in vitro EVALUATION OF NAPROXEN METABOLITE, 6-O-DESMETHYLNAPROXEN ON A MOUSE CONNECTIVE TISSUE FIBROBLAST CELLS

Esin Akbay, Y. D. Aracagök, Ali Hakan Göker, M. A. Onur, N. Cihangir
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Abstract

The aim of this in vitro study was assessment of the cytotoxic level of O-desmethylnaproxen. A mouse connective tissue fibroblast cell line, L929 was exposed to naproxen and O-desmethylnaproxen in different concentrations for 24and 48hours. Cell viability was tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphnyltetrazolium bromide (MTT), while apoptosis was determined by acridine orange/propidium iodide (AO/PI) double staining method. The control group was free from any agent (Dulbecco’s Modified Eagle’s Medium (DMEM) only) and accepted as 100% cell viability. The IC50 results indicated that the inhibition of 50% cell viability was resulted by the highest concentration of O-desmethylnaproxen (0.7 μg/mL) while none of naproxen concentration was caused 50% cell death. Consequently, to avoid the unacceptable side effects of naproxen metabolites that evacuated by urine; further studies should be conducted to determine the accumulation of naproxen metabolites.
萘普生代谢物6- o -去甲基萘普生对小鼠结缔组织成纤维细胞的体外评价
本体外研究的目的是评估o -去甲基萘普生的细胞毒性水平。将小鼠结缔组织成纤维细胞株L929分别暴露于不同浓度的萘普生和o -去甲基萘普生中24和48小时。采用3-[4,5-二甲基噻唑-2-酰基]-2,5-二苯基溴化四唑(MTT)检测细胞活力,采用吖啶橙/碘化丙啶(AO/PI)双染色法检测细胞凋亡。对照组不使用任何制剂(仅使用Dulbecco 's Modified Eagle 's Medium (DMEM)),并接受100%细胞存活率。IC50结果表明,最高浓度的o -去甲基萘普生(0.7 μg/mL)可抑制50%的细胞活力,但任何浓度的萘普生均未引起50%的细胞死亡。因此,为了避免萘普生代谢物通过尿液排出的不可接受的副作用;应该进行进一步的研究来确定萘普生代谢物的积累。
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