Effects of Metformin on High Glucose- and UVA-Induced Oxidative Stress and Cellular Senescence in Rat Keratinocytes.

This study investigated the protective effects of metformin against combined high glucose (HG)- and UVA-induced cytotoxicity in fetal rat skin keratinocytes (FRSK cells), a model of diabetic photoaging. HG combined with UVA caused a synergistic loss of cell viability accompanied by marked increases in phosphorylation of AMP-activated protein kinase (p-AMPK), reactive oxygen species (ROS) generation, senescence-associated β-galactosidase (SA-β-Gal) activity, and Sirtuin 1 (SIRT1) expression. HG alone induced moderate cytotoxicity and senescence, whereas UVA alone under normal glucose conditions (NG + UVA) produced negligible ROS and minimal viability loss. Metformin improved cell viability under dual stress conditions in a dose-dependent manner, with maximal protection observed at 8 mM. In UVA-free cultures, metformin increased p-AMPK in both NG and HG, peaking at 8 mM. Under HG + UVA, p-AMPK was higher than in NG + UVA and HG alone, with no additional increase following metformin treatment. ROS accumulation occurred only under HG + UVA and was strongly suppressed by metformin, nearly to baseline at 8 mM. The HG + UVA-induced increases in SA-β-Gal activity and SIRT1 expression were reduced in parallel with ROS suppression. These findings suggest that metformin's cytoprotective effect in this model is primarily mediated by attenuation of ROS rather than by further AMPK activation, indicating an AMPK-independent antioxidant mechanism.

• Publication year

  2025

• Venue

  Biological and Pharmaceutical Bulletin

• Publication date

  2025-11-11

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.1248/bpb.b25-00372PMID 41224263
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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