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Zoledronic Acid, Bevacizumab and Dexamethasone-Induced Apoptosis, Mitochondrial Oxidative Stress, and Calcium Signaling Are Decreased in Human Osteoblast-Like Cell Line by Selenium Treatment

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Abstract

Increased intracellular free calcium ion (Ca2+) concentration induces excessive oxidative stress and apoptosis. Medical procedures such as zoledronic acid (Zol), bevacizumab (Bev), and dexamethasone (Dex) are usually used in the treatment of bone diseases (osteoporosis, Paget’s disease, etc.) and to prevent metastasis in the bone although the procedures induce osteonecrosis of the jaw through excessive production of reactive oxygen species (ROS). Recently, we observed regulator roles of selenium (Se) on apoptosis and Ca2+ entry through transient receptor potential vanilloid 1 (TRPV1) channels in the cancer cell lines. Therefore, Se may modulate Zol, Bev, and Dex-induced oxidative stress and apoptosis through regulation of TRPV1 channel. In the current study, we investigated the protective effects of Se on apoptosis and oxidative stress through TRPV1 in Zol, Bev, and Dex-induced osteoblast-like cell line. We used human osteoblast-like cell line (Saos-2), and the cells were divided into 12 groups as control, Zol, Bev, Dex, Se, Zol+Se, Bev+Se, Dex+Se, Zol+Dex, Zol+Dex+Se, Zol+Bev, and Zol+Bev+Se which were incubated with drugs (Zol, Bev, Dex, and Se) for 24 h. The cytosolic free Ca2+ concentration was increased by Zol, Bev, Dex, Zol+Bev, and Zol+Dex, although it was reduced by Se treatment. However, Zol, Bev, and Dex-induced increase in apoptosis, caspase 3, caspase 9, poly (ADP-ribose) polymerase 1 expression levels, and intracellular ROS production values in the cells were decreased by Se treatments. In conclusion, we observed that Zol, Bev, and Dex-induced apoptosis, mitochondrial oxidative stress, and calcium signaling are decreased in human osteoblast-like cell line by the Se treatment. Our findings may be relevant to the etiology and treatment of Zol, Bev, and Dex-induced osteonecrosis by Se.

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Acknowledgments

The abstract of the study as poster presentation was published in the ACBID 10th International Congress, held 11 and 15 May 2016 in Antalya, Turkey (www.acbid.org). The study was supported by Scientific Project Unit of SDU (Protocol No: 4475-ÖYP-D2-15 and Protocol No: ÖYP05259-DR-12). All authors approved the final manuscript.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Suleyman Demirel University, Isparta, Turkey

    Tayfun Yazıcı & Gülperi Koçer

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

    Mustafa Nazıroğlu

  3. Department of Neuroscience, Institute of Health Sciences, Suleyman Demirel University, Isparta, Turkey

    Mustafa Nazıroğlu

  4. Department of Biophysics, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey

    Mustafa Nazıroğlu & Ahmi Öz

  5. Department of Physiology, Faculty of Medicine, Alanya Alaaddin Keykubat University, Alanya, Turkey

    İshak Suat Övey

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  1. Tayfun Yazıcı
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Contributions

MN and TY formulated the present hypothesis and were responsible for writing the report. TY was responsible for cell culture experiments. SÖ and AÖ were responsible for cytosolic Ca2+ release analyses. GK was made critical revision for the manuscript. The authors wish to thank the authors thank Muhammet Şahin, (Neuroscience Research Center, SDU, Isparta, Turkey) for helping with plate reader analyses.

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Correspondence to Tayfun Yazıcı.

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Yazıcı, T., Koçer, G., Nazıroğlu, M. et al. Zoledronic Acid, Bevacizumab and Dexamethasone-Induced Apoptosis, Mitochondrial Oxidative Stress, and Calcium Signaling Are Decreased in Human Osteoblast-Like Cell Line by Selenium Treatment. Biol Trace Elem Res 184, 358–368 (2018). https://doi.org/10.1007/s12011-017-1187-8

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