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p-Cymene Modulate Oxidative Stress and Inflammation in Murine Macrophages: Potential Implication in Atherosclerosis
Tong Wu1, Zahra Mazhar1, Dhuha Alsayrafi1
1Department of Clinical Laboratory and Nutritional Sciences, University of Massachusetts, Lowell, MA, United States.
Background:
p-Cymene (p-CYM) is a common chemical used in air fresheners.
Objective:
The study was designed to investigate the molecular effect of p-CYM on macrophages.
Materials And Methods:
Macrophages (RAW 264.7) were treated with p-CYM (50 uM/L, 150 uM/L and 250 uM/L) for 6 hours, and 24 hours). Gene involved in inflammation, such as the Tumor Necrosis Factor-alpha (TNF-α), and the Monocyte Chemoattractant Protein-1 (MCP-1) and other genes known for their antioxidant activity such as the Paraoxonase 1 (PON-1) were analyzed.
Results:
Cells treated with p-CYM have shown 30% up-regulation of MCP-1 after 24 hour of exposure; and also a differential up-regulation of TNF-α. However, treatment with p-CYM has resulted in a considerable (37%) dose-dependent downregulation of PON-1 after 24 hours of exposure. PON-1 is known for its antioxidant properties protecting High-Density Lipoproteins (HDL) from oxidation.
Conclusion:
Our findings demonstrate that exposure to p-CYM over time promotes oxidative stress by downregulating antioxidants genes as shown in PON-1 and also stimulates inflammation, a key process during the initiation and progression of atherosclerosis.
Insights
p-Cymene exposure downregulates antioxidant genes like PON-1 and upregulates inflammatory genes, promoting oxidative stress and inflammation, key factors in atherosclerosis development.
Area of Science:
- Immunology
- Molecular Biology
- Oxidative Stress Research
Background:
- p-Cymene (p-CYM) is a widely used chemical found in air fresheners.
- Macrophages play a crucial role in immune responses and inflammation.
Purpose of the Study:
- To investigate the molecular effects of p-CYM on macrophage gene expression.
- To assess the impact of p-CYM on inflammatory and antioxidant pathways in macrophages.
Main Methods:
- RAW 264.7 macrophages were exposed to varying concentrations of p-CYM (50, 150, 250 uM/L) for 6 and 24 hours.
- Gene expression analysis was performed for inflammatory markers (TNF-α, MCP-1) and antioxidant genes (PON-1).
Main Results:
- p-CYM exposure led to a 30% upregulation of MCP-1 and differential upregulation of TNF-α after 24 hours.
- A significant, dose-dependent downregulation (37%) of the antioxidant gene PON-1 was observed after 24 hours.
- Paraoxonase 1 (PON-1) is critical for protecting High-Density Lipoproteins (HDL) from oxidation.
Conclusions:
- p-Cymene exposure promotes oxidative stress by downregulating PON-1, an important antioxidant gene.
- p-CYM stimulates inflammation, indicated by increased TNF-α and MCP-1 expression.
- These findings suggest p-CYM may contribute to atherosclerosis initiation and progression through oxidative stress and inflammation.
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