Trivalent arsenicals induce skin toxicity through thiol depletion

Area of Science:

• Environmental Toxicology
• Dermatology
• Biochemistry

Background:

• Arsenic is a prevalent environmental toxin linked to skin conditions.
• Trivalent arsenicals (As^III, MMA^III) are known for their toxicity.
• Understanding the mechanism of arsenic-induced dermal toxicity is crucial for developing treatments.

Purpose of the Study:

• To investigate the dermal toxicity of trivalent arsenicals (As^III and MMA^III).
• To elucidate the underlying mechanisms of arsenic-induced skin damage.
• To evaluate the protective effects of antioxidants against arsenical dermal toxicity.

Main Methods:

• Utilized human keratinocyte cell line (HaCaT) and ex vivo porcine skin models.
• Assessed cell viability, apoptosis, necrosis, reactive oxygen species (ROS) generation, and glutathione (GSH) levels.
• Tested the efficacy of antioxidants, including Vitamin C and thiol-containing compounds like DMSA.

Main Results:

• As^III and MMA^III induced dose-dependent apoptosis and necrosis in HaCaT cells and porcine skin.
• Arsenicals increased ROS production and depleted GSH, indicating oxidative stress and thiol depletion.
• Thiol-containing compounds, particularly DMSA, effectively mitigated arsenical cytotoxicity and tissue damage.

Conclusions:

• Thiol depletion is a critical mechanism in trivalent arsenical-induced dermal toxicity.
• DMSA demonstrates significant protective effects against As^III and MMA^III-induced skin damage.
• DMSA holds potential for alleviating arsenic-induced skin lesions and diseases.