Tamoxifen inhibits mitochondrial membrane damage caused by disulfiram
Natalia Pavón1, Mabel Buelna-Chontal2, Francisco Correa2
1a Departamento de Farmacología, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F.
Abstract:
In this work, we studied the protective effects of tamoxifen (TAM) on disulfiram (Dis)-induced mitochondrial membrane insult. The results indicate that TAM circumvents the inner membrane leakiness manifested as Ca2+ release, mitochondrial swelling, and collapse of the transmembrane electric gradient. Furthermore, it was found that TAM prevents inactivation of the mitochondrial enzyme aconitase and detachment of cytochrome c from the inner membrane. Interestingly, TAM also inhibited Dis-promoted generation of hydrogen peroxide. Given that TAM is an antioxidant molecule, it is plausible that its protection may be due to the inhibition of Dis-induced oxidative stress.
Insights
Tamoxifen (TAM) protects mitochondria from disulfiram (Dis)-induced damage by preventing inner membrane leakiness and enzyme inactivation. TAM
Area of Science:
- Mitochondrial Biology
- Pharmacology
- Cellular Toxicology
Background:
- Disulfiram (Dis) induces mitochondrial membrane damage.
- This insult involves Ca2+ release, swelling, and loss of membrane potential.
- Oxidative stress is implicated in disulfiram toxicity.
Purpose of the Study:
- To investigate the protective effects of tamoxifen (TAM) against disulfiram-induced mitochondrial injury.
- To elucidate the mechanisms underlying TAM's protective action.
Main Methods:
- Mitochondrial membrane integrity assays
- Enzyme activity measurements (aconitase)
- Cytochrome c release analysis
- Hydrogen peroxide production monitoring
Main Results:
- TAM prevented disulfiram-induced Ca2+ release, mitochondrial swelling, and loss of transmembrane electric gradient.
- TAM inhibited aconitase inactivation and cytochrome c detachment.
- TAM suppressed disulfiram-promoted hydrogen peroxide generation.
Conclusions:
- Tamoxifen exhibits significant protective effects against disulfiram-induced mitochondrial damage.
- TAM's antioxidant properties likely contribute to its protective mechanism by mitigating oxidative stress.
- TAM preserves mitochondrial function and integrity under toxic conditions.
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