DISCLAIMERS

contact us >>

Mitigating Radiation Damage in Human Skin: Metformin's Impact on DNA Integrity, Tissue Preservation, and Fibrosis

Alexa Rivera del Rio Hernandez MD; Mahajan, Naresh PhD; Bosco, Samantha BS; Egro, Francesco M. MBChB, MSc, MRCS; Gusenoff, Jeffrey MD; Rubin, J. Peter MD, FACS, MBA; Ejaz, Asim PhD
University of Pittsburgh
2025-01-10

Presenter: Alexa Rivera del Rio Hernandez

Affidavit:
I certify that the work has not been published and presented.

Director Name: Vu T Nguyen

Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: Aesthetics

Radiation-induced damage to human skin remains a critical challenge in therapeutic and accidental exposure to ionizing radiation. High-dose X-ray exposure (10 Gy) disrupts skin integrity through DNA double-strand breaks, oxidative stress, and apoptosis, leading to reduced thickness, increased fibrosis, and compromised function. Developing effective interventions is essential to mitigate these effects and support tissue recovery. Metformin, a widely used anti-diabetic medication, has demonstrated potential as a radioprotective agent through its ability to reduce DNA damage, preserve tissue structure, and modulate fibrosis-related pathways.

In this study, we investigated the efficacy of topical metformin in addressing radiation-induced DNA damage, skin atrophy, and fibrosis using an ex vivo human skin perfusion system. Skin flaps were exposed to 10 Gy of X-ray radiation and divided into three groups: irradiation only, irradiation with a control cream, and irradiation with metformin cream. Biopsies collected on days 2, 7, 11, and 13 post-irradiation were analyzed for DNA damage using TUNEL staining and γH2AX immunohistochemistry, tissue thickness via histological measurements, and fibrosis markers through TGF-β immunohistochemistry.

Metformin-treated skin exhibited a significant reduction in DNA damage markers, preserved thickness, and suppressed TGF-β overexpression compared to untreated irradiated skin. These protective effects were most pronounced at later time points, correlating with reduced apoptosis, enhanced DNA repair, and decreased collagen deposition.

In conclusion, metformin effectively mitigates radiation-induced genetic damage, atrophy, and fibrosis, offering a multifaceted approach to protect skin integrity and function. This study underscores metformin's potential as a therapeutic agent in clinical radiotherapy and accidental radiation exposure scenarios.

Ohio,Pennsylvania,West Virginia,Indiana,Kentucky,Pennsylvania American Society of Plastic Surgeons

OVSPS Conference