Curcumin Moderates the Health Effects of Diesel Exhaust

The majority of the ground transporation in the United States runs on diesel fuel. It powers most of the fleet of large vehicles that travel around Wisconsin and across country moving products and people. My family uses diesel fuel in all the large tractors that plant and harvest the 1,200+ acres of crops on the farm as well in the semitrailer that hauls the final product to market. Diesel also fuels a small portion of the passenger vehicles that people drive every day in the United States, including the car that is my main mode of transport. However, exposure to diesel exhaust can have negative effects on human health, and recent reports have found an increased risk of lung cancer. While these studies documented heavy exposure levels (miners underground with diesel generators), people still wonder about the effect of exposure when behind a truck spewing dark exhaust. A recent PLoS ONE article examined the effect of diesel exhaust particles on mouse cardiovascular systems and how treating with curcumin attenuated the negative effects.

In an earlier publication, Nemmar et al. had shown a single exposure to diesel exhaust particles (DEP) activated the inflammatory reponse in the lungs and induced thrombosis (formation of blot clots) in mouse brain. They wanted to see if there were effects on blood coagulation and airway inflammation with multiple exposures to DEP and then see if curcumin, the yellow pigment in turmeric that has been shown to inhibit cigarette-smoke-induced lung inflammation in mice, could reverse the negative DEP effects. The mice were exposed to DEP not by enclosure in a chamber and breathing DEP but instead were sedated and a liquid suspension of DEP in saline was applied to their tracheas. To control for effects of the treatment method, some of the mice were exposed to saline alone. The mice were exposed to DEP or saline with or without curcumin every other day for six days for a total of four exposures. On day eight, they assessed various pulmonary and respiratory markers, including blood pressure taken using a tail cuff and airway hyperreactivity response after exposure to an aerosol chemical that constricts the bronchial passages, a diagnostic test for asthma.

Blood and lung washings were taken from the mice and used to test for inflammation. For these mice, DEP increased infiltration of lymphocytes and polymorphonuclear neutrophils, cells from the immune system, in the lungs and increased expression of TNFα, a cytokine that is present during inflammation. Curcumin treatment alone did not affect cell numbers or cytokine levels (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNFα]) but, when used with DEP exposure reduced the cell numbers and cytokine levels to saline control, reversing the effect of DEP.

The trend of curcumin reversing the effects of DEP continued in other tests. The airway hyperactivity test showed DEP treatment increased hyperactivity as the dose increased; curcumin reversed these effects to control levels and did not affect airway hyperactivity when used alone. Blood pressure increased when mice were exposed to DEP; curcumin cotreatment reduced blood pressure and did not affect blood pressure when used alone. Plasma levels of inflammatory cytokines (IL-6, TNFα and C-reactive protein [CRP]) were also assessed. TNFα and CRP were elevated by DEP treatment; curcumin cotreatment reduced levels to those seen in control mice while curcumin alone had no effect on any of these markers.

As for the effect on blood coagulation, exposure to DEP reduced the number of platelets while curcumin cotreatment improved numbers and had no significant increase of platelets when used alone. Testing how long it took for blood flow to stop in brain arterioles showed DEP exposure reduced the time blood took to clot while curcumin cotreatment was able to increase the time. Curcumin alone had no effect on blood coagulation time. Three other molecules involved with clot formation, D-dimer, plasminogen activator inhibitor 1 (PAI-1) and von Willebrand factor (vWF), were also assessed, and the researchers found that levels of D-dimer and PAI-1 were increased in the presence of DEP (vWF changes were not significant). Curcumin cotreatment was able to moderate some of this increase.

This research showed measurable changes in mice exposed to DEP. The molecule Nemmar et al. selected to possibly moderate the changes, curcumin, did prove its worth. The molecule alone did not change the measurements but when used in mice exposed to DEP was able to moderately or completely reverse the effects, depending on what was assessed. The effects in a whole animal versus cultured cells are generally considered closer to real-world effects. However, the experiment did not use inhaled particles, which more closely mimics the mode of exposure most mammals in the real world receive, and effects seen in mice do not necessarily translate to humans. The beneficial effect of curcumin was reproducible among the measurements and shows enough promise it warrants additional testing. Until I can take a pill to reverse the effects of DEP on my cardiovascular system, I will try to keep my distance from the tailpipes of diesel-fueled vehicles.

Reference
Nemmar, A., Subramaniyan, D. and Ali, B.H. (2012). Protective effect of curcumin on pulmonary and cardiovascular effects induced by repeated exposure to diesel exhaust particles in mice. PLoS ONE, 7 (6) PMID: 22745783

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Sara Klink

Scientific Communication Specialist at Promega Corporation
Sara is a native Wisconsinite who grew up on a fifth-generation dairy farm and decided she wanted to be a scientist at age 12. She was educated at the University of Wisconsin—Parkside, where she earned a B.S. in Biology and a Master’s degree in Molecular Biology before earning her second Master’s degree in Oncology at the University of Wisconsin—Madison. She has worked for Promega Corporation for more than 10 years, first as a Technical Services Scientist, currently as a Scientific Communication Specialist. Sara is camera shy but may succumb to peer pressure and post an image.

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