Evaluation of the anti-ulcerative effects of lacosamide in a rat model of acetic acid-induced colitis

Mohsen Minaiyan, Niloufar Mottaghi

Abstract


Background and purpose: Colitis is a type of inflammatory bowel disease (IBD) with an unknown and complex etiology. Lacosamide is a known antiepileptic drug for which anti-inflammatory effects have been reported. This study investigates the ameliorative effects of lacosamide on acetic acid-induced colitis in rats.

Experimental approach: Male Wistar rats were divided into different interventional groups, including normal and control colitis groups (normal saline, 5 mL/kg), two colitis groups (dexamethasone, 1 mg/kg) and mesalazine (100 mg/kg), four colitis groups received oral lacosamide (10, 20, or 40 mg/kg), or lacosamide enema (10 mg/kg). The treatments were conducted for five days following disease induction by acetic acid (3.5%, 2 mL). Colitis indices in tissue samples, as well as biochemical factors such as myeloperoxidase (MPO), malondialdehyde (MDA), and ferric reducing antioxidant power (FRAP), were assessed.

Findings/Results: The trend of body weight drop was stopped by using lacosamide. Colon weight as well as ulcer index significantly decreased in the groups that received lacosamide (10-40 mg/kg via oral or rectal) compared to the control group. Histological findings showed that lacosamide (10 and 20 mg/kg via oral and enema) reduced inflammation markers and tissue damage while causing tissue regeneration. Levels of MDA and MPO significantly decreased while FRAP increased in lacosamide (10 and 20 mg/kg) groups, both oral and via enema.

Conclusion and implications: Findings highlight the potential of lacosamide as an effective treatment in reducing inflammation and promoting ulcer healing. However, further studies are needed to elucidate the precise mechanisms of lacosamide's anti-inflammatory effects and to confirm these results in human disease.

 


Keywords


Acetic acid; Inflammation; Lacosamide; Rats; Ulcerative colitis.

Full Text:

PDF

References


Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative Colitis. Lancet. 2017;389:1756-1770.DOI: 10.1016/S0140-6736(16)32126-2.

Aslam N, Lo SW, Sikafi R, Barnes T, Segal J, Smith PJ, et al. A review of the therapeutic management of ulcerative colitis. Therap Adv Gastroenterol. 2022;15:138160,1-21.DOI: 10.1177/17562848221138160.

Elhag DA, Kumar M, Saadaoui M, Akobeng AK, Al-Mudahka F, Elawad M, et al. Inflammatory bowel disease treatments and predictive biomarkers of therapeutic response. Int J Mol Sci. 2022;23:6966,1-25.DOI: 10.3390/ijms23136966.

Black J, Sweeney L, Yuan Y, Singh H, Norton C, Czuber-Dochan W. Systematic review: the role of psychological stress in inflammatory bowel disease. Aliment Pharmacol Ther. 2022;56(8): 1235-1249.DOI: 10.1111/apt.17202.

Kurina LM, Goldacre MJ, Yeates D, Gill LE. Depression and anxiety in people with inflammatory bowel disease. J Epidemiol Community Health.2001;55(10):716-720.DOI: 10.1136/jech.55.10.716.

Mikocka-Walus AA, Gordon AL, Stewart BJ, Andrews JM. The role of antidepressants in the management of inflammatory bowel disease (IBD): a short report on a clinical case-note audit. J Psychosom Res. 2012;72(2):165-167.DOI: 10.1016/j.jpsychores.2011.06.006.

Najafi A, Motaghi E, Hosseini MJ, Ghasemi-Pirbaluti M. The effect of sodium valproate on acetic acid-induced colitis in rats. Inflammopharmacolog. 2017;25(1):137-145.DOI: 10.1007/s10787-016-0304-1.

Silva I, Mendes P, Guerra S, Pinto R, Mateus V. Anti-inflammatory effect of topiramate in a chronic model of TNBS-induced colitis. Int J Mol Sci. 2022;23(16):9127,1-12.DOI: 10.3390/ijms23169127.

Amirshahrokhi K, Imani M. Levetiracetam attenuates experimental ulcerative colitis through promoting Nrf2/HO-1 antioxidant and inhibiting NF-κB, proinflammatory cytokines and iNOS/NO pathways. Int Immunopharmacol. 2023;119:110165.DOI: 10.1016/j.intimp.2023.110165.

Motavallian A, Bouzari S, Zamani E, Karimian P, Dabirian S, Molavi M, et al. An investigation of the anti-inflammatory effects of gabapentin on acetic acid-induced colitis in rats. Mol Biol Rep. 2021;48(4):3423-3430.DOI: 10.1007/s11033-021-06357-2.

Motavallian A, Zamani E, Bouzari S, Rezaeyan F, Karimian P, Evazalipour M. Anti-inflammatory effect of pregabalin on acetic acid-induced colitis in the rats. Res Pharm Sci. 2021;17(1):35-42.DOI: 10.4103/1735-5362.329924.

Cawello W. Clinical pharmacokinetic and pharmacodynamic profile of lacosamide. Clin Pharmacokinet. 2015;54(9):901-914.DOI: 10.1007/s40262-015-0276-0.

Beyreuther BK, Freitag J, Heers C, Krebsfanger N, Scharfenecker U, Stohr T. Lacosamide: a review of preclinical properties. CNS Drug Rev. 2007;13(1):21-42.DOI: 10.1111/j.1527-3458.2007.00001.x.

Halford JJ, Lapointe M. Clinical perspectives on lacosamide. Epilepsy Curr.2009;9(1):19,1-9.DOI: 10.1111/j.1535-7511.2008.01273.x.

Choi HY, Park JH, Chen BH, Shin BN, Lee YL, Kim IH, et al. Increases of catalase and glutathione peroxidase expressions by lacosamide pretreatment contributes to neuroprotection against experimentally induced transient cerebral ischemia. Neurochem Res.2016;41(9):2380-2390.DOI: 10.1007/s11064-016-1951-8.

Beyreuther B, Callizot N, Stohr T. Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain. Arthritis Res Ther. 2007;9(1):R14,1-8.DOI: 10.1186/ar2121.

Jalalipour M, Yegdaneh A, Talebi A, Minaiyan M. Salvia officinalis leaf extracts protect against acute colitis in rats. Res Pharm Sci. 2022;17(4):350-359.DOI: 10.4103/1735-5362.350236.

Stohr T, Krause E, Selve N. Lacosamide displays potent antinociceptive effects in animal models for inflammatory pain. Eur J Pain. 2006;10(3):241-249.DOI:10.1016/j.ejpain.2005.04.002.

Minaiyan M, Abolhasani S, Sima S, Yegdaneh A. Effect of Tamarindus indica L. fruit pulp and seed extracts on experimental ulcerative colitis in rats. Res Pharm Sci. 2024;19(3):276-286.DOI: 10.4103/RPS.RPS_131_23.

Minaiyan M, Asghari G, Taheri D, Saeidi M, Nasr-Esfahani S. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats. Avicenna J Phytomed. 2014;4(2):127-136.PMID: 25050310.

Dalayeli N, Hajhashemi V, Talebi A, Minaiyan M. Investigating the impact of selected B vitamins (B1, B2, B6, and B12) on acute colitis induced experimentally in rats. Int J Prev Med.2024;15:61,1-8.DOI: 10.4103/ijpvm.ijpvm_232_23.

El-Guourrami O, Elbouny H, Benlabchir AA, Drioua S, Ouahzizi B, Alem Ch, et al. Antioxidant activity, analgesic activity, and phytochemical analysis of Ammimajus (L.) extracts. Int J Sec Metabol. 2023;10:23-37.DOI: 10.21448/ijsm.1139246.

Subramanian S, Du C, Tan XD. Can rodent model of acetic acid-induced colitis be used to study the pathogenesis of colitis-associated intestinal fibrosis? J Invest Surg. 2022;35(1):223-224.DOI: 10.1080/08941939.2020.1821845.

Yu YR, Rodriguez JR. Clinical presentation of Crohn's, ulcerative colitis, and indeterminate colitis: symptoms, extraintestinal manifestations, and disease phenotypes. Semin Pediatr Surg. 2017;26(6):349-355.DOI: 10.1053/j.sempedsurg.2017.10.003.

Pacheco RG, Esposito CC, Müller LC, Castelo-Branco MT, Quintella LP, Chagas VL, et al. Use of butyrate or glutamine in enema solution reduces inflammation and fibrosis in experimental diversion colitis. World J Gastroenterol. 2012;18(32):4278-4287.DOI: 10.3748/wjg.v18.i32.4278.

Hou L, Peng B, Zhang D, Yang J, Wang Y, Tong L, et al. Clinical efficacy and safety of lacosamide as an adjunctive treatment in adults with refractory epilepsy. Front Neurol. 2021;12:712717,1-11.DOI: 10.3389/fneur.2021.712717.

Yang C, Peng Y, Zhang L, Zhao L. Safety and tolerability of lacosamide in patients with epilepsy: a systematic review and meta-analysis. Front Pharmacol. 2021;12:694381,1-12.DOI: 10.3389/fphar.2021.694381.

Nguelefack-Mbuyo EP, Peyembouo FP, Fofié CK, Nguelefack TB. Dose-dependent and time-dependent metabolic, hemodynamic, and redox disturbances in dexamethasone-treated Wistar rats. J Basic Clin Physiol Pharmacol. 2022;33(4):457-469.DOI: 10.1515/jbcpp-2020-0365.

Fornaro R, Actis GC, Caviglia GP, Pitoni D, Ribaldone DG. Inflammatory bowel disease: role of vagus nerve stimulation. J Clin Med. 2022;11(19):5690,1-10.DOI: 10.3390/jcm11195690.

Varzandeh R, Khezri MR, Esmaeilzadeh Z, Jafari A, Ghasemnejad-Berenji M. Protective effects of topiramate on acetic acid-induced colitis in rats through the inhibition of oxidative stress. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(2):1141-1149.DOI: 10.1007/s00210-023-02677-1.

Mahdavi NS, Talebi A, Minaiyan M. Ameliorative effect of galantamine on acetic acid-induced colitis in rats. Res Pharm Sci. 2019;14(5):391-399.DOI: 10.4103/1735-5362.268199.

Agarwal S, Vyas P, Nirwan N, Vohora D. Effect of lacosamide on neuroinflammation-mediated seizures comorbid with depression in C57BL/6 mice- role of kynurenine pathway. Epilepsy Behav. 2021;123:108262,13-21.DOI: 10.1016/j.yebeh.2021.108262.

Corvace F, Faustmann TJ, Faustmann PM, Ismail FS. Anti-inflammatory properties of lacosamide in an astrocyte-microglia co-culture model of inflammation. Eur J Pharmacol. 2022;915:17469,1-9.DOI: 10.1016/j.ejphar.2021.174696.

Hearn L, Derry S, Moore RA. Lacosamide for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2012;2012(2):1-34.DOI: 10.1002/14651858.


Refbacks

  • There are currently no refbacks.


Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.