Cigarette smoking causes emphysema, a disease characterized by serious structural damage to lung tissues. Smoke introduces oxidizing agents into the lung that activate inflammation and induce over-production of nitric oxide in lung tissues, leading to emphysema. A new paper published in PNAS shows that tobacco smoke exposure can be partly counteracted by doses of vitamin C and another drug, a selective nitric oxide synthase inhibitor. In other words, vitamin C could provide some protection against smoking-related lung damage.

The authors of this study have previously shown that cigarette smoke damages lung proteins via oxidation, but they hadn’t fully characterized the mechanisms involved. To further explore tobacco-induced lung damage, the researchers worked with a guinea pig model, exposing some animals to cigarette smoke and comparing them to controls. They found that exposed guinea pigs showed extensive breakdown of major lung structural proteins and that this damage helped foster emphysema.

The experiments also showed that smoke-exposed lungs had altered expression of nitric oxide synthase proteins, which resulted in increased production of nitric oxide in these tissues. Cigarette smoke exposure was directly linked to the presence of nitric oxide in exposed tissues and those tissues’ oxidative damage.

Nitric oxide is a signaling molecule that, among other functions, helps induce inflammation. So the researchers treated some smoke-damaged lungs with anti-inflammatories. They found that these treatments didn’t block the damage to lung proteins. Since oxidation was the problem, the researchers next turned to anti-oxidants—specifically, to vitamin C, which is a strong, water-soluble anti-oxidant.

Smoke-exposed animals were given oral vitamin C supplements in combination with a selective nitric oxide synthase inhibitor delivered directly into the lungs. This reduced the smoke-induced lung damage by between 48 and 78 percent. The effects of the vitamin C and nitric oxide synthase inhibitor together were significantly higher than the protective effects that either treatment achieved individually. However, even Vitamin C alone provided protection against the breakdown of elastin, a protein that helps structurally support lung tissue.

Treatment with vitamin C and the nitric oxide synthase inhibitor decreased the expression of nitric oxide synthases to levels comparable to the control animals. This means that the joint treatment returned the expression of these proteins to almost the same levels seen in tissues that haven’t been exposed to cigarette smoke. In fact, treated animals had a decrease in whole-lung nitric oxide generation from between 59 and 86 percent.

The results of these experiments indicate it’s possible to at least partly protect lung tissues against oxidative damage due to cigarette smoke exposure and suppress the inflammatory response that follows.

Over the last several years and decades, there have been various social, regulatory, and public health programs to reduce the practice of cigarette smoking in the US, but smoking remains common. Finding a way to limit the damage among people who continue to smoke can therefore be valuable. But nitric oxide signaling is involved in a large number of processes, so it’s not clear whether perpetually inhibiting it in the lungs is safe. And it’s important to recognize that emphysema is just one of a large number of diseases caused by smoking.

PNAS, 2016. DOI: 10.1073/pnas.1600056113 (About DOIs).