Ex vivo effects of lysine clonixinate on cyclooxygenases in rat lung and stomach preparations

被引:5
作者
Franchi A.M. [1 ]
Di Girolamo G. [2 ]
De Lossantos A.R. [3 ]
Marti M.L. [3 ]
Gimeno M.A.F. [1 ]
机构
[1] Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Cientificas y Técnicas (CONICET)
[2] Segunda Cátedra de Farmacologia, Facultad de Medicina, Universidad de Buenos Aires
[3] Hospital de Clinicas José de San Martin, Facultad de Medicina, Universidad de Buenos Aires
关键词
Anti-inflammatory drug; Cyclooxygenase; Lysine clonixinate;
D O I
10.1007/s10787-999-0033-9
中图分类号
学科分类号
摘要
Lysine clonixinate (LC) is an anti-inflammatory, anti-pyretic and analgesic drug with minor digestive side effects, which might suggest a weak COX-1 inhibitor. The aim of this study focused on ex vivo effects of LC 40 mg/kg ip and indomethacin (INDO) 10 mg/kg ip in lung and stomach preparations of control rats and LPS-treated rats (5 mg/kg ip). The non-steroidal antiinflammatory drugs were administered concomitantly, following three hours and before one, two or three hours of LPS treatment. Tissues were weighed and incubated in 2 ml of Kress Ringer Bicarbonate buffer containing glucose (11 mM) under an atmosphere of 95% oxygen and 5% CO2. Approximately 200 mg of tissue were used for each determination; 0.25 μCi of 14C-arachidonic acid was added to each tube and the tissues were incubated for 60 min. Prostanoids were extracted from the incubation medium and separated by TLC. Results were expressed as a percentage of the total radioactivity of the plates (% of cpm on plate/100 mg ww). It was found that LC animals that were not given LPS did not modify the synthesis of PGE2; in lung and stomach tissues showing that did not inhibit COX-1 activity. However, LC inhibited clearly the synthesis of PGE2 in both preparations obtained from LPS-treated animals. The inhibition was shown when the rats were treated concomitantly, 3 h after or 1 or 2 h before the injection of LPS.
引用
收藏
页码:401 / 411
页数:10
相关论文
共 16 条
[1]  
Bakhle Y.S., Botting R.M., Cyclooxygenase-2 and its regulation in inflammation mediators, Inflammation, 5, pp. 305-23, (1999)
[2]  
Cayetti L.M., Santos A.R., Marti M.L., Girolamo G., Niselman V., Lysine clonixinate versus aspirin in the treatment of gonarthrosis, Curr. Then Res., 56, pp. 894-905, (1995)
[3]  
Chan C.L., Boyce S., Brideau C., Ford Hutchinsion A.W., Gordon R., Guay D., Pharmacology of a selective cyclooxygenase 2 inhibitor 1-74337
[4]  
a novel nonsteroidal anti- inflammatory agent with an ulcerogenic sparing effect in rat and non-human primate stomach, J. Pharmacol. Exp. Then, 274, pp. 153-7, (1995)
[5]  
Feng I., Sun W., Xia Y, Tang W.W., Chanmigan P., Cloning two isoforms of rat cyclooxygenase: differential regulations of their expression, Arch. Biochem. Biophys., 307, pp. 361-8, (1993)
[6]  
Franchi A.M., Girolamo G., Santos A.R., Marti M.C., Gimeno M.A.F., Effects of lysine clonixinate on cyclooxygenase I and II in rat lung and stomach preparations, Prost. Leuk. & Essential Fatty Acids, 58, pp. 421-24, (1998)
[7]  
Futaki N., Yoshikawa K., Arai I., Gguchi S., Lizuka H., NS 398 a novel nonsteroidal anti-inflammatory drug with potent analgesic and antipyretic effects, which causes minimal stomach lesions, Gen. Pharmacol., 24, pp. 105-10, (1993)
[8]  
Gimeno M.A.F., Borda E.S., Sterin-Borda L., Vidal J., Gimeno A.L., Pharmacologie influences on human ovarian contractions, Obstet. Gynecol NY, 47, pp. 218-22, (1976)
[9]  
Grossman C.J., Wiseman J., Lucas F.S., Inhibition of constitutive and inducible cyclooxygenase activity in human platelet and mononuclear cells by NSAIDS and COX-2 inhibitors, Inflamm. Res., 44, pp. 253-7, (1995)
[10]  
Masferrer H., Zuwifel B.S., Manning P.T., Hauser S.D., Leakg K.M., Smith W.G., Selective inhibition of inducible cyclooxygenase 2 in vivo is anti-inflammatory and non- ulcerogenic, Proc. Natl. Acad. Sci. USA, 91, pp. 3228-32, (1994)