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Life Sci. 2020 Jan 9:117292. doi: 10.1016/j.lfs.2020.117292. [Epub ahead of print]

Nifedipine inhibits oxidative stress and ameliorates osteoarthritis by activating the nuclear factor erythroid-2-related factor 2 pathway.

Author information

1
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.
2
The First Affiliated Hospital of Guangxi Medical University, 530021 Nanning, China.
3
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.
4
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.
5
The First Affiliated Hospital of Guangxi Medical University, 530021 Nanning, China; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 530021 Nanning, China.

Abstract

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)-1β, IL-6, tumor necrosis factor (TNF)-α, 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.

KEYWORDS:

Inflammation; Nifedipine; Nrf2/HO-1 pathway; Osteoarthritis; Oxidative stress

PMID:
31927051
DOI:
10.1016/j.lfs.2020.117292
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