Radioprotective effect of the anti-diabetic drug metformin

PLoS One. 2024 Jul 23;19(7):e0307598. doi: 10.1371/journal.pone.0307598. eCollection 2024.

Abstract

Metformin is a biguanide currently used in the treatment of diabetes mellitus type 2. Besides its anti-glycemic effects, metformin has been reported to induce different cellular pleiotropic effects, depending on concentration and time of treatment. Here we report one administration of metformin (0.5 mM) has radioprotective effects in vitro on BJ human fibroblasts, increasing DNA damage repair and increasing SOD1 expression in the nucleus. Importantly, metformin (200 mg/kg) pre-administration for only 3 days in wild type 129/sv mice, decreases the formation of micronuclei in bone marrow cells and DNA damage in colon and lung tissues compared to control irradiated mice at sub-lethal and lethal doses, increasing the overall survival fraction by 37% after 10Gy total body irradiation. We next pre-treated with metformin and then exposed 129/sv mice, to a galactic cosmic rays simulation (GCRsim), at the NASA Space Radiation Laboratory (NSRL). We found metformin pre-treatment decreases the presence of bone marrow micronuclei and DNA damage in colon and lung tissues and an increase of 8-oxoguanine DNA glycosylase-1 (OGG1) expression. Our data highlight a radioprotective effect of metformin through an indirect modulation of the gene expression involved in the cellular detoxification rather than its effects on mitochondria.

MeSH terms

  • Animals
  • Cell Line
  • DNA Damage* / drug effects
  • DNA Damage* / radiation effects
  • DNA Repair / drug effects
  • DNA Repair / radiation effects
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects
  • Humans
  • Hypoglycemic Agents* / pharmacology
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung / radiation effects
  • Male
  • Metformin* / pharmacology
  • Mice
  • Micronucleus Tests
  • Radiation-Protective Agents* / pharmacology
  • Superoxide Dismutase / metabolism

Substances

  • Metformin
  • Radiation-Protective Agents
  • Hypoglycemic Agents
  • Superoxide Dismutase