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.

中文翻译：

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硝苯地平通过激活核因子红系-2相关因子2途径抑制氧化应激并改善骨关节炎。

硝苯地平是一种电压门控钙通道抑制剂，广泛用于治疗高血压。据报道，硝苯地平具有抗氧化和抗凋亡作用，并能促进细胞增殖。但是，硝苯地平对骨关节炎（OA）软骨细胞氧化应激和凋亡的影响尚不清楚。在这项研究中，我们试图调查硝苯地平是否通过核因子红系2相关因子2（Nrf2）的活化来减轻OA中的氧化应激和细胞凋亡。使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴甲烷（MTT）试剂盒检测了硝苯地平对人软骨细胞的细胞毒性，而使用逆转录聚合酶链反应检测了mRNA和蛋白质表达水平反应（RT-PCR）和蛋白质印迹。通过测量活性氧（ROS），谷胱甘肽过氧化物酶（GSH-px），过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性来分析氧化应激水平。使用Nrf2抑制剂Brusatol（BR）分析了Nrf2在硝苯地​​平对OA的作用中的作用。结果表明硝苯地平抑制基质金属蛋白（MMP）-13，白介素（IL）-1β，IL-6，肿瘤坏死因子（TNF）-α，环氧合酶（COX）-2，诱导型一氧化氮（NO）的表达合酶（iNOS）和前列腺素E2（PGE2），以及人OA软骨细胞中ROS的产生减少，BR对此产生了部分逆转。硝苯地平可防止软骨变性，并有助于软骨细胞中Nrf-2的表达。