Abstract
Doxorubicin is a common chemotherapy treatment with numerous negative ramifications of use such as nephropathy and radiation-induced cardiotoxicity. Doxorubicin has been shown to cause overexpression of proinflammatory cytokines including MCP-1 and IL-1β via activation of the NF-κB pathway. Furthermore, apoptosis marked by dysregulation of the Bax/Bcl-2 ratio and oxidative stress and the production of reactive oxygen species (ROS) are also exacerbated by doxorubicin administration. Teneligliptin is part of the wider dipeptidyl peptidase-4 (DPP-4) inhibitor family which has until recently been almost exclusively used to treat type 2 diabetes mellitus. DPP-4 inhibitors such as teneligliptin control the overexpression of glucagon-like peptidase 1 (GLP-1) which has the downstream effects of general insulin resistance and high blood sugar levels. Our findings indicate a significant protective effect of teneligliptin against the aftereffects of doxorubicin as a chemotherapy treatment. This protective effect includes but is not limited to the reduction of inflammation and the mitigation of dysregulated apoptosis, as evidenced by reduced expression of IL-1β and MCP-1, inhibition of NF-κB activation, and improvement of the Bax/Bcl-2 ratio. The aim of the present study was to establish teneligliptin as a potentially useful agent for the treatment of radiation-induced cardiotoxicity, and our findings support this notion.