Niacin Ameliorates EHDPHP-Induced Oxidative Stress and Mitochondrial Dysfunction in H9C2 Cells

Area of Science:

• Environmental toxicology
• Cardiovascular research
• Nutritional science

Background:

• 2-Ethylhexyl diphenyl phosphate (EHDPHP) is a common flame retardant detected in the environment, with potential health risks.
• The cardiotoxic effects of EHDPHP and its molecular mechanisms in cardiomyocytes are not well understood.
• Niacin (NIA), a vitamin, has demonstrated antioxidant, anti-inflammatory, and mitochondrial protective properties.

Purpose of the Study:

• To investigate the toxicity of EHDPHP on H9C2 cardiomyocytes.
• To elucidate the molecular mechanisms underlying EHDPHP-induced cardiotoxicity.
• To evaluate the protective effects of Niacin (NIA) against EHDPHP-induced cardiac damage.

Main Methods:

• H9C2 cardiomyocytes were exposed to EHDPHP alone and in combination with varying concentrations of NIA.
• Cell viability, inflammatory cytokine levels, oxidative stress markers (ROS, MitoSOX, MDA), antioxidant enzyme activities, mitochondrial dynamics, biogenesis, mitophagy, and pyroptosis pathways were assessed.
• Bioinformatics analyses were employed to understand the regulatory network of EHDPHP-induced injury.

Main Results:

• EHDPHP exposure significantly reduced cell viability, induced oxidative stress, and disrupted the balance of pro- and anti-inflammatory cytokines.
• EHDPHP impaired mitochondrial dynamics and biogenesis, triggered excessive mitophagy, and activated pyroptosis.
• Niacin (NIA) dose-dependently mitigated EHDPHP's detrimental effects, restoring cell viability and alleviating molecular damage.

Conclusions:

• EHDPHP induces cardiomyocyte injury through a pathological cascade involving oxidative stress, inflammation, mitochondrial dysfunction, mitophagy, and pyroptosis.
• Niacin (NIA) confers cardioprotection by targeting multiple pathways disrupted by EHDPHP.
• This study highlights NIA as a potential nutritional intervention for mitigating cardiovascular risks associated with EHDPHP exposure.