Cheng Mi Hyun, Kim Sung-Jin
Department of Pharmacology and Toxicology, School of Dentistry, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
Biomol Ther (Seoul). 2020 Jan 1;28(1):104-109. doi: 10.4062/biomolther.2019.047.
Probenecid is a representative drug used in the treatment of gout. A recent study showed that probenecid effectively inhibits oxidative stress in neural cells. In the present study, we investigated whether probenecid can affect osteoclast formation through the inhibition of reactive oxygen species (ROS) formation in RAW264.7 cells. Lipopolysaccharide (LPS)-induced ROS levels were dose-dependently reduced by probenecid. Fluorescence microscopy analysis clearly showed that probenecid inhibits the generation of ROS. Western blot analysis indicated that probenecid affects two downstream signaling molecules of ROS, cyclooxygenase 2 (COX-2) and c-Jun N-terminal kinase (JNK). These results indicate that probenecid inhibits ROS generation and exerts antiosteoclastogenic activity by inhibiting the COX-2 and JNK pathways. These results suggest that probenecid could potentially be used as a therapeutic agent to prevent bone resorption.
丙磺舒是用于治疗痛风的代表性药物。最近一项研究表明，丙磺舒可有效抑制神经细胞中的氧化应激。在本研究中，我们调查了丙磺舒是否能通过抑制RAW264.7细胞中活性氧（ROS）的形成来影响破骨细胞的形成。丙磺舒可剂量依赖性地降低脂多糖（LPS）诱导的ROS水平。荧光显微镜分析清楚地表明丙磺舒可抑制ROS的产生。蛋白质印迹分析表明，丙磺舒影响ROS的两个下游信号分子，即环氧合酶2（COX-2）和c-Jun氨基末端激酶（JNK）。这些结果表明，丙磺舒可抑制ROS的产生，并通过抑制COX-2和JNK途径发挥抗破骨细胞生成活性。这些结果表明，丙磺舒有可能用作预防骨吸收的治疗剂。
