Oral administration of the NADPH-oxidase inhibitor apocynin partially restores diminished cartilage proteoglycan synthesis and reduces inflammation in mice
Oral administration of the NADPH-oxidase inhibitor apocynin partially restores diminished cartilage proteoglycan synthesis and reduces inflammation in mice
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DOI：
10.1016/j.ejphar.2005.11.061
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发表时间：
2006-02-15
影响因子：
5
通讯作者：
Smit, HF
中科院分区：
文献类型：
--
作者：
Hougee, S;Hartog, A;Smit, HF
夹竹桃麻素是 NADPH 氧化酶的抑制剂，已知可以部分逆转软骨细胞中炎症介导的软骨蛋白多糖的合成。最近，据报道夹竹桃麻素可防止单核细胞中环氧合酶 (COX)-2 的表达。本研究旨在探讨夹竹桃麻素的这些体外特征是否可以在体内得到证实。在酵母聚糖诱导的急性关节炎小鼠模型中，口服罗布麻宁（0、3.2、16和80μg/ml，在饮用水中）并监测对软骨蛋白聚糖合成的影响。在酵母聚糖诱导的汽车炎症小鼠模型中，口服罗布麻宁（14 mg/kg/天，强饲法），并测量脂多糖 (LPS) 刺激的血细胞对耳朵肿胀和离体产生的前列腺素 E-2 (PGE(2)) 的影响。在这项研究中，布洛芬用作阳性对照（50 mg/kg/天，通过强饲法），动物接受载体作为阴性对照。罗布麻宁剂量依赖性地逆转关节炎关节软骨中蛋白聚糖合成的抑制。在80μg/ml罗布麻宁剂量下发现蛋白多糖合成具有统计学上显着的增加。罗布麻宁不影响对照膝关节的蛋白聚糖合成。与媒介物治疗组相比，14 mg/kg/天的罗布麻宁在注射酵母聚糖后 1、2 和 4 小时（小时）显着减少了酵母聚糖引起的耳部肿胀。体内夹竹桃麻素处理后，LPS刺激的血细胞离体产生的PGE(2)显着减少。布洛芬与罗布麻宁在同一时间点减少耳部肿胀，并抑制离体产生的 PGE。总之，本研究证实了罗布麻素在体内的两个重要特征：（1）口服罗布麻素可以部分逆转炎症诱导的软骨蛋白聚糖合成抑制；（2）口服罗布麻素具有与非甾体抗炎药（NSAID）布洛芬类似的COX抑制作用。因此，罗布麻素可能在治疗骨关节炎或类风湿性关节炎等慢性炎症性关节疾病方面具有潜在用途。 (c) 2005 Elsevier B.V.。保留所有权利。
Apocynin, an inhibitor of NADPH-oxidase, is known to partially reverse the inflammation-mediated cartilage proteoglycan synthesis in chondrocytes. More recently, it was reported that apocynin prevents cyclooxygenase (COX)-2 expression in monocytes. The present study aimed to investigate whether these in vitro features of apocynin could be confirmed in vivo. In a mouse model of zymosan-induced acute arthritis apocynin was administered orally (0, 3.2, 16 and 80 mu g/ml in the drinking water) and the effects on cartilage proteoglycan synthesis were monitored. In a mouse model of zymosan-induced inflammation of the cars apocynin was administered orally (14 mg/kg/day by gavage) and the effects on ear swelling and ex vivo produced prostaglandin E-2 (PGE(2)) by lipopolysaccharide (LPS)-stimulated blood cells were measured. In this study, ibuprofen was used as a positive control (50 mg/kg/day by gavage) and animals received vehicle as a negative control. Apocynin dose-dependently reversed the inhibition of proteoglycan synthesis in articular cartilage of the arthritic joint. A statistically significant increase in proteoglycan synthesis was found at a dose of 80 mu g/ml apocynin. Apocynin did not affect the proteoglycan synthesis of the control knee joints. Apocynin significantly decreased the zymosan-induced ear swelling at 1, 2 and 4 h (hours) after zymosan injection versus the vehicle treated group at 14 mg/kg/day. The ex vivo production of PGE(2) by LPS-stimulated blood cells was significantly decreased after in vivo apocynin treatment. Ibuprofen decreased ear swelling at the same time-points as apocynin and inhibited the ex vivo produced PGE,. In conclusion, the present study confirmed two important features of apocynin in vivo: (1) oral administration of apocynin can partially reverse the inflammation-induced inhibition of cartilage proteoglycan synthesis, and (2) oral administration of apocynin has COX inhibitory effects similar to the non-steroidal anti-inflammatory drug (NSAID) ibuprofen. Therefore, apocynin might be of potential use during the treatment of chronic inflammatory joint diseases like osteoarthritis or rheumatoid arthritis. (c) 2005 Elsevier B.V.. All rights reserved.