Dithiothreitol reduces oxidative stress and necrosis caused by ultraviolet A radiation in L929 fibroblasts

Photochem Photobiol Sci. 2024 Feb;23(2):271-284. doi: 10.1007/s43630-023-00516-z. Epub 2024 Feb 2.

Abstract

Ultraviolet A (UVA) radiation, present in sunlight, can induce cell redox imbalance leading to cellular damage and even cell death, compromising skin health. Here, we evaluated the in vitro antioxidant and photochemoprotective effect of dithiothreitol (DTT). DTT neutralized the free radicals 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS·+), 2,2-diphenyl-1-picrylhydrazyl (DPPH·), and superoxide anion (O2·-) in in vitro assays, as well as the ferric ion (Fe3+) in the ferric reducing antioxidant power (FRAP) assay. We also evaluated the effect of DTT pre-treatment in L929 dermal fibroblasts and DTT (50 and 100 µM) led to greater cell viability following UVA-irradiation compared to cells that were untreated. Furthermore, the pre-treatment of cells with DTT prevented the increase of intracellular reactive oxygen species (ROS) production, including hydrogen peroxide (H2O2), lipid peroxidation, and DNA condensation, as well as the decrease in mitochondrial membrane potential (Δψm), that occurred following irradiation in untreated cells. The endogenous antioxidant system of cells was also improved in irradiated cells that were DTT pre-treated compared to the untreated cells, as the activity of the superoxide dismutase (SOD) and catalase (CAT) enzymes remained as high as non-irradiated cells, while the activity levels were depleted in the untreated irradiated cells. Furthermore, DTT reduced necrosis in UVA-irradiated fibroblasts. Together, these results showed that DTT may have promising use in the prevention of skin photoaging and photodamage induced by UVA, as it provided photochemoprotection against the harmful effects of this radiation, reducing oxidative stress and cell death, due mainly to its antioxidant capacity.

Keywords: Dithiothreitol; Necrosis; Oxidative stress; Photochemoprotection; UVA.

MeSH terms

  • Antioxidants* / metabolism
  • Antioxidants* / pharmacology
  • Dithiothreitol / metabolism
  • Dithiothreitol / pharmacology
  • Fibroblasts
  • Humans
  • Hydrogen Peroxide* / pharmacology
  • Necrosis
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Skin / radiation effects
  • Ultraviolet Rays

Substances

  • Antioxidants
  • Dithiothreitol
  • Hydrogen Peroxide
  • Reactive Oxygen Species