An oral prodrug developed by a team of scientists led by Binghe Wang, a Regent chemistry professor at Georgia State University, delivers carbon monoxide to protect against acute kidney damage, according to a new paper published in Chemical Science.
Although Carbon monoxide Gases (CO) are toxic in large doses, scientists have discovered that they can have beneficial effects in reducing inflammation and protecting cells from injury. Previous studies have shown the protective effects of CO against injuries to the kidneys, lungs, gastrointestinal tract, and liver, among other organs. For the past five years, Wang and his collaborators have worked to design a safe way to deliver CO a human patients by prodrugs: inactive compounds that must undergo a chemical process in the body before releasing the active pharmacological agent.
Wang’s team developed prodrugs that allow oral administration of CO using two common artificial sweeteners: saccharin (a Sweet’N Low ingredient) and acesulfame (a Splenda ingredient), as “carrier” molecules. . They designed the molecules to release CO in the decomposition process, which is triggered by exposure to water. These are the first examples of orally active organic CO prodrugs that use a benign carrier that is approved by the Food and Drug Administration with a proven safety profile.
“It is difficult to supply a gas, let alone a toxic gas, as a therapeutic for patients, and this work represents a major step forward in the development of alternative delivery forms,” said Wang, lead author of the paper and a researcher eminent member of the Georgia Research Alliance. . “We wanted to work with a carrier that had a very well-characterized safety profile, which confers a higher degree of safety that will be safe to use on a pill for human consumption.”
Of the two prodrugs, the scientists tested one, CO-306, to determine the pharmacological efficacy against acute kidney damage. The researchers administered CO-306, which uses saccharin as a carrier molecule, to mice and found that it reduced the biomarkers associated with kidney damage, indicating that it could become a viable therapy. He mouse model they mimicked the mechanisms of kidney tissue damage that occur in patients with extensive muscle damage, sickle cell disease, a common type of malaria, cardiopulmonary bypass surgery, and severe sepsis.
Wang and colleagues at the Georgia State Center for Diagnostic and Therapeutic Medicine, Vanderbilt University, Harvard Medical School, and the University of Mississippi plan to conduct more extensive animal model studies and evaluations. safety on CO-306 before moving on to clinical studies in humans. They also plan to test the effectiveness of CO-306 against other types of organ damage.
Wang says CO-based therapies are particularly promising as a method to reduce the likelihood of organ damage during transplantation and improve the outcomes of transplant patients.
“Science shows that organ exposure to CO gas can help preserve organs and prevent them from deteriorating during the transplant process,” he said. “We now need to show that these prodrugs can have a similar effect.”
Ladie Kimberly De La Cruz et al, Adaptation of decarbonylation chemistry for the development of prodrugs capable of delivering carbon monoxide in vivo using sweeteners as carrier molecules, Chemical Science (2021). DOI: 10.1039 / D1SC02711E
Georgia State University
Citation: Artificial sweeteners allow the delivery of carbon monoxide to treat organ injuries (2021, July 16) recovered on July 17, 2021 at https://medicalxpress.com/news/2021-07-artificial-sweeteners- enable-delivery-carbon.html
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