Cigarette smoking causes emphysema, a disease characterized by severe structural damage to lung tissue. Smoke introduces oxidants into the lungs that activate inflammation and cause an overproduction of nitric oxide in lung tissues, leading to emphysema. A new article published in PNAS shows that exposure to tobacco smoke can be counteracted in part by doses of vitamin C and another drug, a selective nitric oxide synthase inhibitor. In other words, vitamin C might offer some protection against smoking-related lung damage.
The authors of this study had previously shown that cigarette smoke damages lung proteins via oxidation, but they had not fully characterized the mechanisms involved. To further investigate lung damage caused by tobacco, the researchers worked with a guinea pig model, exposing some animals to cigarette smoke and comparing them to control animals. They found that exposed guinea pigs showed extensive degradation of key lung structural proteins and that this damage promoted emphysema.
The experiments also showed that smoke-exposed lungs had altered expression of nitric oxide synthase proteins, resulting in increased nitric oxide production in these tissues. Exposure to cigarette smoke was directly linked to the presence of nitric oxide in exposed tissues and the oxidative damage of those tissues.
Nitric oxide is a signaling molecule that, among other things, helps to induce inflammation. So the researchers treated some smoke-damaged lungs with anti-inflammatories. They found that these treatments did not block damage to lung proteins. Since oxidation was the problem, the researchers next turned to antioxidants, specifically vitamin C, a strong, water-soluble antioxidant.
Smoke-exposed animals received oral vitamin C supplements in combination with a selective nitric oxide synthase inhibitor administered directly into the lungs. This reduced smoke-induced lung damage by 48 to 78 percent. The effects of the vitamin C and nitric oxide synthase inhibitor together were significantly higher than the protective effects achieved by either treatment alone. But even vitamin C alone provided protection against the breakdown of elastin, a protein that structurally supports lung tissue.
Treatment with vitamin C and the nitric oxide synthase inhibitor reduced the expression of nitric oxide synthases to levels comparable to those of the control animals. This means that the co-treatment reduced the expression of these proteins to almost the same levels as in tissues not exposed to cigarette smoke. In fact, treated animals had a decrease in nitric oxide formation in the entire lung of between 59 and 86 percent.
The results of these experiments indicate that it is possible to at least partially protect lung tissue from oxidative damage resulting from exposure to cigarette smoke and to suppress the inflammatory response that follows.
In recent years and decades, there have been several social, regulatory, and public health programs to reduce cigarette smoking in the US, but smoking remains common. It may therefore be valuable to find a way to limit the harm in people who continue to smoke. But nitric oxide signaling is involved in a myriad of processes, so it’s not clear whether inhibiting it continuously in the lungs is safe. And it’s important to recognize that emphysema is just one of many diseases caused by smoking.
PNAS2016. DOI: 10.1073/pnas.1600056113 (About DOIs).