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Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats

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Abstract

It is well known that 17β-estradiol (E2) has an antioxidant role on neurological systems in the brain. Raloxifene (RLX) and tamoxifen (TMX) are selective estrogen receptor modulators. An E2 deficiency stimulates mitochondrial functions for promoting apoptosis and increasing reactive oxygen species (ROS) production. However, RLX and TMX may reduce the mitochondrial ROS production via their antioxidant properties in the brain and erythrocytes of ovariectomized (OVX) rats. We aimed to investigate the effects of E2, RLX, and TMX on oxidative stress, apoptosis, and cytokine production in the brain and erythrocytes of OVX rats.

Forty female rats were divided into five groups. The first group was used as a control group. The second group was the OVX group. The third, fourth, and fifth groups were OVX + E2, OVX + TMX, and OVX + RLX groups, respectively. E2, TMX, and RLX were given subcutaneously to the OVX + E2 and OVX + TMX, OVX + RLX groups for 14 days after the ovariectomy respectively.

While brain and erythrocyte lipid peroxidation levels were high in the OVX group, they were low in the OVX + E2, OVX + RLX, and OVX + TMX groups. OVX + E2, OVX + RLX, and OVX + TMX treatments increased the lowered glutathione peroxidase activity in erythrocytes and the brain and reduced glutathione and vitamin E concentrations in the brain. β-carotene and vitamin A concentrations in the brain and TNF-α and interleukin (IL)-1β levels in the plasma of the five groups were not significantly changed by the treatments. However, increased plasma IL-4 levels and Western blot results for brain poly (ADP-ribose) polymerase (PARP) in the OVX groups were decreased by E2, TMX, and RLX treatments, although proapoptotic procaspase 3 and 9 activities were increased by the treatments.

In conclusion, we observed that E2, RLX, and TMX administrations were beneficial on oxidative stress, inflammation, and PARP levels in the serum and brain of OVX rats by modulating antioxidant systems, DNA damage, and cytokine production.

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Abbreviations

E2:

17β-estradiol

GSH:

Reduced glutathione

GSH-Px:

Glutathione peroxidase

LP:

Lipid peroxidation

MDA:

Malondialdehyde

PARP:

Poly (ADP-ribose) polymerase

PARP:

Poly (ADP-ribose) polymerase

PUFAs:

Polyunsaturated fatty acids

RLX:

Raloxifene

ROS:

Reactive oxygen species

SERMs:

Selective estrogen receptor modulators

SOD:

Superoxide dismutase

TMX:

Tamoxifen

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Acknowledgments

The abstract of the study was submitted to the 6th World Congress of Oxidative Stress, Calcium Signaling and TRP Channels, held 24 and 27 May 2016 in Isparta, Turkey (www.cmos.org.tr).

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Authors and Affiliations

  1. Department of Physiology, Medical Faculty, Adıyaman University, Adıyaman, Turkey

    Betül Yazğan

  2. Department of Biophysics, Medical Faculty, Suleyman Demirel University, Isparta, Turkey

    Yener Yazğan, İshak Suat Övey & Mustafa Nazıroğlu

  3. Neuroscience Research Center, Suleyman Demirel University, Isparta, Turkey

    Mustafa Nazıroğlu

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  1. Betül Yazğan
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  2. Yener Yazğan
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  4. Mustafa Nazıroğlu
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Correspondence to Mustafa Nazıroğlu.

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There is no financial disclosure for the current study.

Authorship contributions

MN formulated the hypothesis and was responsible for writing the report. İSÖ was responsible for the animal experiments. BY and YY were responsible from the cytokine, lipid peroxidation, and antioxidant analyses.

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The authors declare that they have no conflicts of interest.

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Yazğan, B., Yazğan, Y., Övey, İ.S. et al. Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats. J Mol Neurosci 60, 214–222 (2016). https://doi.org/10.1007/s12031-016-0785-9

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  • DOI: https://doi.org/10.1007/s12031-016-0785-9

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