Study of anti-inflammatory and analgesic properties of 3-benzoyl-propionic acid
DOI:
https://doi.org/10.4322/prmj.2017.007Palavras-chave:
inflammation, analgesia, nonsteroidal anti-inflammatories (NSAIDs), 3-benzoyl-propionic acidResumo
Inflammation is an attempt by the body to remove noxious stimuli and initiate thus a cascade of responses in order to promote healing. There are a variety of inflammatory mechanisms involved in infections, chronic diseases and other tissue damage. Understanding these mechanisms and the search for new anti-inflammatory drugs with greater specificity and fewer side effects, underlying the development and improvement of new protocols and standardization of experimental inflammatory models to understand better these issues. The aim of this study was to evaluate the anti-inflammatory and analgesic activity of 3-benzoyl-propionic acid (3BPA) and its potential toxicological effect. To test the 3BPA as new anti-inflammatory and analgesic drug, the use carrageenan air pouch model 1% by in vitro model of cell culture to test genocytotoxicity. In the in vitro model the 3BPA presented low level of genotoxic and low cytotoxicity risk, shown by comet assay and no damage to the plasma membrane by hemolytic test erythrocytes. In the study of anti-inflammatory activityin vivo by the air pouch method were conducted nitrite dose trials, PGE2 levels and cell migration. To verify analgesic effects of 3BPA drugin vivo tests of abdominal contortions induced by acetic acid and formalin were performed. Regard to the anti-inflammatory activity, 3BPA showed intense activity shown in marked reduction of cell migration and levels of NO, with large populations of neutrophils and reduction of PGE 2 values at a dose of 0.5mg/kg. In studies of antinociceptive activity, 3BPA reduced the number of writhes and the time lick the neurogenic and inflammatory phases of the formalin test. The results of this study also advanced substantially with respect to anti-inflammatory and analgesic properties of 3BPA by providing evidence of their likely mechanism of action, through the evaluation of antinociceptive activity, as well as the anti-inflammatory activity in vitro and in vivo, where the 3BPA showed no genotoxic effect.
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Heidland A, Klassen A, Rutkowski P, Bahner U. The contribution of Rudolf Virchow to the concept of inflammation: what is still of importance? J Nephrol. 2006;19(Suppl 10):102-9. PMid:16874721.
Schmid-Schönbein GW. Analysis of inflammation. Annu Rev Biomed Eng. 2006;8(1):93-151. PMid:16834553. http://dx.doi.org/10.1146/annurev.bioeng.8.061505.095708.
Kenneth LR, Hajime K. The inflammatory response to cell death. Annual Review of Pathology-mechanisms of Disease. 2008;3(1):99-126. PMid:18039143. http://dx.doi.org/10.1146/annurev.pathmechdis.3.121806.151456.
Espinosa NF, Uebelhart B, Abrassart S. Use of NSAIDs in traumatology. Rev Med Suisse. 2014;25(436):1390-4. PMid:25055472.
Levoin N, Blondeaua C, Guillaumea C, Grandcolas L, Chretienb F, Jouzeaua JY, et al. Elucidation of the mechanism of inhibition of cyclooxygenases by acyl-coenzyme A and acylglucuronic conjugates of ketoprofen. Biochem Pharmacol. 2004;68(10):1957-69. PMid:15476667. http://dx.doi.org/10.1016/j.bcp.2004.07.015.
Costa D, Moutinho L, Lima JLFC, Fernandes E. Antioxidant activity and inhibition of human neutrophil oxidative burst mediated by arylpropionic acid non-steroidal anti- inflammatory drugs. Biol Pharm Bull. 2006;29(8):1659-70. PMid:16880623. http://dx.doi.org/10.1248/bpb.29.1659.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):1-2, 55-63. PMid:6606682. http://dx.doi.org/10.1016/0022-1759(83)90303-4.
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JK, Tannenbaum SR. Analysis of nitrate, nitrite and 15N in biological fluids. Anal Biochem. 1982;126(1):131-8. PMid:7181105. http://dx.doi.org/10.1016/0003-2697(82)90118-X.
Burlinson B, Tice RR, Speit G, Agurell E, Brendler-Schwaab SY, Collins AR, et al. Fourth International Workgroup on Genotoxicity testing: results of the in vivo Comet assay workgroup. Mutat Res. 2007;627(1):31-5. PMid:17118697. http://dx.doi.org/10.1016/j.mrgentox.2006.08.011.
Dobrovolskaia MA, Clogston JD, Neun BW, Hall JB, Patri AK, Mcneil SE. Method for analysis of nanoparticle hemolytic properties in vitro. Nano Lett. 2008;8(8):2180-7. PMid:18605701. http://dx.doi.org/10.1021/nl0805615.
Bastos GN, Silveira AJ, Salgado CG, Picanço-Diniz DL, Nascimento JLJ. Physalis angulata extract exerts anti-inflammatory effects in rats by inhibiting different pathways. J Ethnopharmacol. 2008;118(2):246-51. PMid:18513903. http://dx.doi.org/10.1016/j.jep.2008.04.005.
Koster R, Anderson M, Debeer EJM. Acetic acid for analgesic screening. Fed Proc. 1959;18:412.
Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain. 1977;4(2 Supp C):161-74. PMid:564014. http://dx.doi.org/10.1016/0304-3959(77)90130-0.
Wannmacher W, Passos LFS. Anti-inflamatórios não esteroides. In: Fuchs FD, Wannmacher L, editors. Farmacologia clínica: fundamentos da terapêutica racional. Rio de Janeiro: Guanabara Koogan; 2010. p. 408-421.
Hilário MOE, Terreri MT, Len CA. Non-steroidal anti-inflammatory drugs: cyclooxygenase2inhibitors. J Pediatr. 2006;82(5 Suppl):206-12. PMid:17136297. http://dx.doi.org/10.2223/JPED.1560.
Igarza L, Soraci A. Ácidos aril-2-propiónicos o profenos. Revista Médicas UIS. 2007;20:31-46.
Levoin N, Blondeaua C, Guillaumea C, Grandcolas L, Chretienb F, Jouzeaua JY, et al. Elucidation of the mechanism of inhibition of cyclooxygenases by acyl-coenzyme A and acylglucuronic conjugates of ketoprofen. Biochem Pharmacol. 2004;68(10):1957-69. PMid:15476667. http://dx.doi.org/10.1016/j.bcp.2004.07.015.
Takeda Chemical Industries. Un metodo para la preparacion de acido 3-(benzoil trisustituido)-propionico. Madrid, Espanha: Takeda Chemical Industries; 1975. Patente de invenção.
Kameo K, Ogawa K, Takeshita K, Nakaike S, Tomisawa K, Sota K. Studies on antirheumatic agents: 3-benzoylpropionic acid derivatives. Chem Pharm Bull. 1988;36(6):2050-60. PMid:3240440. http://dx.doi.org/10.1248/cpb.36.2050.
Kawashima Y, Kameo K, Kato M, Hasegawa M, Tomisawa K, Hatayama K, et al. Structure-activity studies of 3-benzoylpropionic acid derivatives suppressing adjuvant arthritis. Chem Pharm Bull. 1992;40(3):774-7. PMid:1611693. http://dx.doi.org/10.1248/cpb.40.774.
Brasil. Ministério da Saúde. Agência Nacional de Vigilância Sanitária – ANVISA. Resolução RDC nº 138, de 29 de maio de 2003. Dispõe sobre
o enquadramento na categoria de venda de medicamentos. Diário Oficial da República Federativa do Brasil, Brasília, DF, 02 jun. 2003.
Bakkali F, Averbeck S, Averbeck D, Idaomar M. Biological effects of essential oils-a review. Food Chem Toxicol. 2008;46(2):446-75. PMid:17996351. http://dx.doi.org/10.1016/j.fct.2007.09.106.
Cirino G, Wheeler-Jones CP, Wallace JL, Del Soldato P, Baydoun AR. Inhibition of inducible nitric oxide synthase expression by novel nonsteroidal anti-inflammatory derivatives with gastrointestinal-sparing properties. Br J Pharmacol. 1996;117(7):1421-6. PMid:8730734. http://dx.doi.org/10.1111/j.1476-5381.1996.tb15301.x.
Adams DO, Hamilton TA. The cell biology of macrophage activation. Annu Rev Immunol. 1984;2(1):283-318. PMid:6100475. http://dx.doi.org/10.1146/annurev.iy.02.040184.001435.
Vandghanooni S, Eskandani M. Comet assay: a method to evaluate genotoxicity of nano-drug delivery system. Bioimpacts. 2011;1(2):87-97. PMid:23678412.
Azqueta A, Collins AR. The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Arch Toxicol. 2013;87(6):949-
PMid:23685795. http://dx.doi.org/10.1007/s00204-013-1070-0.
Aparicio RM, José GCM, Pilar VM, Mitjans M. In vitro studies of the hemolytic activity of microemulsions in human erythrocytes. J Pharm Biomed Anal. 2005;39(5):1063-7. PMid:16054795. http://dx.doi.org/10.1016/j.jpba.2005.06.013.
Oliveira VMA, Carneiro ALB, Cauper GSB, Pohlit AM. In vitro screening of Amazonian plants for hemolytic activity and inhibition of platelet aggregation in human blood. Acta Amazon. 2009;39(4):973-80. http://dx.doi.org/10.1590/S0044-59672009000400026.
Andrade RB, Negrão CAB, Costa CEF, Bastos GNT. MCM-41 produzido por caulim da amazônia aumentou a biodisponibilidade de Ibuprofeno. In: Anais do 7º Congresso Latino Americano de Órgãos Artificiais e Biomateriais (COLAOB); 2012, Natal, Rio Grande do Norte. São Paulo: Metallum Eventos Técnicos e Científicos; 2012.
Selye H. Induction of topical resistance to acute tissue injury; an experimental study with the granuloma pouch technique. Surg Clin North Am. 1953;33(5):1417-46. PMid:13102197. http://dx.doi.org/10.1016/S0039-6109(16)34043-9.
Edwards JCW, Sedgwick AD, Willoughby DA. The formation of a structure with the features of synovial lining by the subcutaneous injection of air: an in vivo tissue culture system. J Pathol. 1981;134(2):147-56. PMid:7019400. http://dx.doi.org/10.1002/path.1711340205.
Ignarro LJ. Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol. 1990;30(1):535-60. PMid:2188578. http://dx.doi.org/10.1146/annurev.pa.30.040190.002535.
Griffith OW, Stuehr DJ. Nitric oxide synthases: and catalytic mechanism. Annu Rev Physiol. 1995;57(1):707-34. PMid:7539994. http://dx.doi.org/10.1146/annurev.ph.57.030195.003423.
Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001;357(3):593-615. PMid:11463332. http://dx.doi.org/10.1042/bj3570593.
Masukawa T, Nakanishi K, Natsuki R. Role of nitric oxide in the convulsions following the coadministration of enoxacin with fenbufen in mice. Jpn J Pharmacol. 1998;76(4):425-9. PMid:9623721. http://dx.doi.org/10.1254/jjp.76.425.
Sautebin L. Prostaglandins and nitric oxide as molecular targets for anti-inflammatory therapy. Fitoterapia. 2000;71(Suppl 1):48-57. PMid:10930713. http://dx.doi.org/10.1016/S0367-326X(00)00181-7.
Costa D, Moutinho L, Lima JLFC, Fernandes E. Antioxidant activity and inhibition of human neutrophil oxidative burst mediated by arylpropionic acid non-steroidal anti- inflammatory drugs. Biol Pharm Bull. 2006;29(8):1659-70. PMid:16880623. http://dx.doi.org/10.1248/bpb.29.1659.
Crews FT, Bechara R, Brown LA, Guidot DM, Mandrekar P, Oak S, et al. Cytokines and alcohol. Alcohol Clin Exp Res. 2006;30(4):720-30. PMid:16573591. http://dx.doi.org/10.1111/j.1530-0277.2006.00084.x.
Ulbrich H, Eriksson E, Lindbom L. Leukocyte and endothelial cell adhesion molecules as targets for therapeutic interventions in inflammatory disease. Trends Pharmacol Sci. 2003;24(12):640-7. PMid:14654305. http://dx.doi.org/10.1016/j.tips.2003.10.004.
Domíguez-Luis M, Herrera-García A, Arce-Franco M, Armas-González E, Rodríguez-Pardo M, Lorenzo-Díaz F, et al. Superoxide anion mediates the L-selectin down- regulation induced by non-steroidal anti-inflammatory drugs in human neutrophils. Biochem Pharmacol. 2013;85(2):245-56. PMid:23142710. http://dx.doi.org/10.1016/j.bcp.2012.10.024.
Benez FHN, Oliveira CC, Acedo SC, Gotardo EMF, Câmara LE, Calafatti S, et al. Comparative study of anti-inflammatory, ulcerogenic and cytotoxic activities of racemate and S-ibuprofen. Rev Cienc Farm Basica Apl. 2013;34(3):327-32.
Shalaby MR, Waage A, Espernik T. Cytokine regulation of Interleukin-6 production by human endothelial cells. Cell Immunol. 1989;121(2):372-
PMid:2500254. http://dx.doi.org/10.1016/0008-8749(89)90036-1.
Bresnihan B. Rheumatoid arthritis: principles of early treatment. J Rheumatol. 2002;29(66):9-1. PMid:12435163.
Jiang J, Wu F, Lu J, Xu Q. Anti-inflammatory activity of the aqueous extract from Rhizoma Smilacis Glabrae. Pharmacol Res. 1997;36(4):309-
PMid:9425621. http://dx.doi.org/10.1006/phrs.1997.0234.
Chabaud M, Fossiez F, Taupin JL, Miossec P. Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol. 1998;161(1):409-14. PMid:9647250.
Shin S, Jeon JH, Park D, Jang JY, Joo SS, Hwang BY, et al. Anti-inflammatory effects of an ethanol extract of angelica gigas in a carragenan-air pouch inflammation model. Exp Anim. 2009;58(4):431-6. PMid:19654443. http://dx.doi.org/10.1538/expanim.58.431.
Alarcón de La Lastra C, Nieto A, Martín MJ, Cabré F, Herrerías JM, Motilva V. Gastric toxicity of racemic ketoprofen and its enantiomers in rat: oxygen radical generation and COX-expression. Inflamm Res. 2002;51(2):51-7. PMid:11930903. http://dx.doi.org/10.1007/BF02683999.
Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature. 2001;413(6852):203-10. PMid:11557989. http://dx.doi.org/10.1038/35093019.
Espinosa NF, Uebelhart B, Abrassart S. Use of NSAIDs in traumatology. Rev Med Suisse. 2014;25(436):1390-4. PMid:25055472.
Ikeda Y, Ueno A, Naraba H, Oh-Ishi S. Involvement of vanilloid receptor VR1 and prostanoids in the acid-induced writhing responses of mice. Life Sci. 2001;69(24):2911-9. PMid:11720094. http://dx.doi.org/10.1016/S0024-3205(01)01374-1.
Capone, F.; Aloisi, A.M. Refinement of pain evaluation techniques. The formalin test. Ann Ist Super Sanita. 2004; 40(2),2:223:9.
Gonçalves JCR, Oliveira FS, Benedito RB, Sousa DP, Almeida RN, Araújo DAMAD. Antinociceptive activity of (-)-Carvone: Evidence of association with decreased peripheral nerve excitability. Biol Pharm Bull. 2008;31(5):1017-20. PMid:18451538. http://dx.doi.org/10.1248/bpb.31.1017.
Vanegas H, Schaible H-G. Descending control of persistent pain: inhibitory or facilitatory? Brain Res Brain Res Rev. 2004;46(3):295-309. PMid:15571771. http://dx.doi.org/10.1016/j.brainresrev.2004.07.004.
Oliveira FS, Sousa DP, Almeida RN. Antinociceptive. Effect of hydroxydihydrocarvone. Biol Pharm Bull. 2008;31(4):588-91. PMid:18379046. http://dx.doi.org/10.1248/bpb.31.588.
