Introduction: 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 down regulation 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 clearly demonstrate that exposure to p-CYM over time promotes oxidative stress by down regulating antioxidants genes as shown in PON-1 and also stimulates inflammation a key process during the initiation and progression of atherosclerosis.
Introduction: We previously reported that intake of quercetin during moderate exercise modulate lipid metabolism in LDLr -/- C57BL6 mice. The current study investigates the role of strenuous exercise and quercetin on lipids metabolism. Study Design: 40 mice were divided into four groups (10 each). These groups are as follows: Control mice, left untreated; control quercetin group, orally supplied with 100 μg/day of quercetin without exercising; exercise group without quercetin, and exercise group with quercetin supplements. The exercise groups were run on a treadmill for 30 minutes, 20-30m/m/ 5 days/week for two month. All animals were on normal mouse chow, at the end of the two month treatment, tissues were collected and expressions of genes associated lipid metabolism were analyzed and the proteins Western Blotting were determined. Results: PCSK9 mRNA level was significantly up-regulated as the result of combination of exercise and quercetin intake (p< 0.05) or quercetin alone. ANGPLT3 mRNA level did not show any significant changes as a result of exercise or quercetin. However, ANGPLT4 mRNA levels significantly down-regulated with the combination after 8 weeks of exercise and quercetin intake compared to both control and Exercise (p < 0.05). ANGPLT4 also decreased with quercetin intake; however this change is not significant. There was a slight change in ANGPLT 4 levels in the exercise group. Conclusion: The combination of strenuous exercise and quercetin intake did not show any positive affect on LDL (plasma LDL levels were measured; however not presented above), this was also reflected by the upregulation of the PCSK9 gene expression. Lipoprotein related genes differentially modulated with the strenuous exercise and quercetin intake. This data suggest that the combination of strenuous exercise and quercetin intake unfavorably impact LDL associated PCSK9 gene; however differentially affect ANGPLT4 levels with the exercise or the combination.
Di-n-butyl phthalate (DBP) is used in air fresheners. It is a colorless oily compound which also used for manufacturing bendable plastics. DBP can cause low acute or chronic toxicity; however, the effect of DBP on humans in the form of air fresheners is not well studied. The effect of DBP on the human cardiovascular system has not been studied. Macrophages are involved in atherosclerosis progression and development; murine macrophages (RAW 264.7) were used for this study. The macrophages were treated with 10uM, 20uM and 50uM DBP for 6 hours, 12 hours and 24 hours. Genes involved in inflammation and antioxidant activity like TNF-a, MCP-1, VCAM-1, NF-kB, PON1, SOCS were analyzed after treatment. macrophages showed statistically significant increases in TNF-alpha expression (p≤ 0.05) after 24 hour treatment with DBP. The expression of NF-kB showed a significant increase in response to DBP treatment (p≤ 0.05) at 24 hours. MCP-1 and VCAM-1 gene expressions were also upregulated after exposure to DBP. Interestingly, catalase gene expression was upregulated in all treatments after 24 hours of exposure however PON-1 gene expression showed differential upregulation responses. Our data clearly suggest that DBP induces inflammation in macrophages. PON1 and catalase upregulated gene expression indicative of a compensatory response to oxidative stress associated with the treatment. Oxidative stress and inflammation mediated macrophages responses strongly linked to atherosclerosis pathogenesis.
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