Effect of plastoquinone derivative 10-(6′-Plastoquinonyl) decyltriphenylphosphonium (SkQ1) on estrous cycle and 17β-estradiol level in rats

Background Targeting negatively charged mitochondria is often achieved using triphenylphosphonium (TPP) cations. These cationic vehicles may possess biological activity, and a docking study indicates that TPP-moieties may act as modulators of signaling through the estrogen receptor α (ERα). Moreover, in vivo and in vitro experiments revealed the estrogen-like effects of TPP-based compounds. Here, we tested the hypothesis that TPP-based compounds regulate the activity of ERα. Methods We used ERa-positive and ERα-negative human breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231, respectively). Cell proliferation was measured using a resazurin cell growth assay and a real-time cell analyzer assay. Cell cycle progression was analyzed using flow cytometry. Real-time PCR was used to assess mRNA expression of endogenous estrogen-responsive genes. Luciferase activity was measured to evaluate transcription driven by estrogen-responsive promoters in cells transfected with an estrogen response element (ERE)3-luciferase expression vector. Results The TPP-based molecules SkQ1 and C12TPP, as well as the rhodamine-based SkQR1, did not increase the proliferation or alter the cell cycle progression of MCF-7 cells. In contrast, 17β estradiol increased the proliferation of MCF-7 cells and the proportion of cells in the S/G2/M-phases of the cell cycle. TPP-based compounds did not affect the induction of transcription of an ERE-luciferase expression vector in vitro, and SkQ1 did not alter the levels of expression of estrogen-dependent genes encoding GREB1, TFF1, COX6, and IGFBP4. Conclusion TPP-based compounds do not possess properties typical of ERα agonists.

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“…• SkQ1 consumption by female rats prolongs proestrus duration, typical of E2 (Chistyakov et al, 2012).…”

Section: Introductionmentioning

confidence: 96%

Mitochondria-targeted triphenylphosphonium-based compounds do not affect estrogen receptor α

Zinovkina

Galivondzhyan

Prikhodko

et al. 2020

PeerJ

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Reproductive parameters of female Wistar rats treated with methylphenidate during development

Montagnini

Silveira

Pierone

et al. 2016

Physiology & Behavior

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Methylphenidate (MPH), a psychoactive agent that acts mainly by blocking the uptake of dopamine, is the main drug used to treat Attention Deficit Hyperactivity Disorder in children and adolescents. During development, important changes in brain architecture and plasticity occur, these changes, sensitive to exposure to stimulant drugs, are important in the control of GnRH secretion, influencing the release of sex hormones throughout the ovarian cycle. This study investigated the effects of repeated treatment with MPH during development on reproductive parameters of adult female rats. Wistar rats received MPH 2.5mg/kg, MPH 5.0mg/kg, or tap water (gavage) from postnatal day (PND) 21 to PND 60. From PND 75, one subgroup of females was selected for evaluation of estrous cycle, estradiol levels, weight of sexual organs, and histomorphological analysis of ovary follicles and uterus. In another subgroup, the sexual and maternal behaviors were evaluated at PND 90 and on lactational day 5, respectively. No significant alterations were observed in the MPH groups. This study demonstrated that repeated administration of MPH during the period corresponding to childhood to early adulthood does not interfere in the reproductive function of female rats in adulthood.

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Investigation of the potential effects of triclosan as an endocrine disruptor in female rats: Uterotrophic assay and two-generation study

et al. 2018

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Effect of plastoquinone derivative 10-(6′-Plastoquinonyl) decyltriphenylphosphonium (SkQ1) on estrous cycle and 17β-estradiol level in rats

Cited by 3 publications

References 9 publications

Mitochondria-targeted triphenylphosphonium-based compounds do not affect estrogen receptor α

Mitochondria-targeted triphenylphosphonium-based compounds do not affect estrogen receptor α

Reproductive parameters of female Wistar rats treated with methylphenidate during development

Investigation of the potential effects of triclosan as an endocrine disruptor in female rats: Uterotrophic assay and two-generation study

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