MDMA causes toxic effects and programmed cell death (apoptosis) in a mouse Leydig cell line (TM3). Treatment with MDMA increased reactive oxygen species (ROS) production and the expression of pro-apoptotic proteins caspase 3, Bax, and p53, while decreasing the anti-apoptotic protein Bcl-2. Pre-treatment with zinc for 24 hours before MDMA exposure significantly reduced ROS production, lowered the number of apoptotic cells, and decreased pro-apoptotic protein expression compared to MDMA alone. Zinc pre-treatment mitigates MDMA-induced oxidative stress and apoptosis in TM3 cells.
MDMA (ecstasy) triggers cell death in mouse Sertoli and Leydig cells by increasing expression of pro-apoptotic genes bax and p53 and decreasing anti-apoptotic bcl-2. Pre-treatment with 8 µM zinc largely prevented these changes: in Leydig cells, bax and p53 mRNA levels returned to control values; in Sertoli cells, bax and bcl-2 levels normalized. Zinc appears to protect against MDMA-induced apoptosis by modulating the interplay among bcl-2, bax, and p53 gene expression in these reproductive cell lines.
MDMA (ecstasy) exposure reduces the viability of cultured Sertoli cells and increases expression of the apoptosis-related gene caspase-3. Pre-treatment with a low concentration of zinc (8 μM) attenuates this effect, lowering caspase-3 mRNA levels and suggesting a protective role against MDMA-induced cell death. The mean caspase-3 mRNA fold change was 3.98 in cells treated with 5 mM MDMA, 0.31 in cells treated with 8 μM zinc alone, and 1.72 in cells pre-treated with zinc before MDMA, compared to untreated controls. Only the MDMA-only group showed a statistically significant difference from controls.