Sagir Ozlem, Sunay Fatma Bahar, Yildirim Hatice, Aksoz Elif, Ozaslan Sabri, Koroglu Ahmet, Aydemir Tugsen, Ulusal Ali Engin, Kockar Feray
Department of Anaestesiology & Reanimation, Medical Faculty, Balikesir University, Balikesir, Turkey.
Indian J Med Res. 2013 Dec;138(6):912-8.
BACKGROUND & OBJECTIVES: Intra-articular (ia) injections of local anaesthetics and non-steroidal anti-inflammatory drugs (NSAID's) are simple and efficient to ensure post-operative analgesia but some of these have toxic effects on the synovium and cartilage. Dexketoprofen is recently introduced S-enantiomer of ketoprofen with a better analgesic and side effect profile. This study was done to evaluate the possible toxic effects of dexketoprofen trometamol on knee joint cartilage and symovium in vitro and in vivo.
Forty one Sprague-Dawley rats were anaesthetized by ketamine. Dexketoprofen trometamol (0.25 ml) was injected into the right knee joint of the 35 rats and 0.25 ml serum physiologic into the left knee joint of the same animals. Six rats were sham operated. Thirty five animals were randomly divided into five equal groups. Seven animals were sacrified at 24th, 48th hours and 7th, 14th, and 21 st days of the injections. Haematoxylin eosin stained sections from the knee joints were evaluated for the signs of inflammation according to five point scale. Primary chondrocytes were isolated from the articular cartilages of rats for in vitro studies. Cells were exposed to 0.25 ml dexketoprofen trometamol or 0.25 ml dexketoprofen medium mixture at 1:1 ratio for 15, 30, 45 and 60 min. Cell viability was determined by 3-(4, 5- dimethylthiazole-2-yl)-2.5-diphenyl tetrazolium bromide (MTT) assay, 24, 48 and 72 h after drug treatment.
No significant histopathologic differences were found between dexketoprofen trometamol and physiologic serum (control) applied joints at all time intervals in in vivo study. Cell proliferation in dexketoprofen trometamol treated chondrocytes was inhibited for all time intervals compared to control. In dexketoprofen-medium mixture groups significant differences were only seen 24 h after the 30 and 45 min application of medium: drug mixture.
INTERPRETATION & CONCLUSIONS: Intra-articular application of dexketoprofen trometamol into the rat knee joints did not cause significant histopathological changes, but its in vitro application in primary chondrocyte culture caused significant cytotoxicity. The effects of dexketoprofen at different concentrations need to be further investigated in culture of rat and human chondrocytes.
关节内注射局部麻醉药和非甾体抗炎药是确保术后镇痛的简单有效方法，但其中一些药物对滑膜和软骨有毒性作用。右酮洛芬是最近引入的酮洛芬S-对映体，具有更好的镇痛和副作用特征。本研究旨在评估右酮洛芬氨丁三醇在体外和体内对膝关节软骨和滑膜的可能毒性作用。
41只Sprague-Dawley大鼠用氯胺酮麻醉。将右酮洛芬氨丁三醇（0.25 ml）注入35只大鼠的右膝关节，将0.25 ml生理血清注入同一动物的左膝关节。6只大鼠进行假手术。35只动物随机分为五组，每组7只。在注射后的第24小时、48小时以及第7天、14天和21天处死7只动物。对膝关节苏木精-伊红染色切片按照五点量表评估炎症迹象。从大鼠关节软骨分离原代软骨细胞用于体外研究。细胞分别暴露于0.25 ml右酮洛芬氨丁三醇或0.25 ml按1:1比例混合的右酮洛芬培养基中15、30、45和60分钟。在药物处理后24、48和72小时，通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法测定细胞活力。
在体内研究中，在所有时间间隔，右酮洛芬氨丁三醇处理组和生理血清（对照组）处理的关节之间未发现明显的组织病理学差异。与对照组相比，右酮洛芬氨丁三醇处理的软骨细胞在所有时间间隔的细胞增殖均受到抑制。在右酮洛芬-培养基混合组中，仅在培养基与药物混合物作用30和45分钟后24小时观察到显著差异。
将右酮洛芬氨丁三醇关节内注射到大鼠膝关节中未引起明显的组织病理学变化，但其在原代软骨细胞培养中的体外应用导致了显著的细胞毒性。右酮洛芬在不同浓度下的作用需要在大鼠和人类软骨细胞培养中进一步研究。
