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Article

Bicalutamide Elicits Renal Damage by Causing Mitochondrial Dysfunction via ROS Damage and Upregulation of HIF-1

1
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
2
Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
3
Department of Urology, Taipei Medical University Shuang-Ho Hospital, New Taipei City 23561, Taiwan
4
TMU-Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan
5
International Medical Doctor Program, Vita-Salute San Raffaele University, 20132 Milan, Italy
6
Program of Biomedical Sciences, College of Arts and Sciences, California Baptist University, Riverside, CA 92504, USA
7
Department of Biotechnology, College of Medical and Health Care, Hungkuang University, Shalu District, Taichung 43302, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(9), 3400; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093400
Received: 21 March 2020 / Revised: 19 April 2020 / Accepted: 24 April 2020 / Published: 11 May 2020
(This article belongs to the Special Issue Mitochondria-Targeted Approaches in Health and Disease)
Combined androgen blockade using bicalutamide (Bic) is a therapeutic choice for treating prostate cancer (PCa). However, even at regular clinical dosages, Bic frequently shows adverse effects associated with cardiovascular and renal damage. Previously, we found that Bic selectively damaged mesangial cells compared to tubular cells and in an in vivo rat model, we also found renal damage caused by Bic. In the present study, a rat mesangial cell model was used to further the investigation. Results indicated that Bic enhanced lactate dehydrogenase release, reactive oxygen species (ROS) production, lysosome population and kidney injury molecule-1 and decreased N-cadherin. Bic elicited mitochondrial swelling and reduced the mitochondrial potential, resulting in severe suppression of the oxygen consumption rate (OCR), maximum respiration and ATP production. The hypoxia-inducible factor (HIF)-1 transcriptional activity and messenger RNA were significantly upregulated in dose-dependent manners. The HIF-1 protein reached a peak value at 24 h then rapidly decayed. BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 and cleaved caspase-3 were dose-dependently upregulated by Bic (60 M) and that eventually led to cell apoptosis. It is suggested that Bic induces renal damage via ROS and modulates HIF-1 pathway and clinically, some protective agents like antioxidants are recommended for co-treatment. View Full-Text
Keywords: bicalutamide (Bic); rat mesangial cell (RMC) line; mitochondrial dysfunction; HIF-1; oxygen consumption rate (OCR) bicalutamide (Bic); rat mesangial cell (RMC) line; mitochondrial dysfunction; HIF-1; oxygen consumption rate (OCR)
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MDPI and ACS Style

Chen, K.-C.; Chen, C.-R.; Chen, C.-Y.; Tzou, K.-Y.; Peng, C.-C.; Peng, R.Y. Bicalutamide Elicits Renal Damage by Causing Mitochondrial Dysfunction via ROS Damage and Upregulation of HIF-1. Int. J. Mol. Sci. 2020, 21, 3400. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093400

AMA Style

Chen K-C, Chen C-R, Chen C-Y, Tzou K-Y, Peng C-C, Peng RY. Bicalutamide Elicits Renal Damage by Causing Mitochondrial Dysfunction via ROS Damage and Upregulation of HIF-1. International Journal of Molecular Sciences. 2020; 21(9):3400. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093400

Chicago/Turabian Style

Chen, Kuan-Chou, Chang-Rong Chen, Chang-Yu Chen, Kai-Yi Tzou, Chiung-Chi Peng, and Robert Y. Peng. 2020. "Bicalutamide Elicits Renal Damage by Causing Mitochondrial Dysfunction via ROS Damage and Upregulation of HIF-1" International Journal of Molecular Sciences 21, no. 9: 3400. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093400

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