Melatonin mitigates UV-induced tumorigenesis and suppresses hearing function deterioration in Xpa-deficient mice

Area of Science:

• Genetics and Molecular Biology
• Dermatology
• Pharmacology

Background:

• Xeroderma pigmentosum (XP) involves impaired DNA repair of UV-induced damage and increased oxidative stress.
• XP cells exhibit heightened sensitivity to reactive oxygen species (ROS) and inflammatory responses.
• UV exposure in XP-A model mice significantly upregulates inflammatory response genes.

Purpose of the Study:

• To identify antioxidant and anti-inflammatory agents that may improve symptoms in XP.
• To investigate the therapeutic potential of melatonin in mitigating XP cellular and clinical manifestations.

Main Methods:

• Tested antioxidants for reducing 4-nitroquinoline 1-oxide (4NQO)-induced oxidative cytotoxicity and UV-induced DNA damage in XP-A cells.
• Evaluated melatonin's effects on UV-induced cytotoxicity, ROS production, skin tumorigenesis, and neurological symptoms in Xpa-deficient mice and MEF cells.

Main Results:

• Melatonin and nicotinamide reduced 4NQO-induced oxidative cytotoxicity.
• Melatonin improved UV-induced ROS production and cytotoxicity in Xpa-deficient MEF cells.
• Melatonin administration mitigated UV-induced skin inflammation, tumorigenesis, and hearing loss in Xpa-deficient mice.

Conclusions:

• Melatonin demonstrates significant anti-inflammatory and antioxidant properties.
• Melatonin can alleviate key symptoms associated with Xeroderma pigmentosum.
• These findings suggest melatonin as a potential therapeutic agent for XP.