Evaluation of the effects of dexketoprofen trometamol on knee joınt: an in vivo & in vitro study
Ozlem Sagir1, Fatma Bahar Sunay2, Hatice Yildirim3, Elif Aksoz4, Sabri Ozaslan1, Ahmet Koroglu1, Tugsen Aydemir3, Ali Engin Ulusal5, Feray Kockar3
1 Department of Anaestesiology & Reanimation, Medical Faculty, Balikesir University, Balikesir, Turkey
2 Department of Histology & Embryology, Medical Faculty, Balikesir University, Balikesir, Turkey
3 Department of Biology, Faculty of Art & Science, Balikesir University, Balikesir, Turkey
4 Department of Pharmacology, Medical Faculty, Balikesir University, Balikesir, Turkey
5 Department of Orthopedics & Traumatology, Medical Faculty, Balikesir University, Balikesir, Turkey
Assistant Professor, Balikesir University, Faculty of Medicine, Department of Anaesthesiology & Reanimation, 10145, Balikesir
Source of Support: None, Conflict of Interest: None
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.
Methods: 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 24 th , 48 th hours and 7 th , 14 th , 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.
Results: 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.