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Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats.
J Mol Neurosci. 2016 Oct; 60(2):214-22.JM

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.

Authors+Show Affiliations

Department of Physiology, Medical Faculty, Adıyaman University, Adıyaman, Turkey.Department of Biophysics, Medical Faculty, Suleyman Demirel University, Isparta, Turkey.Department of Biophysics, Medical Faculty, Suleyman Demirel University, Isparta, Turkey.Department of Biophysics, Medical Faculty, Suleyman Demirel University, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr. Neuroscience Research Center, Suleyman Demirel University, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27372663

Citation

Yazğan, Betül, et al. "Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats." Journal of Molecular Neuroscience : MN, vol. 60, no. 2, 2016, pp. 214-22.
Yazğan B, Yazğan Y, Övey İS, et al. Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats. J Mol Neurosci. 2016;60(2):214-22.
Yazğan, B., Yazğan, Y., Övey, İ. S., & Nazıroğlu, M. (2016). Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats. Journal of Molecular Neuroscience : MN, 60(2), 214-22. https://doi.org/10.1007/s12031-016-0785-9
Yazğan B, et al. Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats. J Mol Neurosci. 2016;60(2):214-22. PubMed PMID: 27372663.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats. AU - Yazğan,Betül, AU - Yazğan,Yener, AU - Övey,İshak Suat, AU - Nazıroğlu,Mustafa, Y1 - 2016/07/02/ PY - 2016/04/23/received PY - 2016/06/21/accepted PY - 2016/7/4/entrez PY - 2016/7/4/pubmed PY - 2017/3/24/medline KW - Apoptosis KW - Brain KW - Cytokine KW - Oxidative stress KW - Selective estrogen receptor modulators SP - 214 EP - 22 JF - Journal of molecular neuroscience : MN JO - J Mol Neurosci VL - 60 IS - 2 N2 - 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. SN - 1559-1166 UR - https://www.unboundmedicine.com/medline/citation/27372663/Raloxifene_and_Tamoxifen_Reduce_PARP_Activity_Cytokine_and_Oxidative_Stress_Levels_in_the_Brain_and_Blood_of_Ovariectomized_Rats_ L2 - https://dx.doi.org/10.1007/s12031-016-0785-9 DB - PRIME DP - Unbound Medicine ER -