Sulfide/Lycium Barbarum Polysaccharide On Blue Light/PM2.5-induced Oxidative Damage

Background:Blue light is a common visible light in life.A growing number of studies have shown that long-term exposure to blue light will have toxic and side effects on human body,especially on the skin and retina in close contact with blue light.Although studies have shown that oxidative stress is an important factor in blue light-induced skin and retinal degeneration,the mechanism of blue light-induced skin and retinal degeneration and how to protect against it remain unclear.As a small molecule antioxidant,hydrogen sulfide（H₂S）can remove intracellular reactive oxygen species（ROS）and thus reduce intracellular oxidative stress and oxidative damage.Therefore,we want to further investigate whether exogenous H₂S can play a protective role against blue light-induced oxidative stress and oxidative damage in skin and retina.We also want to explore the protective effect of another antioxidant Lycium barbarum polysaccharide（LBP）on PM2.5-induced oxidative damage in skin cells.Objective:（1）The underlying mechanism of blue light-induced skin and retinal degeneration.（2）To investigate whether exogenous H₂S can protect skin and retina against blue light-induced oxidative stress and oxidative damage.（3）To explore the effect of LBP on PM2.5-induced oxidative damage in skin cells.Methods:（1）In vitro model:Human cuticle forming cells（HaCaT）and human retinal pigment epithelial cells（ARPE-19）were treated with blue light irradiation to establish light damage model.In addition,cells were pretreated with exogenous H₂S（Na HS as donor）to study the protective effect of H₂S on HaCaT cells and ARPE-19cells.Moreover,PM2.5-induced oxidative damage model of HaCaT cells was used to study the protective effect of LBP.（2）In vivo model:Sprague-Dawley（SD）rats were used as the object of blue light irradiation to establish the skin and retina light damage model,and the protective effects of H₂S on skin and retina were studied via intraperitoneal injection of H₂S.Results:（1）H₂S protects HaCaT cells from blue light-induced apoptosis.H₂S alleviates blue light-induced oxidative damage in HaCaT cells.It also inhibits the activation of ER stress-apoptosis signal induced by blue light.The ER stress-CHOP/Bax/Bcl-2 pathway is involved in blue light-triggered apoptosis in HaCaT cells.Blue light also induces autophagy in HaCaT cells,which is affected by ER stress.Autophagy further exacerbates blue light induced-cytotoxicity in HaCaT cells.Exogenous H₂S attenuates blue light-triggered skin cell apoptosis in rats.The in vivo experiments also confirm that H₂S inhibits blue light-induced oxidative stress,ER stress and autophagy.The above evidence demonstrates that the activation of oxidative stress-ER stress-autophagy-apoptotic signaling axis is the key mechanism of blue light-induced skin cell apoptosis and degeneration,and that exogenous H₂S has a protective role on blue light-induced skin damage and degeneration.（2）Exogenous H₂S relieves blue light-induced retinal degeneration and apoptosis,and inhibits blue light-triggered retinal oxidative stress and ER stress in rats.H₂S also inhibits blue light-triggered oxidative damage and inhibits blue light-induced ER stress-CHOP apoptotic signal activation in ARPE-19 cells.Further studies reveal that ER stress-CHOP apoptosis signal is involved in blue light-triggered apoptosis of ARPE-19cells.And H₂S reduces blue light-induced apoptosis in ARPE-19 cells,illustrating that exogenous H₂S also has a protective role on blue light-induced retinal damage and degeneration.（3）LBP reduces PM2.5-triggered apoptosis and increases cell survival,alleviates PM2.5-induced oxidative stress and oxidative damage,and inhibits PM2.5-induced ER stress in HaCaT cells.Further studies reveal that ER stress-CHOP apoptotic signal is involved in PM2.5-triggered apoptosis.Moreover,PM2.5-induced ER stress triggers autophagy in HaCaT cells.The autophagy inhibitor 3-MA can reduce PM2.5-induced apoptosis and death.LBP can also inhibit PM2.5-triggered autophagy in HaCaT cells.It is interesting that PM2.5 also triggers mitophagy and activates mitochondria-related apoptosis signal Bax/Bcl-2.The above data demonstrate that LBP can protect against PM2.5-induced skin cell oxidative damage.Conclusions:Blue light-induced oxidative stress,ER stress and autophagy are the main causes of skin and retina photodamage.In addition,exogenous H₂S has a great potential for skin and retina protection,which is closely related to its ability to regulate oxidative stress,ER stress and autophagy.Moreover,another antioxidant LBP also can protect against PM2.5-induced skin cell oxidative damage,further demonstrating the important role of oxidative stress.