Mitochondria from distinct tissues are differently affected by 17β-estradiol and tamoxifen

This study was aimed to analyse and compare the bioenergetics and oxidative status of mitochondria isolated from liver, heart and brain of ovariectomized rat females treated with 17β-estradiol (E2) and/or tamoxifen (TAM). E2 and/or TAM did not alter significantly the respiratory chain of the three types of mitochondria. However, TAM significantly decreased the phosphorylation efficiency of liver mitochondria while E2 significantly decreased the phosphorylation efficiency of heart mitochondria. E2 also significantly decreased the capacity of heart and liver mitochondria to accumulate Ca2+ this effect being attenuated in liver mitochondria isolated from E2 + TAM-treated rat females. TAM treatment increased the ratio of glutathione to glutathione disulfide (GSH/GSSG) of liver mitochondria. Brain mitochondria from TAM- and E2 + TAM-treated females showed a significantly lower GSH/GSSG ratio. However, heart mitochondria from TAM- and E2 + TAM-treated females presented a significant decrease in GSSG and an increase in GSH/GSSG ratio. Thiobarbituric acid reactive substances levels were significantly decreased in liver mitochondria isolated from E2 + TAM-treated females. Finally, E2 and/or TAM treatment significantly decreased the levels of hydrogen peroxide produced by brain mitochondria energized with glutamate/malate. These results indicate that E2 and/or TAM have tissue-specific effects suggesting that TAM and hormonal replacement therapies may have some side effects that should be carefully considered.

Research highlights▶ The impact of 17β-estradiol and/or tamoxifen on mitochondria function is tissue-specific. ▶ 17β-Estradiol has beneficial effects on brain mitochondria. ▶ 17β-Estradiol has deleterious effects in liver and heart mitochondria being these effects more pronounced in heart mitochondria. ▶ Tamoxifen may interfere with liver and brain mitochondria. ▶ Tamoxifen and hormonal replacement therapies may have some side effects that should be carefully considered.