Gabapentin improves colonic inflammatory damage and oxidative stress on acetic acid-induced colitis independent of cannabinoid pathway

Authors

DOI:

https://doi.org/10.33448/rsd-v10i7.16693

Keywords:

Anti-inflammatory; Colitis; Inflammation; Antioxidant; Gastrointestinal tract; Gabapentin.

Abstract

Objective: Gabapentin (GBP) possess a systemic anti-inflammatory action confirmed and endocannabinoids system have been effectives in reduces inflammatory disorders on intestinal tract. The aim of this study is evaluate the participation of the endogenous cannabinoids pathway in the anti-inflammatory and antioxidant effects of GBP in acetic acid (AA) induced colitis in mice. Methods: Colitis induction was performed using AA (6%) and mice treated intraperitoneally with GBP or dexamethasone (subcutaneously) at 17 h or 17:30 h after induction of colitis, respectively. After 18 h of colitis induction, the animals were euthanized and colonic sample was taken for evaluation of macroscopic and microscopic lesion, wet weight and biochemical analyzes. Results: The administration of GBP was effective in reduce the macro and microscopic lesions, significant decreasing the colonic wet weight of colitis mice. The drug reduced the concentration myeloperoxidase (MPO), malondialdehyde (MDA) and interleukin 1 (IL-1) and increased the level glutathione (GSH) in colitis mice compared to normal mice. The treatment with endocannabinoids (ECs) receptors antagonists did not alter the GBP effect. Conclusion: Gabapentin was able to reduce inflammatory parameters in acid acetic-induced colitis, but its effect seems to be independent of cannabinoid pathway.

Author Biographies

Diva de Aguiar Magalhães, Federal University of the Parnaíba Delta

 

 

 

 

 

 

 

 

Felipe Rodolfo Pereira da Silva, Federal University of the Parnaíba Delta

 

 

 

 

 

 

 

 

 

 

 

 

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References

Abdel-Salam, O. M. E. & Sleem, A. A. (2009). Study of the analgesic, anti-inflammatory, and gastric effects of gabapentin. Drug. Discov. Therapeutic, 3(1), 18–26.

Amirshahrokhi, K. Bohlooli, S. & Chinifroush, M. M. (2011). The effect of methylsulfonylmethane on the experimental colitis in the rat. Toxicol. Appl. Pharmacol, 253(3), 197–202.

Appleyard, C. B. & Wallace, J. L. (1995). Reactivation of hapten-induced colitis and its prevention

by anti- inflammatory drugs. Am. J. Physiol, 269(1), G119–25.

Arendt-Nielsen, L. Frøkjær, J. B. Staahl, C. Graven-Nielsen, T. Huggins, J. P. Smart, T. S. & Drewes, A. M. (2007). Effects of Gabapentin on Experimental Somatic Pain and Temporal Summation. Regional Anesthesia and Pain Medicine, 32(5), 382–388.

Brito, T. V. Barros, F. C. N. Silva, R. O. Dias Júnior, G. J. Júnior, J. S. Franco, C. Á. X. Soares, P. M. G. Chaves, L. S. Abreu, C. M. W. S. de Paula, R. C. M. Souza, M. H. L. P. Freitas, A. L. P, & Barbosa, A. L. R. (2016). Sulfated polysaccharide from the marine algae Hypnea musciformis inhibits TNBS-induced intestinal damage in rats. Carbohydrate Polymers, 151, 957–964.

Brito, T. V. Júnior, G. J. D. da Cruz Júnior, J. S. Silva, R. O. da Silva Monteiro, C. E. Franco, A. X. Vasconcelos, D. F. P. de Oliveira, J. S. Costa, D. V. S. Carneiro, T. B. Duarte, A. S. G. Souza, M. H. L. P Soares, P. M. G. & Barbosa, A. L. R. (2020) Gabapentin attenuates intestinal inflammation: Role of PPAR-gamma receptor. Eur J Pharmacol, 873 (2020), 172974.

Dias, J. M. de Brito, T. V. Magalhães, D. A. Santos, P. W. S. Batista, J. A. Nascimento Dias, E. G. Fernandes, H. B. Damasceno, S. R. B. Silva, R. O. Aragão, K. S. Souza, M. H. L. P. Medeiros, J. V. R. & Barbosa, A. L. R. (2014). Gabapentin, a synthetic analogue of gamma aminobutyric acid, reverses systemic acute inflammation and oxidative stress in mice. Inflammation, 37(5), 1826–1836.

Grisham, M. B. Yamada, T. Specian, R. D. & Grisham, M. B. (1992). A comparative analysis of two models of colitis in rats. Gastroenterology, 102(5), 1524-34.

Guazelli, C. F. S. Fattori, V. Colombo, B. B. & Georgetti, S, R. (2013). Quercetin-Loaded Microcapsules Ameliorate Experimental Colitis in Mice by Anti-inflammatory and Antioxidant Mechanisms. Journal of Nataral Products, 76(2), 200–208.

Halliwell, B. (1996). Antioxidants in human health and disease. Ann. Rev. Nutr, 16, 33–50.

Hoppa, M. B. Lana, B. Margas, W. Dolphin, A. C. & Ryan, T. A. (2012). α2δ expression sets presynaptic calcium channel abundance and release probability. Nature, 486(7401), 122–125.

Ihenetu, K. Molleman, A. Parsons, M. & Whelan, C. (2003). Pharmacological characterisation of cannabinoid receptors inhibiting interleukin 2 release from human peripheral blood mononuclear cells. Eur. J. Pharmacol, 464(2-3), 207–215.

Izzo, A. A. & Camilleri, M. (2009). Cannabinoids in intestinal inflammation and cancer. Pharmacol Res, 60(2), 117–25.

Katz, J. A. Itoh, J. & Fiocchi, C. (1999) Pathogenesis of inflammatory bowel disease. Curr. Opin. Gastroenterol, 15(4), 291–297.

Kayal, M. & Shah, S. (2019). Ulcerative Colitis: Current and Emerging Treatment Strategies. J Clin Med, 9(1), 94.

Khor, B. Gardet, A. & Xavier, R. J. 2011. Genetics and pathogenesis of inflammatory bowel disease. Nature, 474 (7351), 307–317.

Klein, T. W. Newton, C. Larsen, K. Lu, L. Perkins, I. & Nong, L. (2003). The cannabinoid system and immune modulation. J. Leukoc. Biol, 74(4), 486–96.

Lee, J. Y. Kang, H. S. Park, B. E. Moon, H. J. Sim, S. S. Kim, C. J. J. (2009). Inhibitory effects of Geijigajakyak-Tang on trinitrobenzene sulfonic acid-induced colitis. Ethnopharmacol, 126(2), 244−251.

Lynch, W. D. & Hsu, R. (2020). Ulcerative Colitis. StatPearls.

Marquéz, L, Suárez, J. Iglesias, M. Bermudez-Silva, F. J. De Fonseca, F. R. & Andreu, M. (2009). Ulcerative Colitis Induces Changes on the Expression of the Endocannabinoid System in the Human Colonic Tissue. Plos One, 4(9), e6893.

Martin, A. R. Villegas, I. La Casa, C. & La Lastra, C. A. (2004). Resveratrol, a polyphenol found in grapes, suppresses oxidative damage and stimulates apoptosis during early colonic inflammation in rats. Biochem Pharmacol, 67(7), 1399–410.

Massa, F. Marsicano, G. Hermann, H. Cannich, A. Monory, K. Cravatt, B. F. Ferri, G. L. Sibaev, A. Storr, M. & Lutz, B. (2004). The end ogenous cannabinoid system protects against colonic inflammation. J Clin Investig, 113(8), 1202–1209.

Mihara, M. & Uchiyama, M. (1978). Determination of malondialdehyde precursor in tissue by thiobarbituric acid test. Anal Biochem, 86(1), 271–278.

Morris, G. P. Beck, P. L. Herridge, M. S. Depew, W. T. Szewczuk, M. R. & Wallace, J. L. (1989). Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology, 96(3), 795–803.

O’Sullivan, S. E. (2016). An update on PPAR activation by cannabinoids. Br J Pharmacol, 173(12), 1899–910.

Podolsky, D. K. (1991). Inflammatory bowel disease (Review article). N Engl J Medicine, 325(14), 1008–1016.

Pereira, A. S. Shitsuka, D. M. Parreira, F. J. & Shitsuka R. (2018). METODOLOGIA DA PESQUISA CIENTÍFICA. Santa Maria, RS : UFSM, NTE,

Rani, R. Smulian, A. G. Greaves, D. R. Hogan, S. P. & Herbert, D. R. (2011). TGF-beta limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function. Eur J Immunol, 41(7), 2000–2009.

Robbins, C. (2012). Fundamentos de Patologia. Elsevier.

Rodríguez, M. M. Sánchez, B. P. Merlos, M. & Garzón, N. J. (2016). Endocannabinoid control of glutamate NMDA receptors: the therapeutic potential and consequences of dysfunction. Oncotarget, 7(34), 55840-55862.

Sedlak, J. & Lindsay, R. H. (1968). Estimation of total, proteinbound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem, 25(1), 192–205.

Silva, V. G. Silva, R. O. Damasceno SR, Carvalho, N. S. Prudêncio, R. S. Aragão, K. S. Guimarães, M. A. Campos, S. A. Véras, L. M. C. Godejohann, M. Leite, J. R. S. A. Barbosa, A. L. R. & Medeiros J. V. R. (2013). Anti-inflammatory and antinociceptive activity of epiisopiloturine, an imidazole alkaloid isolated from Pilocarpus microphyllus. Journal of natural products, 76(6), 1071–1077.

Storr, M. A. Keenan, C. M. Zhang, H. Patel, K. D. Makriyannis, A. & Sharkey, K. A. (2009). Activation of the cannabinoid 2 receptor (CB2) protects against experimental colitis. Inflammatory Bowel Diseases, 15(11), 1678–1685.

Tavares-Murta, B. M. de Resende, A. D. Cunha, F. Q. & Murta, E. F. C. (2008). Local profile of cytokines and nitric oxide in patients with bacterial vaginosis and cervical intraepithelial neoplasia. Eur J Obstet Gynecol Repro Biol, 138(1), 93–99.

Taylor, C. P. & Harris, E. W. (2020). Analgesia with gabapentin and pregabalin may involve N-methyl-D-aspartate receptors, neurexins, and thrombospondins. J Pharmacol Exp Ther, 374(1), 161–74.

Tewari-Singh, N. Rana, S. Gu, M. Pal, A. Orlicky, D. J. White, C. W. & Agarwal, R. (2009). Inflammatory Biomarkers of Sulfur Mustard Analog 2-Chloroethyl Ethyl Sulfide–Induced Skin Injury in SKH-1 Hairless Mice. Toxicological Sciences, 108(1), 194–206.

Verri, W. A. Jr. Souto, F. O. Vieira, S. M. Almeida, S. C. L. Fukada, S. Y. Xu, D. Alves-Filho, J. C. Cunha, T. M. Guerrero, A. T. G. Mattos-Guimaraes, R. B. Oliveira, F. R. Teixeira, M. M. Silva, J. S. McInnes, I. B. Ferreira, S. H. Louzada-Junior, P. Liew, F. Y. Cunha, F. Q. (2010). IL-33 induces neutrophil migration in rheumatoid arthritis and is a target of anti-TNF therapy. Ann. Rheum. Dis, 69(9), 1697−1703.

Witaicenis, A. Seito, L. N. da Silveir, C. A. de Almeida Jr, L. D. Luchini, A. C. Rodrigues-Orsi, P. Cestari, S. H. & Di Stasi L. C. (2014). Antioxidant and intestinal anti-inflammatory effects of plantderived coumarin derivatives. Phytomedicine, 21(3), 240–246.

Sałaga, M. Mokrowiecka, A. Zakrzewski, P. K. Cygankiewicz, A. Leishman, E. Sobczak, M. Zatorski, H. Małecka-Panas, E. Kordek, R. Storr, M. Krajewska, W. M. Bradshaw, H. B. &, J. (2014). Experimental colitis in mice is attenuated by changes in the levels of endocannabinoid metabolites induced by selective inhibition of fatty acid amide hydrolase (FAAH). J. Crohns Coliti, 8(9), 998–1009.

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Published

26/06/2021

How to Cite

BATISTA, J. A. .; MAGALHÃES, D. de A. .; SOUSA, S. G.; BRITO, T. V. .; MONTEIRO, C. E. S.; DUTRA, N. L. S.; PEREIRA, C. M. C.; LIMA, J. V. do N.; ALBUQUERQUE, I. F. de .; RODRIGUES, L. da R. .; FRANCO, Álvaro X. .; SILVA, F. R. P. da .; VASCONCELOS, D. F. P. .; BARBOSA, A. L. R. Gabapentin improves colonic inflammatory damage and oxidative stress on acetic acid-induced colitis independent of cannabinoid pathway. Research, Society and Development, [S. l.], v. 10, n. 7, p. e38510716693, 2021. DOI: 10.33448/rsd-v10i7.16693. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/16693. Acesso em: 26 apr. 2024.

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Health Sciences