Carbon monoxide protects lung cells against oxygen-induced damage

Jan 18, 2007

Researchers at the University of Pittsburgh have demonstrated that low-dose carbon monoxide administered in conjunction with oxygen therapy markedly inhibits oxygen-induced damage to lung cells. These findings, being reported in the Jan. 19 issue of the Journal of Biological Chemistry, have significant implications for the treatment of acute respiratory distress syndrome, or ARDS, according to the study's authors.

ARDS is a life-threatening medical condition in which patients experience severe shortness of breath and oxygen starvation. Although ARDS often occurs in people who have lung disease, even people with normal lungs can develop the condition as the result of severe trauma or an infection. Without prompt treatment, the oxygen deprivation resulting from ARDS can be lethal. Even with appropriate treatment, however, about 30 to 40 percent of all people with severe ARDS die from the condition. In fact, it is the number one killer of patients in intensive care unit facilities in the United States.

Treatment for ARDS primarily involves hooking the patient up to a mechanical ventilator and giving them almost pure oxygen (95 percent oxygen and 5 percent carbon dioxide). However, recent studies in animals have shown that prolonged exposure to an elevated level of oxygen, or hyperoxia, can cause long-term lung injury that resembles ARDS.

Based on previous research showing that low-dose carbon monoxide (CO) has potent anti-inflammatory effects in a number of tissues, the Pitt researchers cultured lung cells from mice in a medium with a high concentration of oxygen, with and without low levels of CO. They then monitored the cells for hyperoxia-induced toxicity.

The presence of CO in the hyperoxic medium significantly inhibited the destruction of lung cells as well as the production of molecules in the cells that are known to induce cell suicide, or apoptosis. In contrast, more than half of the mouse lung cells incubated in hyperoxic media without CO died within 72 hours--compared to about 25 percent of the CO-treated cells--and they produced high levels of apoptotic molecules.

According to the investigators, these results suggest that CO may expand the currently limited therapeutic options for treating ARDS.

"Giving ARDS patients almost pure oxygen over a prolonged period may be a double-edged sword," said lead investigator Augustine Choi, M.D., professor of medicine and the chief of the division of pulmonary, allergy and critical care medicine at the University of Pittsburgh School of Medicine. "It saves their life in the short term, but long-term exposure appears to cause significant damage to many cell types including the epithelial and endothelial cells of the lung. However, by administering oxygen mixed with a very small amount of carbon monoxide, we may be able to significantly reduce such oxygen-associated damage and cell death."

Although high concentrations of carbon monoxide are toxic, Dr. Choi's laboratory and others have demonstrated that CO can be therapeutic at very low concentrations. Last year, Dr. Choi's group conducted a study with researchers at the National Institutes of Health, which demonstrated that administering small amounts of inhaled CO to normal individuals was not damaging to their health. They now are preparing to submit an application to the U.S. Food and Drug Administration to test whether CO administered to human patients with ARDS is beneficial.

Source: University of Pittsburgh Medical Center

Explore further: Scientists discover new clues to how weight loss is regulated

add to favorites email to friend print save as pdf

Related Stories

Tuning light to kill deep cancer tumors

Oct 15, 2014

An international group of scientists led by Gang Han, PhD, at the University of Massachusetts Medical School, has combined a new type of nanoparticle with an FDA-approved photodynamic therapy to effectively kill deep-set ...

New material steals oxygen from the air

Sep 30, 2014

Researchers from the University of Southern Denmark have synthesized crystalline materials that can bind and store oxygen in high concentrations. Just one spoon of the substance is enough to absorb all the ...

Fine tuning an old-school chemotherapy drug

May 05, 2014

First approved by the FDA in the 1970s, the chemotherapy drug cisplatin and its relative carboplatin remain mainstays of treatment for lung, head and neck, testicular and ovarian cancer. However, cisplatin's ...

Nickel nanoparticles may contribute to lung cancer

Aug 23, 2011

All the excitement about nanotechnology comes down to this: Structures of materials at the scale of billionths of a meter take on unusual properties. Technologists often focus on the happier among these newfound capabilities, ...

Malaria: Blood cells behaving badly

Jun 10, 2014

All the billions of flat, biconcave disks in our body known as red blood cells (or erythrocytes) make three basic, tumbling-treadmill-type motions when they wend their way through the body's bloodstream ferrying ...

Recommended for you

Team finds key signaling pathway in cause of preeclampsia

4 hours ago

A team of researchers led by a Wayne State University School of Medicine associate professor of obstetrics and gynecology has published findings that provide novel insight into the cause of preeclampsia, the leading cause ...

Rapid test to diagnose severe sepsis

8 hours ago

A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

User comments : 0