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However, traditional methods of CO delivery pose complex challenges for daily administration, such as dosing and toxicity. To address these challenges, we developed a novel oral liquid drug product containing CO (HBI\u2010002) that can be easily self\u2010administered by patients with cancer undergoing doxorubicin treatment, resulting in CO being delivered through the upper gastrointestinal tract.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">HBI\u2010002 was tested in a murine model of doxorubicin cardiotoxicity in the presence and absence of lung or breast cancer. The mice received HBI\u2010002 twice daily before doxorubicin administration and experienced increased carboxyhemoglobin levels from a baseline of \u22481% to 7%. Heart tissue from mice treated with HBI\u2010002 had a 6.3\u2010fold increase in CO concentrations and higher expression of the cytoprotective enzyme heme oxygenase\u20101 compared with placebo control. In both acute and chronic doxorubicin toxicity scenarios, HBI\u2010002 protected the heart from cardiotoxic effects, including limiting tissue damage and cardiac dysfunction and improving survival. In addition, HBI\u2010002 did not compromise the efficacy of doxorubicin in reducing tumor volume, but rather enhanced the sensitivity of breast 4T1 cancer cells to doxorubicin while simultaneously protecting cardiac function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">These findings strongly support using HBI\u2010002 as a cardioprotective agent that maintains the therapeutic benefits of doxorubicin cancer treatment while mitigating cardiac damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.123.032067","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T06:19:59Z","timestamp":1714717199000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Beneficial Effects of Oral Carbon Monoxide on Doxorubicin\u2010Induced 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