Memantine, an NMDA Receptor Antagonist, Attenuates Doxorubicin-Induced Cardiac Oxidative Stress and Inflammation in...

Breast cancer is the most common cancer among women, and chemotherapy is a key treatment option. Doxorubicin is frequently used for breast cancer but poses a risk of cardiotoxicity. Recently, memantine, an N-Methyl-D-aspartate antagonist, has shown both antitumor and cardioprotective effects.

We conducted a study to examine the combined effects of doxorubicin and memantine on the 4T1 cell line in a breast cancer animal model and to assess memantine's potential in reducing doxorubicin-induced cardiotoxicity in breast cancer model mouse.

The 4T1 cell line was cultured and subsequently inoculated into mice. After that animals were randomly divided into four groups: (1) control, (2) memantine, (3) doxorubicin, and (4) memantine + doxorubicin.

After 30 days, mice were sacrificed, and their lungs, liver, and heart were collected for histological analysis. Myeloperoxidase, Malondialdehyde, and TNF-α levels in cardiac tissues were measured, and the TUNEL test was conducted for breast tumors.

Our results showed that memantine + doxorubicin reduced MDA activity and TNF-α levels in cardiac tissue in comparison to the doxorubicin group. TUNEL test revealed that the memantine + doxorubicin group demonstrated significantly more tumor cell apoptosis than the mice in other groups (P-value < 0.05), although tumor volume reduction was not significantly greater than that in the doxorubicin group.

This study is the first to demonstrate that memantine can enhance the therapeutic efficacy of doxorubicin chemotherapy while also reducing doxorubicin-induced cardiac oxidative stress and inflammation in a breast cancer model.