Bicalutamide exhibits potential to damage kidney via destroying complex i and affecting mitochondrial dynamics

Kuan Chou Chen, Chang Rong Chen, Chang Yu Chen, Chiung Chi Peng, Robert Y. Peng

研究成果: 雜誌貢獻文章同行評審

摘要

Bicalutamide (Bic) is an androgen deprivation therapy (ADT) for treating prostate can-cer, while ADT is potentially associated with acute kidney injury. Previously, we recognized Bic induced renal mitochondria dysfunction in vitro and in vivo via the ROS-HIF1α pathway. Whether OXPHOS complex, as well as mitochondrial dynamics, can be influenced by Bic via modulation of peroxisome proliferator-activated receptor coactivator 1α (PGC1α), NADPH oxidase 4 (Nox4), mitofusins 1/2 (MFN 1/2), optic atrophy 1 (OPA1), and sirtuins (SIRTs) has not been documented. Renal mesangial cell line was treated with Bic (30~60 µM) for the indicated time. SIRTs, complex I, mitochondrial dynamics-and oxidative stress-related proteins were analyzed. Bic dose-dependently reduced mitochondrial potential, but dose-and time-dependently suppressed translocase of the outer mitochondrial membrane member 20 (Tomm 20), complex I activity. Nox4 and glutathione lead to decreased NAD+ /NADH ratio, with upregulated superoxide dismutase 2. SIRT1 was initially stimulated and then suppressed, while SIRT3 was time-and dose-dependently downregulated. PGC1α, MFN2, and OPA1 were all upregulated, with MFN1 and pro-fission dynamin-related protein I downregulated. Bic exhibits potential to damage mitochondria via destroying complex I, complex I activity, and mitochondrial dynamics. Long-term treatment with Bic should be carefully followed up.
原文英語
文章編號135
期刊Journal of Clinical Medicine
11
發行號1
DOIs
出版狀態已發佈 - 1月 1 2022

ASJC Scopus subject areas

  • 醫藥 (全部)

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