Needle-Free Injection of Metformin Ameliorates Skin Photoaging Through Inhibition of Ferroptosis and Oxidative Stress.
Discov Med
; 36(184): 1080-1090, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38798266
ABSTRACT
BACKGROUND:
Skin photoaging is a complex process of skin aging caused by continuous exposure to ultraviolet (UV) radiation through oxidative stress and other pathways, yet effective treatments are scarce. Metformin is a drug with both anti-senescence and antioxidant functions; however, there are fewer studies on photoaging. The study aimed to investigate the role of needle-free injection of metformin in alleviating ultraviolet radiation B (UVB) induced skin photoaging, and to explore the mechanisms through which metformin alleviates fibroblast photoaging by inhibiting ferroptosis and oxidative stress.METHODS:
In our study, we initially performed bioinformatic analysis on the gene expression profile (GSE38308), and our RNA sequencing (RNA-Seq) found that photoaging is associated with ferroptosis. We investigated the potential skin-protective mechanism of metformin by utilizing a UVB-induced rat skin photoaging model and human skin fibroblasts (HSF) treated with UVB. For in vitro experiments, cellular senescence was detected using SA-ß-galactosidase staining and p16 in western blot. Ferroptosis and oxidative stress were assessed via western blot (glutathione Peroxidase 4 (GPX4) and nuclear factor erythroid-2-related factor 2 (Nrf2)), reactive oxygen species (ROS) levels, transmission electron microscope, Lillie's staining, and immunofluorescence staining. During in vivo experiments, metformin was administered by needle-free jet injectors injected into the backs of rats. The effectiveness of metformin was detected using the Masson staining and western blot.RESULTS:
We found that the ferroptosis pathway was closely associated with photoaging through bioinformatics analysis. In the UVB-induced photoaging HSF cells, treatment with metformin exhibits the following effects a reduction in blue-stained granules in SA-ß-galactosidase staining and a decrease in the expression of p16, indicating a reduction in cellular senescence. Moreover, metformin leads to decreased ROS levels and increased expression of the oxidative stress-related protein Nrf2, suggesting inhibition of oxidative stress within the cells. Additionally, metformin results in an elevation of GPX4 expression, a decrease in blue-stained granules in Lillie's staining, and a reduction in ferroptosis-associated mitochondrial damage, indicating a decline in ferroptosis. Needle-free injection of metformin could directly achieve therapeutic effects by affecting HSF cells in the dermis. The needle-free injection of metformin treatment effectively improved the photoaging skin in rats compared to the photoaging group, ameliorated oxidative stress, and reduced ferroptosis.CONCLUSIONS:
Our data highlights a novel needle-free injection of metformin that improves photoaging and has good therapeutic potential.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Rayos Ultravioleta
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Envejecimiento de la Piel
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Estrés Oxidativo
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Ferroptosis
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Metformina
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Discov Med
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Discov. medicin.
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Discovery medicine
Año:
2024
Tipo del documento:
Article
País de afiliación:
China