PMID- 31927051
OWN - NLM
STAT- MEDLINE
DCOM- 20200615
LR  - 20200615
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 253
DP  - 2020 Jul 15
TI  - Nifedipine inhibits oxidative stress and ameliorates osteoarthritis by activating 
      the nuclear factor erythroid-2-related factor 2 pathway.
PG  - 117292
LID - S0024-3205(20)30039-4 [pii]
LID - 10.1016/j.lfs.2020.117292 [doi]
AB  - Nifedipine is a voltage-gated calcium channel inhibitor widely used in the 
      treatment of hypertension. Nifedipine has been reported to have antioxidant and 
      anti-apoptotic effects and promotes cell proliferation. However, the effects of 
      nifedipine on oxidative stress and apoptosis in osteoarthritic (OA) chondrocytes 
      are still unclear. In this study, we sought to investigate whether nifedipine 
      alleviates oxidative stress and apoptosis in OA through nuclear factor 
      erythroid-2-related factor 2 (Nrf2) activation. The cytotoxicity of nifedipine 
      against human chondrocytes was detected using a 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) kit, whereas 
      mRNA and protein expression levels were measured using reverse 
      transcription-polymerase chain reaction (RT-PCR) and Western blotting, 
      respectively. The oxidative stress level was analyzed by measuring reactive 
      oxygen species (ROS), glutathione peroxidase (GSH-px), catalase (CAT) and 
      superoxide dismutase (SOD) activities. The role of Nrf2 in the effect of 
      nifedipine on OA was analyzed using an Nrf2 inhibitor brusatol (BR). The result 
      showed that nifedipine inhibited the expression of matrix metalloprotein(MMP)-13, 
      interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, cyclooxygenase (COX)-2, 
      inducible nitric oxide (NO) synthase (iNOS), and prostaglandin E2 (PGE2), as well 
      as reduced ROS production in human OA chondrocytes, which was partially reversed 
      by BR. Nifedipine prevented cartilage degeneration and contributed to the 
      expression of Nrf-2 in chondrocytes. These results indicate that nifedipine 
      inhibited inflammation and oxidative stress in chondrocytes via activation of 
      Nrf-2/HO-1 signaling.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Yao, Jun
AU  - Yao J
AD  - Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi 
      Medical University, 530021 Nanning, China; Guangxi Collaborative Innovation 
      Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical 
      University, 530021, Nanning, China; The First Affiliated Hospital of Guangxi 
      Medical University, 530021 Nanning, China.
FAU - Long, Huiping
AU  - Long H
AD  - The First Affiliated Hospital of Guangxi Medical University, 530021 Nanning, 
      China.
FAU - Zhao, Jianping
AU  - Zhao J
AD  - Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi 
      Medical University, 530021 Nanning, China; The First Affiliated Hospital of 
      Guangxi Medical University, 530021 Nanning, China.
FAU - Zhong, Gang
AU  - Zhong G
AD  - Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi 
      Medical University, 530021 Nanning, China; Guangxi Collaborative Innovation 
      Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical 
      University, 530021, Nanning, China; The First Affiliated Hospital of Guangxi 
      Medical University, 530021 Nanning, China. Electronic address: 
      13257788667@163.com.
FAU - Li, Jia
AU  - Li J
AD  - The First Affiliated Hospital of Guangxi Medical University, 530021 Nanning, 
      China; Department of Pathology, First Affiliated Hospital of Guangxi Medical 
      University, 530021 Nanning, China. Electronic address: jialee2005@126.com.
LA  - eng
PT  - Journal Article
DEP - 20200109
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Interleukins)
RN  - 0 (Metalloproteins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Quassins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 14907-98-3 (brusatol)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - I9ZF7L6G2L (Nifedipine)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Aged
MH  - Apoptosis
MH  - Calcium Channel Blockers/*metabolism/pharmacology
MH  - Catalase/metabolism
MH  - Chondrocytes/cytology/metabolism
MH  - Cyclooxygenase 2/metabolism
MH  - Dinoprostone/metabolism
MH  - Female
MH  - Gene Expression Regulation
MH  - Glutathione Peroxidase/metabolism
MH  - Humans
MH  - Interleukins/metabolism
MH  - Male
MH  - Metalloproteins/metabolism
MH  - Middle Aged
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Nifedipine/antagonists & inhibitors/*metabolism/pharmacology
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Osteoarthritis/*drug therapy
MH  - Oxidative Stress/*drug effects
MH  - Quassins/chemistry/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - Superoxide Dismutase/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Inflammation
OT  - Nifedipine
OT  - Nrf2/HO-1 pathway
OT  - Osteoarthritis
OT  - Oxidative stress
COIS- Conflicts of interest We declare that we have no conflict of interest.
EDAT- 2020/01/14 06:00
MHDA- 2020/06/17 06:00
CRDT- 2020/01/14 06:00
PHST- 2019/10/13 00:00 [received]
PHST- 2019/12/23 00:00 [revised]
PHST- 2020/01/07 00:00 [accepted]
PHST- 2020/01/14 06:00 [pubmed]
PHST- 2020/06/17 06:00 [medline]
PHST- 2020/01/14 06:00 [entrez]
AID - S0024-3205(20)30039-4 [pii]
AID - 10.1016/j.lfs.2020.117292 [doi]
PST - ppublish
SO  - Life Sci. 2020 Jul 15;253:117292. doi: 10.1016/j.lfs.2020.117292. Epub 2020 Jan 
      9.