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Background <p>Ultraviolet-B (UVB) radiation is a principal environmental factor driving cutaneous photoaging and carcinogenesis, primarily by inducing oxidative stress and DNA damage. This study investigated the potential of theophylline, a clinically established methylxanthine with known antioxidant and anti-inflammatory properties, to protect Normal Human Dermal Fibroblasts (NHDF) from UVB-induced genotoxic stress.</p> Methods <p>NHDF cultures were pre-treated for 24&#xa0;h with theophylline at concentrations of 10–200 micromolar (µM) and subsequently exposed to UVB irradiation (100&#xa0;mJ/cm²). A comprehensive panel of cellular assays was employed to evaluate cytotoxicity (MTT, LDH, ATP, caspase-3/7 assays), oxidative stress (ROS, MDA, GSH/GSSG ratio, SOD, catalase activity), genotoxicity (Comet and micronucleus assays), mitochondrial function (MMP, NAD⁺/NADH ratio), inflammatory responses (IL-6, IL-8, TNF-α, IL-1β), and apoptosis (TUNEL assay).</p> Results <p>UVB irradiation induced marked cytotoxicity, oxidative stress, mitochondrial dysfunction, and significant DNA damage in NHDF cells. Theophylline pre-treatment significantly attenuated these deleterious effects in a concentration-dependent manner. Specifically, theophylline restored cell viability, preserved mitochondrial function, reduced ROS generation and lipid peroxidation, enhanced endogenous antioxidant defenses, suppressed the release of pro-inflammatory cytokines, and inhibited DNA damage and apoptosis.</p> Conclusion <p>The results demonstrate that theophylline confers broad cytoprotective and genoprotective effects against UVB-mediated toxicity in human dermal fibroblasts. By mitigating oxidative stress, stabilizing mitochondrial function, suppressing inflammation, and preventing apoptosis, theophylline shows significant promise as a novel photoprotective agent for mitigating solar-induced skin damage and preventing UVB-mediated genomic instability.</p>

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Photoprotective and genoprotective effects of theophylline against UVB-induced damage in normal human dermal fibroblasts

  • 期刊论文

  • 发表日期：

    2026年2月24日

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  • Farzaneh Motafeghi,
  • Ehsan Ghassemi Barghi,
  • Jafar Gholami Gharab,
  • Farima Vafaeinezhad,
  • Nasrin Ghassemi Barghi

摘要

Background

Ultraviolet-B (UVB) radiation is a principal environmental factor driving cutaneous photoaging and carcinogenesis, primarily by inducing oxidative stress and DNA damage. This study investigated the potential of theophylline, a clinically established methylxanthine with known antioxidant and anti-inflammatory properties, to protect Normal Human Dermal Fibroblasts (NHDF) from UVB-induced genotoxic stress.

Methods

NHDF cultures were pre-treated for 24 h with theophylline at concentrations of 10–200 micromolar (µM) and subsequently exposed to UVB irradiation (100 mJ/cm²). A comprehensive panel of cellular assays was employed to evaluate cytotoxicity (MTT, LDH, ATP, caspase-3/7 assays), oxidative stress (ROS, MDA, GSH/GSSG ratio, SOD, catalase activity), genotoxicity (Comet and micronucleus assays), mitochondrial function (MMP, NAD⁺/NADH ratio), inflammatory responses (IL-6, IL-8, TNF-α, IL-1β), and apoptosis (TUNEL assay).

Results

UVB irradiation induced marked cytotoxicity, oxidative stress, mitochondrial dysfunction, and significant DNA damage in NHDF cells. Theophylline pre-treatment significantly attenuated these deleterious effects in a concentration-dependent manner. Specifically, theophylline restored cell viability, preserved mitochondrial function, reduced ROS generation and lipid peroxidation, enhanced endogenous antioxidant defenses, suppressed the release of pro-inflammatory cytokines, and inhibited DNA damage and apoptosis.

Conclusion

The results demonstrate that theophylline confers broad cytoprotective and genoprotective effects against UVB-mediated toxicity in human dermal fibroblasts. By mitigating oxidative stress, stabilizing mitochondrial function, suppressing inflammation, and preventing apoptosis, theophylline shows significant promise as a novel photoprotective agent for mitigating solar-induced skin damage and preventing UVB-mediated genomic instability.