Mitigation of Negative Effects of Melphalan on Cardiomyocytes

Mitigation of Negative Effects of Melphalan on Cardiomyocytes with N-acetyl-L-cysteine (NAC) Treatment

Application

NAC (N-acetyl-L-cystine) as an antioxidant to reduce chemotherapy induced oxidative stress and cardiotoxicity.

Key Benefits

Mitigates cardiotoxic side effects of alkylating agent, melphalan in human cardiomyocytes.

Market Summary

Melphalan is a chemotherapeutic commonly used to treat various cancers including multiple myeloma, leukemia, and ovarian cancer and is also administered in children receiving bone marrow transplants. Unfortunately, melphalan negatively affects cardiomyocytes (heart cells) which can cause cardiac diseases. Affected patients have an increased likelihood of ICU admission and longer hospital stays. Researchers at Emory University have found a method to mitigate the negative effects of melphalan on cardiomyocytes with N-acetyl-L-cysteine (NAC) treatment.

Technical Summary

Researchers have developed a novel antioxidant to reduce the chemotherapy induced oxidative stress and cardiotoxicity using N-acetyl-L-cystine (NAC). NAC is an antioxidant mostly used as a dietary supplement available at health food stores, but it is sometimes utilized to treat acetaminophen overdoses. Melphalan is a chemotherapeutic commonly used to treat a variety of cancers, however it has been shown to negatively affect heart cells which can lead to cardiac diseases. The researchers demonstrated that melphalan acts on heart cells through oxidative stress, p53, and TGβ pathways. Under melphalan treatment researchers observed NAC mitigating cell loss and mitochondrial reactive oxygen species production in hiPSC-CMs, furthermore NAC was observed to ameliorate the alteration of heart cell beating indexes caused by melphalan.

Publication: Melphalan Induces Cardiotoxicity Through Oxidative Stress in Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells Stem Cell Res Ther. 2020; 11: 470