Abstract
—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.
Similar content being viewed by others
References
Bakhle, Y. S. and Botting, R. M. (1996). Cyclooxygenase-2 and its regulation in inflammation mediators, Inflammation 5, 305–23.
Cayetti, L. M., de los Santos, A. R., Marti, M. L., Di Girolamo, G. and Niselman, V. (1995). Lysine clonixinate versus aspirin in the treatment of gonarthrosis, Curr. Then Res. 56, 894–905.
Chan, C. L., Boyce, S., Brideau, C., Ford Hutchinsion, A.W., Gordon, R., Guay, D. et al. (1995). Pharmacology of a selective cyclooxygenase 2 inhibitor 1-74337; a novel nonsteroidal anti- inflammatory agent with an ulcerogenic sparing effect in rat and non-human primate stomach, J. Pharmacol. Exp. Then 274, 153–7.
Feng, I., Sun, W., Xia, Y, Tang, W. W., Chanmigan, P. et al. (1993). Cloning two isoforms of rat cyclooxygenase: differential regulations of their expression, Arch. Biochem. Biophys. 307, 361–8.
Franchi, A. M., Di Girolamo, G., de los Santos, A. R., Marti, M. C. and Gimeno, M. A. F. (1998). Effects of lysine clonixinate on cyclooxygenase I and II in rat lung and stomach preparations, Prost. Leuk. & Essential Fatty Acids 58, 421–24.
Futaki, N., Yoshikawa, K., Arai, I., Gguchi, S., Lizuka, H. et al. (1993). NS 398 a novel nonsteroidal anti-inflammatory drug with potent analgesic and antipyretic effects, which causes minimal stomach lesions, Gen. Pharmacol. 24, 105–10.
Gimeno, M. A. F., Borda, E. S., Sterin-Borda, L., Vidal, J. and Gimeno, A. L. (1976). Pharmacologie influences on human ovarian contractions, Obstet. Gynecol NY 47, 218–22.
Grossman, C. J., Wiseman, J., Lucas, F. S. et al. (1995). Inhibition of constitutive and inducible cyclooxygenase activity in human platelet and mononuclear cells by NSAIDS and COX-2 inhibitors, Inflamm. Res. 44, 253–7.
Masferrer, H., Zuwifel, B. S., Manning, P. T., Hauser, S. D., Leakg, K. M., Smith, W. G. et al. (1994). Selective inhibition of inducible cyclooxygenase 2 in vivo is anti-inflammatory and non- ulcerogenic, Proc. Natl. Acad. Sci. USA 91, 3228–32.
Masferser, J. L., Isakson, P. C. and Seibert, I. (1966). Cyclooxygenase 2 inhibitors. A new class of anti-inflammatory agents that spare gastrointestinal tract, Gastroenterology Clinics of North America 25, 363–72.
Meade, E. A., Smith, W. L. and De Witt, D. L. (1993). Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isoenzymes by aspirin and other non-steroid anti- inflammatory drugs, J. Biol. Chem. 268, 6610–4.
Pico, J. C., Monti, C. E. A., de Buacar, N. R. W., Martinez, M., Aldomá, G. E., Mitta, A. E. (1981). Pharmacokinetic study of 2-(2′-methyl-3′-chloro-anilino) lysine nicotiname (L-104), Arzneim- Forsch Drug Res. 31, 1127–30.
Simmonsons, D. L., Xie, W., Evett, G., Merril, J., Robertson, D. L., Bradshaw, W. S. (1993). Drug inhibition and cellular regulation of prostaglandin GH synthase isoenzyme-2, J. Lipid Mediat. 6, 113–7.
Strarman, N. C., Carter, D. B. and Sethey, V. H. (1997). Ibuprofen: effect on inducible nitric oxide synthase, Molecular Brain Research 50, 107–12.
Vane, J. R. and Botting R. M. (1995). New insights into the mode of action of anti-inflammatory drugs, Inflamm. Res. 44, 1–10.
Wallace, J. L. (1994). The 1994 Merck Frost Award. Mechanisms of nonsteroidal anti-inflammatory (NSAID) induced gastrointestinal damage, potential for development of gastrointestinal tract safe NSAIDs, Can. J. Physiol. Pharmacol, 1493–8.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Franchi, A.M., Girolamo, G.D., De LosSantos, A.R. et al. Ex vivo effects of lysine clonixinate on cyclooxygenases in rat lung and stomach preparations. Inflammopharmacol 7, 401–411 (1999). https://doi.org/10.1007/s10787-999-0033-9
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10787-999-0033-9