Therapeutic carbon monoxide
Carbon monoxide foam treats intestinal inflammation
Ekaterina Petrova, PCR.news
Inhaling carbon monoxide (CO) is deadly due to its high affinity for hemoglobin. But in small concentrations it acts as a biologically active immunomodulatory agent. Preclinical studies have shown that low concentrations of carbon monoxide reduce inflammation and are able to stimulate tissue regeneration. So, if CO is injected directly into the gastrointestinal tract, it can alleviate the course of mucosal diseases. However, it is difficult to ensure the safe delivery of the appropriate dose into the body, inhalation is fraught with complications.
Scientists from the Massachusetts Institute of Technology and other US research centers have developed a way to deliver CO to the intestine in the form of foam. They were inspired by the achievements of molecular cooking, a scientific discipline that studies the physical and chemical transformations that occur during cooking. Cooks have been creating edible foam for centuries by whipping up a liquid or solid substance with a thickener (for example, fruit puree) or by introducing air or carbon dioxide into it with a siphon.
Researchers have created a family of gas-entrapping materials (GEM) from safe components used in the food industry: xanthan gum (stabilizer), methylcellulose, maltodextrin and corn syrup. With the help of a siphon, they foamed this mixture with carbon monoxide. The time it takes to release the gas can be controlled by changing the concentration of xanthan gum.
In mice, rats and pigs, the authors tested how foam works. They injected it rectally with a syringe with a nozzle. GEM with carbon monoxide weakened inflammation in models of colitis and oxidative tissue damage, and also reduced radiation-induced damage to the intestinal epithelium in rodents.
The researchers also found out whether carbon monoxide can affect other organs, such as the liver. The gas is able to diffuse from the gastrointestinal tract to other parts of the body, so in theory it was possible. To do this, the scientists used a mouse model of acetaminophen overdose (APAP), which causes serious liver damage. It turned out that the gas injected into the lower gastrointestinal tract reaches the liver and significantly reduces inflammation and tissue damage.
Thus, the authors were able to organize an easily modulated delivery of CO into the animal body, and the gas concentrations were high enough for a therapeutic effect in vivo in both rodents and pigs. No side effects could be detected.
Current treatments for colitis and other inflammatory conditions, such as Crohn's disease, are based on immunosuppression and can make the patient more susceptible to infections. Applying foam directly to inflamed tissues can be a safe alternative or supplement to immunosuppressive methods. GEM can also be delivered orally, the authors emphasize.
In addition to foam, scientists have created gels containing carbon monoxide and gas-filled solids similar to Pop Rocks "clicking" candies with carbon dioxide bubbles under pressure. The authors plan to test them in further experiments, as well as to develop foams for human studies.
Article by Li et al. Delivery of therapeutic carbon monoxide by gas-entrapping materials is published in the journal Science Translational Medicine.
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