Along with the afore mentioned estradiol-induced reduction in peroxide production and mitochondrial DNA damage, there is an increase in mitochondrial glutathione levels that is coupled with significant increases in expression of glutathione
peroxidase and manganese superoxide dismutase RNA and protein [18]. Thus through modulation of antioxidant enzyme expression and activity, estradiol can prevent the mitochondrial spiral, by blocking further increases in reactive oxygen species production and mitochondrial damage.