O ácido gama-linolênico interage com o canal de cálcio dependente de voltagem humano
aspectos no tratamento da mastalgia
DOI:
https://doi.org/10.56102/afmo.2025.388Palavras-chave:
Ácido gama-linolênico, Mastalgia, Analgésico, Modelagem de drogas, Canal de cálcio dependente de voltagemResumo
Objetivos: Avaliar a correlação do ácido gama-linolênico (GLA) com o CaV3.2 e comparar com a pregabalina (PGB), como perspectiva de elucidar o mecanismo de ação analgésica do GLA em casos de mastalgia. Métodos: Refere-se a uma pesquisa quantitativa e experimental, do tipo in silico, que empregou como moléculas ligantes o GLA e a PGB, e, como alvo proteico, o canal CaV3.2. Os experimentos de docagem molecular foram realizados no portal Dockthor e analisados pelo programa Chimera 1.14. Os resultados das simulações dos ligantes com o CaV3.2 foram organizados pelas afinidades de ligação (AL). Para comparação das AL, foi utilizado o teste “t” e foram considerados significantes valores de p < 0,05. Resultados e discussão: Após 1 milhão de simulações entre GLA e PGB com o CaV3.2, selecionaram-se os três melhores posicionamentos. Não houve diferença significante entre os valores de AL do GLA e da PGB (p = 0,15). Os ligantes se posicionaram dentro do poro do canal e estabelecendo ligações de hidrogênios com os mesmos resíduos de aminoácido e PGB apresentou interação com um outro a mais. Conclusão: O GLA é capaz de se ligar ao CaV3.2 de maneira semelhante ao bloqueador controle pregabalina. As interações químicas mostradas sugerem um possível bloqueio do canal, o que justificaria o efeito no controle da mastalgia pelo ácido gama-linolênico.
Referências
Olawaiye A, Withiam-Leitch M, Danakas G, Kahn K. Mastalgia: a review of management. J Reprod Med. 2005;50(12):933-9. Disponível em: https://www.researchgate.net/publication/7328732_Mastalgia_A_review_of_management
Smith RL, Pruthi S, Fitzpatrick LA. Evaluation and management of breast pain. Mayo Clin Proc. 2004;79(3):353-72. https://doi.org/10.4065/79.3.353
Grullon S, Bechmann S. Mastodynia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2022;32644675.
Dobryniewski J, Szajda SD, Waszkiewicz N, Zwierz K. Kwas gamma-linolenowy (GLA)— znaczenie terapeutyczne [The gamma-linolenic acid (GLA)—the therapeutic value]. Przegl Lek. 2007;64(2):100-2. Disponível em: https://www.researchgate.net/publication/5952444_The_gamma-linolenic_acid_GLA--the_therapeutic_value
Menke CH, et al. Rotinas em Mastologia. 1ª ed. Porto Alegre: Artes Médicas Sul; 2000;73.
Burbage J, Cameron L. An investigation into the prevalence and impact of breast pain, bra issues and breast size on female horse riders. J Sports Sci. 2017;35(11):1091-1097. https://doi.org/10.1080/02640414.2016.1210818
Functional nutrition and applicability of herbal medicines in the health of women with Premenstrual Syndrome: systematic review. Brazilian Journal of Health Review 2022;5(4):12766–12786. https://doi.org/10.34119/bjhrv5n4-067
Kapoor K, Huang Y-S. Gamma linolenic acid: an antiinflammatory omega-6 fatty acid. Current Pharmac Biotech 2006;7:531-534. https://doi.org/10.2174/138920106779116874
Zamponi GW, Striessnig J, Koschak A, Dolphin AC. The physiology, pathology, and pharmacology of voltage-gated calcium channels and their future therapeutic potential. Pharm. Rev. 2015;67(4):821–870. https://doi.org/10.1124/pr.114.009654
Choi S, Na HS, Kim J, Lee J, Lee S, Kim D, Park J, Chen CC, Campbell KP, Shin HS. Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels. Genes Brain Behav.2007;6(5):425–431. https://doi.org/10.1111/j.1601-183X.2006.00268.x
Talley EM, Cribbs LL, Lee JH, Daud A, Perez-Reyes E, Bayliss DA. Differential distribution of three members of a gene family encoding low voltage-activated (Ttype) calcium channels. J. Neurosci. 1999;19(6):1895–1911. https://doi.org/10.1523/jneurosci.19-06-01895.1999
Harding, E.K., Zamponi, G.W. Central and peripheral contributions of T-type calcium channels in pain. Mol Brain 15, 39 (2022). https://doi.org/10.1186/s13041-022-00923-w
Kamau PM, Li H, Yao Z, Han Y, Luo A, Zhang H, Boonyarat C, Yenjai C, Mwangi J, Zeng L, Yang S, Lai R, Luo L. Potent CaV3.2 channel inhibitors exert analgesic effects in acute and chronic pain models. Biomedicine & Pharmacotherapy 2022;153:113310. https://doi.org/10.1016/j.biopha.2022.113310
Jarvis MF, Scott VE, McGaraughty S, Chu KL, Xu J, Niforatos W, Milicic I, Joshi S, Zhang Q, Xia Z. A peripherally acting, selective T-type calcium channel blocker, ABT-639, effectively reduces nociceptive and neuropathic pain in rats, Biochem. Pharmacol. 2014;89(4):536–544. https://doi.org/10.1016/j.bcp.2014.03.015
Ziegler D, Duan WR, G. G, Thomas JW, Nothaft W. A randomized doubleblind, placebo-, and active-controlled study of T-type calcium channel blocker ABT-639 in patients with diabetic peripheral neuropathic pain. Pain 2015;156(10):2013–2020. https://doi.org/10.1097/j.pain.0000000000000263
Lee M. Z944: a first in class T-type calcium channel modulator for the treatment of pain. J. Peripher. Nerv. Syst. 2014;19(2):S11–S12. https://doi.org/10.1111/jns.12080_2
Snutch TP, Zamponi GW. Recent advances in the development of T-type calcium channel blockers for pain intervention. Br. J. Pharmacol. 2018;175(12):2375–2383. https://doi.org/10.1111/bph.13906
Asiamah I, Obiri SA, Tamekloe W, Armah FA, Borquaye LS. Applications of Molecular Docking in Natural Products-Based Drug Discovery. Scientific African 2023;S2468-2276. https://doi.org/10.1016/j.sciaf.2023.e01593
Teixeira LR, Silva Júnior JJ, Vieira PHS, Canto MVG, Figueirêdo AGM, Silva JLV. (2021). Tamoxifen inhibits the anion channel induced by Staphylococcus aureus α-hemolysin: electrophysiological and docking analysis. RSD [Internet]. 2021;10(2):e13010212326. https://doi.org/10.33448/rsd-v10i2.12326
Gentile F, Oprea TI, Tropsha A, Cherkasov A, (2023). Surely you are joking, Mr Docking! Chem. Soc. Rev. 2023;52:872–878. https://doi.org/10.1039/D2CS00948J
Sadybekov AV, Katritch V. Computational approaches streamlining drug discovery. Nature 2023;616:673–685. https://doi.org/10.1038/s41586-023-05905-z
Varela-Rial, A., Majewski, M., De Fabritiis, G., (2022). Structure based virtual screening: fast and slow. WIREs Comput. Mol. Sci. 2022;12:e1544. https://doi.org/10.1002/wcms.1544.
Bender BJ, Gahbauer S, Luttens A, Lyu J, Webb CM, Stein RM, Fink EA, Balius TE, Carlsson J, Irwin JJ, Shoichet BK. A practical guide to large-scale docking. Nature Protoc. 2021;16:4799–4832. https://doi.org/10.1038/s41596-021-00597-z
Guedes IA, Silva MMPS, Galheigo M, Krempser E, Magalhães CS, Barbosa HJC, Dardenne LE. DockThor-VS: A Free Platform for Receptor-Ligand Virtual Screening. Journal of Molecular Biology 2024;436(17):168548. https://doi.org/10.1016/j.jmb.2024.168548
Kataria K, Dhar A, Srivastava A, Kumar S, Goyal A. A Systematic Review of Current Understanding and Management of Mastalgia. Indian J Surg. 2014;76(3):217–222. https://doi.org/10.1007/s12262-013-0813-8
Liu ZL, Li L, Ma HL, Zhong QS, Ke JY, Zhang H. Mechanism of action of Zhishi Daozhi decoction in the treatment of diarrhea based on network pharmacology and molecular docking. Drug Combination Therapy 2023;5(1):1-8. https://doi.org/10.53388/DCT20230003
Du G, Qu X, Hu J, Zhang Y, Cai Y. Identification of Taohong Siwu Decoction in Treating Chronic Glomerulonephritis Using Network Pharmacology and Molecular Docking. Natural Product Communications 2022;17(11):1-12. https://doi.org/10.1177/1934578X221139966
Silva Júnior GJ, Arruda GEJ, Lira NBD, Lira NBD, Costa AEA, Morioka CY, Silva JLV. Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel Nav1.7. Rsd [Internet]. 2023;12(3):E30340292. https://doi.org/10.33448/Rsd-V12i3.40292
Harding EK, Zamponi GW. Central and peripheral contributions of T-type calcium channels in pain. Mol Brain. 2022;15(1):39. https://doi.org/10.1186/s13041-022-00923-w
Weiss N, Zamponi GW. (2020). Genetic T-type calcium channelopathies. Journal of Medical Genetics 2020;57(1):1–10. https://doi.org/10.1136/jmedgenet-2019-106163
Silva JLV, Leite AI, Ferreira EN, Silva FM, Pavin JP, Oliveira LC, Marcela Eduarda Leite ME, Araújo MV, Ferreira RN, Lamares RJTC, Melo LR. Gamma-linolenic acid interactions with the human voltage-gated sodium channel 1.7 by molecular docking: its role in the action mechanism on mastalgia. IOSR Journal Of Pharmacy And Biological Sciences 2023;18,6(3):33-37. DOI: 10.9790/3008-1806033337. Disponível em: https://www.iosrjournals.org/iosr-jpbs/papers/Vol18-issue6/Ser-3/G1806033337.pdf
Emery EE, Luiz AP, Wood JN. Nav1.7 and other voltage-gated sodium channels as drug targets for pain relief. Expert Opinion On Therapeutic Targets 2016;20(8): 975–983. http://dx.doi.org/10.1517/14728222.2016.1162295
Huang J, Fan X, Jin X, Lyu C, Guo Q, Liu T, Chen J, Davakan A, Lory P, Yan N. Structural basis for human Cav3.2 inhibition by selective antagonists. Cell Res 34, 440–450 (2024). https://doi.org/10.1038/s41422-024-00959-8
Taylor CP. Mechanisms of analgesia by gabapentin and pregabalin--calcium channel alpha2-delta [Cavalpha2-delta] ligands. Pain 2009;142(1-2):13-6. https://doi.org/10.1016/j.pain.2008.11.019
Calandre EP, Rico-Villademoros F, Slim M. Alpha2delta ligands, gabapentin, pregabalin and mirogabalin: a review of their clinical pharmacology and therapeutic use. Expert Rev Neurother. 2016;16(11):1263-1277. https://doi.org/10.1080/14737175.2016.1202764
Onakpoya IJ, Thomas ET, Lee JJ, Goldacre B, Heneghan CJ. Benefits and harms of pregabalin in the management of neuropathic pain: a rapid review and meta-analysis of randomised clinical trials. BMJ Open. 2019;9(1):e023600. https://doi.org/10.1136/bmjopen-2018-023600
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2025 Gidelson José da Silva Júnior, Gisele Evelin de Jesus Arruda, Ana Carolina de Oliveira Aguiar, Lais Cristhinne Sabino Gondim, Lise Reis Melo, Joelmir Lucena Veiga da Silva
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Esta licença permite que outros distribuam, remixem, adaptem e desenvolvam seu trabalho, mesmo comercialmente, desde que creditem a revista pela criação original.
