Background: The emergence of toxicities to vital organs, including the heart, has limited the use of the broad-spectrum antitumor drug doxorubicin (DOX). Sitagliptin (STG) offers a number of defensive advantages. Objective: This study aimed to illustrate the possible underlying processes and cardioprotective impact of STG in cardiotoxicity caused by DOX. Material and methods: DOX, DOX+STG, and control (10/group) were the three groups into which thirty male albino rats were divided. Cardiac index, serum cTnI, serum LDH, serum CK-MB, cardiac MDA, cardiac SOD, cardiac TNF-α, cardiac IL-6, cardiac IL-10, cardiac NF-kB gene expression and cardiac TLR4 gene expression. Furthermore, immunohistochemical and cardiac histology studies were carried out. Results: There was dramatically elevated serum cTnI, serum LDH, serum CK-MB, cardiac MDA, cardiac TNF-α, cardiac IL-6 in addition to cardiac NF-kB and cardiac TLR4 immunoreaction and gene expression with substantial decline in cardiac index value, cardiac SOD and cardiac IL-10 of DOX group compared to control. STG dramatically ameliorated DOX induced cardiac changes. Conclusion: STG offered cardioprotection in DOX induced cardiotoxicity by downregulating the cardiac TLR4/NF-kB pathway, anti-inflammatory and antioxidant functions.
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