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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number135
JournalJournal of Clinical Medicine
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 1 2022

Keywords

  • Bicalutamide
  • Complex I NDUFB8
  • Glutathione (GSH)
  • Mitofusins 1/2 (MFN 1/2)
  • NADPH oxidase 4 (Nox4)
  • Optic atrophy 1 (OPA1)
  • PGC1α
  • Sirtuins (SIRTs)1/3
  • Superoxide dismutase 2 (SOD2)

ASJC Scopus subject areas

  • Medicine(all)

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