Protective Effect of Curcumin on Pulmonary and Cardiovascular Effects Induced by Repeated Exposure to Diesel Exhaust Particles in Mice

Background/Aim: There is strong epidemiological and clinical evidence that components of the cardiovascular system are adversely affected by particulate air pollutants through the generation of inflammation and oxidative stress. Emodin (1,3,8-trihydroxy-6-methylanthraquinone), which is commonly found in the roots of rhubarb plant, has strong antioxidant and anti-inflammatory effects. However, its possible protective effect on the cardiovascular effect of particulate air pollutants has never been reported before. Methods: We tested, in Tuck-Ordinary mice, the possible ameliorative effect of emodin on the acute (24h) cardiovascular effects of diesel exhaust particles (DEP, 1 mg/kg) or saline (control). Emodin (4 mg/kg) was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty four h following DEP exposure, several cardiovascular endpoints were assessed. Results: Emodin significantly prevented the increase of leukocyte (n=8, P<0.001) and erythrocyte (n=8, P<0.01) numbers caused by DEP. Likewise, emodin abrogated DEP-induced increase of heart tissue levels of interleukin 1β (n=8, P<0.01) and tumour necrosis factor α (n=8, P<0.05), and significantly mitigated the change of the activities of antioxidant enzymes superoxide dismutase (n=8, P<0.001) and glutathione reductase (n=8, P<0.05). Emodin abolished the in vivo prothrombotic effect of DEP in pial arterioles (n=6, P<0.01) and venules (n=6, P<0.001). Similarly, emodin prevented platelet aggregation in vitro in whole blood (n=4-5, P<0.01), and the shortening of activated partial thromboplastin time (n=4, P<0.001) and prothrombin time (n=4, P<0.01) caused by DEP. Conclusion: We conclude that emodin treatment has consistently protected against DEP-induced impairment of vascular and cardiac homeostasis in mice. Our study provides experimental evidence that the use of functional food such as emodin, pending further studies, can be considered a useful agent and may have the potential to protect or mitigate the cardiovascular detrimental effects observed in people living in cities with high concentrations of particulate air pollution.

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Thrombosis and systemic and cardiac oxidative stress and DNA damage induced by pulmonary exposure to diesel exhaust particles and the effect of nootkatone thereon

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00313.2017 ◽

2018 ◽

Vol 314 (5) ◽

pp. H917-H927 ◽

Cited By ~ 11

Author(s):

Abderrahim Nemmar ◽

Suhail Al-Salam ◽

Sumaya Beegam ◽

Priya Yuvaraju ◽

Badreldin H. Ali

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Protective Effect ◽

Heme Oxygenase ◽

Diesel Exhaust ◽

Diesel Exhaust Particles ◽

Heme Oxygenase 1 ◽

Nuclear Factor ◽

Intratracheal Administration ◽

Exhaust Particles

Adverse cardiovascular effects of particulate air pollution persist even at lower concentrations than those of the current air quality limit. Therefore, identification of safe and effective measures against particle-induced cardiovascular toxicity is needed. Nootkatone is a sesquiterpenoid in grapefruit with diverse bioactivities including anti-inflammatory and antioxidant effects. However, its protective effect on the cardiovascular injury induced by diesel exhaust particles (DEPs) has not been studied before. We assessed the possible protective effect of nootkatone (90 mg/kg) administered by gavage 1 h before intratracheal instillation of DEPs (30 μg/mouse). Twenty-four hours after the intratracheal administration of DEPs, various thrombotic and cardiac parameters were assessed. Nootkatone inhibited the prothrombotic effect induced by DEPs in pial arterioles and venules in vivo and platelet aggregation in whole blood in vitro. Also, nootkatone prevented the shortening of activated partial thromboplastin time and prothrombin time induced by DEPs. Nootkatone inhibited the increase of plasma concentration of fibrinogen, plasminogen activator inhibitor-1, interleukin-6, and lipid peroxidation induced by DEPs. Immunohistochemically, hearts showed an analogous increase in glutathione and nuclear factor erythroid-derived 2-like 2 expression by cardiac myocytes and endothelial cells after DEP exposure, and these effects were enhanced in mice treated with nootkatone + DEPs. Likewise, heme oxygenase-1 was increased in mice treated with nootkatone + DEPs compared with those treated with DEPs or nootkatone + saline. The DNA damage caused by DEPs was prevented by nootkatoone pretreatment. In conclusion, nootkatoone alleviates DEP-induced thrombogenicity and systemic and cardiac oxidative stress and DNA damage, at least partly, through nuclear factor erythroid-derived 2-like 2 and heme oxygenase-1 activation.NEW & NOTEWORTHY Nootkatoone, a sesquiterpenoid found in grapefruit, alleviates the thrombogenicity and systemic and cardiac oxidative stress and DNA damage in mice exposed to diesel exhaust particles. Nootkatone-induced boosting of nuclear factor erythroid-derived 2-like 2 and heme oxygenase-1 levels in the heart of mice exposed to diesel exhaust particles suggests that its protective effect is, at least partly, mediated through nuclear factor erythroid-derived 2-like 2 and heme oxygenase-1 activation.

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