Maresin-1 Mitigates Doxorubicin-Induced Cardiovascular Injury in Rats By Up-Regulation of Nrf2/HO-1 Signaling Pathway

Background: The use of doxorubicin (DOX), a broad range antitumor antibiotic, has been restricted due to the development of toxicities to important organs, such as the cardiovascular system. Maresin-1 (MaR-1) has strong pro-resolution and anti-inflammatory properties. Objective: To demonstrate the potential underlying mechanisms and cardiovascular protective effect of MaR-1 in DOX-induced CVS damage. Materials and methods: DOX, DOX+MaR-1, and control (10/group) were the three groups into which thirty male albino rats were divided. Assessments were made of the following: cardiac index, cardiac troponin-I (cTnI), cardiac LDH, cardiac CK-MB, serum lipid, cardiac MDA, cardiac SOD, cardiac TNF-α, cardiac IL-6, cardiac IL-10, cardiac Nrf2 gene expression, and cardiac HO-1 gene expression. Furthermore, histological and immunohistochemical examinations of the heart and aorta were carried out. Results: Serum levels of cTnI, LDH, CK-MB, cholesterol, triglycerides, cardiac MDA, TNF-α, IL-6, and cardiac caspase-3 immunoreaction were dramatically elevated than control, while the DOX group's cardiac index value, cardiac SOD, cardiac IL-10, cardiac Nrf2 gene expression, cardiac HO-1 gene expression, and aortic ENOS immunoreaction were significantly lower. MaR-1 significantly reduced the cardiovascular alterations brought on by DOX. Conclusion: By upregulating the cardiac Nrf2/HO-1 pathway and exhibiting anti-inflammatory, antiapoptotic, antioxidant, lipid-lowering, and anti-atherogenic properties, MaR-1 protects the cardiovascular system in DOX rats.