Azilsartan improves doxorubicin-induced cardiotoxicity via inhibiting oxidative stress, proinflammatory pathway, and apoptosis.

Azilsartan, a known angiotensin receptor blocker, has shown potential in reducing 24-hour blood pressure and may have protective effects against cardiac complications. Increased oxidative stress in cardiac tissue is directly related to the cardiac complications of doxorubicin. This study investigated whether azilsartan could mitigate doxorubicin-induced cardiotoxicity. We divided 28 male rats into four groups: the control group receiving a standard diet and water, the vehicle group given DMSO orally for two weeks, doxorubicin group receiving 2.5 mg/kg of doxorubicin three times a week for two weeks, and azilsartan group treated with 5 mg/kg/day of azilsartan orally and doxorubicin. Doxorubicin-induced cardiotoxicity was evidenced by a significant increase in TNF-α, IL-1β, MDA, and caspase-3 levels and significantly decreased TAC and Bcl-2 levels in the cardiac tissues of treated rats compared to the DMSO and control groups. Azilsartan significantly decreased doxorubicin-induced cardiotoxicity, as evidenced by a decline in serum levels of both TNF-α and IL-1β. Additionally, MDA significantly decreased in the cardiac tissue, although TAC was significantly increased when comparing the azilsartan group to the group receiving doxorubicin-only. These results suggest that azilsartan effectively reduced doxorubicin-induced cardiotoxicity, likely by mitigating apoptosis, inflammation, and oxidative stress in cardiac tissues.