Carbon monoxide counteracts one side-effect of an anti-c...( Doxorubicin (DOX) is a red-colored a...),Health

Doxorubicin (DOX) is a red-colored anticancer drug that carries serious side effects for the heart, including cardiac muscle deterioration (cardiomyopathy) and scar tissue accumulation in the heart (fibrosis). These cardio-toxic effects are due to inhibition by DOX of mitochondrial biogenesis, a term used to describe cellular energy generation. In a new study by Claude Piantadosi and his colleagues at Duke University Medical Center, mitochondrial biogenesis was recovered in DOX-treated rodents by either inhalation of carbon monoxide (CO) or overexpression of the protein HO-1.

Mitochondrial biogenesis is known to depend on the presence of CO and HO, which promote energy production and defend the cell from injury. In mice treated with DOX, mitochondrial biogenesis in the heart was suppressed, resulting in heart cell death, thinning and dilation of the heart wall, and fibrosis. However, periodic inhalation of CO by DOX-treated mice restored mitochondrial biogenesis and averted cardiomyopathy. Likewise, overexpression of HO-1 in DOX-treated rat cardiac cells reduced mitochondrial DNA damage and subsequent cell death. The authors therefore suggested that protecting mitochondrial biogenesis in cancer patients treated with DOX might reduce the cardio-toxic side effects of the drug.

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