A University of Rochester Medical Center study looked at the levels of antioxidants versus the amount of smoke exposure in more than 2,000 6 and 18 years old in the 2003-2004 National Health and Nutrition Examination Survey (NHANES). The study, which was presented at the Pediatric Academic Society Meeting in Baltimore, shows that secondhand smoke exposure is associated with lower levels of antioxidants in children.

"We don't know enough yet to say that this group of children need supplements to make up for the antioxidants they're losing, but it's always wise to feed children an abundance of fruits and vegetables high in antioxidants and other healthy nutrients," said Karen Wilson, M.D., M.P.H., a senior instructor of Pediatrics at the University of Rochester Medical Center and the study's author.

Antioxidants are believed to play an important role in protecting the body's cells against free radicals, which can damage cells. Free radicals are produced during many body processes including when we use oxygen and respond to infections. It is not completely understood how antioxidants work together to neutralize free radicals, but scientists continue to discover more antioxidant compounds, including those examined in the study “ vitamins E and C, folate and beta-carotene.

Children's exposure to tobacco smoke was determined by the level of cotinine in their blood (cotinine is a byproduct of metabolizing tobacco smoke). The higher the level of cotinine in a child's blood, the lower the antioxidant level, after controlling for diet and supplements. The study also looked at vitamins that were not antioxidants and found that these compounds did not seem to be reduced with smoke exposure.

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His group studied two separate strains of mice, each carrying a specific genetic alteration that makes them especially prone to develop atherosclerosis. The mice also lacked CHOP, disabling the prodeath branch of the ER stress pathway.

When fed a diet high in fat and cholesterol for 10 weeks, one strain of those CHOP deficient mice with atherosclerosis developed smaller lesions than mice with CHOP, they report. Most importantly, cell death and plaque necrosis dropped by about 50 percent. The second strain of atherosclerotic mice showed essentially the same result.

Despite the fact that evidence had pointed to ER stress and the UPR before, Tabas said the result - and particularly the magnitude of the effect - still came as a considerable surprise.

"The fact that we were able to isolate one gene encoding one protein with such a profound effect on plaque necrosis was a big surprise," he said. That's because there could be many other processes at work, including some that might compensate for CHOP loss.

The findings in mice could have some real implications in the clinic, Tabas added.

"The results of this study, together with recent findings showing expression of CHOP in vulnerable human atherosclerotic plaques, suggest that the CHOP pathway may be a potential therapeutic target related to the formation of dangerous atheromata," the researchers concluded. "In particular, it will be interesting to determine whether so-called chemical chaperones, which have been successfully used in other animal models of UPR-associated diseases, have a beneficial effect on advanced atherosclerotic lesion progression."

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