Piroglutamato na Síndrome do Ovário Poliquístico (SOP)
O piroglutamato, também conhecido como 5-oxoprolina, é um metabolito que tem ganhado destaque pelo seu possível papel na fisiopatologia da síndrome do ovário poliquístico (SOP). A SOP é uma desordem endócrina complexa, caracterizada por hiperandrogenismo, disfunção ovulatória e morfologia ovariana poliquística, que afeta uma proporção significativa de mulheres em idade reprodutiva (Marques et al., 2017; Aversa et al., 2020). A interação entre o stress oxidativo, resistência à insulina e disfunções metabólicas na SOP está bem documentada, e o piroglutamato pode emergir como um biomarcador relevante neste contexto.
Stress Oxidativo e o Papel do Piroglutamato
Pesquisas indicam que mulheres com SOP frequentemente apresentam níveis elevados de stress oxidativo, o que pode levar à depleção de glutationa, um antioxidante essencial no organismo. Essa depleção resulta no acúmulo de metabolitos como o piroglutamato (Spinedi & Cardinali, 2018; Zhong et al., 2022). A relação entre o stress oxidativo e o piroglutamato na SOP é particularmente importante, dado que o stress oxidativo está implicado no desenvolvimento da resistência à insulina, um dos principais traços da síndrome (Ishrat et al., 2021). Níveis elevados de piroglutamato podem refletir a tentativa do organismo de combater os danos oxidativos, indicando um estado de sofrimento metabólico característico da SOP.
Influência da Dieta e Estilo de Vida
Estudos mostram que os níveis de piroglutamato podem ser influenciados por fatores dietéticos e escolhas de estilo de vida, que desempenham um papel crucial no manejo dos sintomas da SOP. Por exemplo, dietas ricas em antioxidantes podem ajudar a mitigar o stress oxidativo e, consequentemente, a reduzir os níveis de piroglutamato (Kuntal et al., 2021). Além disso, intervenções que visam melhorar a sensibilidade à insulina, como o controlo de peso e a prática de atividade física, podem impactar positivamente as vias metabólicas relacionadas ao piroglutamato (Camili, 2023).
Impactos na Saúde Reprodutiva
O papel do piroglutamato na SOP vai além das perturbações metabólicas, tendo também implicações na saúde reprodutiva. O ambiente oxidativo associado a níveis elevados de piroglutamato pode afetar negativamente a função ovariana e o desenvolvimento folicular, contribuindo para anovulação e infertilidade (MAAMOUN & M.D.*, 2022). Compreender as vias metabólicas que envolvem o piroglutamato pode fornecer novas perspetivas para estratégias terapêuticas na gestão da SOP, particularmente no combate ao stress oxidativo e à resistência à insulina, que estão na base de muitos dos seus sintomas.
Conclusão
O piroglutamato surge como um metabolito significativo no contexto da síndrome do ovário poliquístico, refletindo a interação complexa entre o stress oxidativo, resistência
à insulina e saúde reprodutiva. São necessários mais estudos para esclarecer o seu papel exato e o potencial como biomarcador ou alvo terapêutico na gestão da SOP.
References:
A.Ali, H. (2015). Hormonal profile and oxidative stress are directed by anthropometric measures in polycystic ovary syndrome. Al-Kufa University Journal for Biology, 7(3), 55-67. https://doi.org/10.36320/ajb/v7.i3.8072
Aversa, A., Vignera, S., Rago, R., Gambineri, A., Nappi, R., Calogero, A., … & Ferlin, A. (2020). Fundamental concepts and novel aspects of polycystic ovarian syndrome: expert consensus resolutions. Frontiers in Endocrinology, 11. https://doi.org/10.3389/fendo.2020.00516
Azziz, R., Carmina, E., Chen, Z., Dunaif, A., Laven, J., Legro, R., … & Yildiz, B. (2016). Polycystic ovary syndrome. Nature Reviews Disease Primers, 2(1). https://doi.org/10.1038/nrdp.2016.57
Bernardo-Bermejo, S., Sánchez-López, E., Tan, L., Benito-Martínez, S., Jiang, Z., Castro-Puyana, M., … & Marina, M. (2021). Exploratory metabolomic analysis based on reversed-phase liquid chromatography–mass spectrometry to study an in vitro model of hypoxia-induced metabolic alterations in hk-2 cells. International Journal of Molecular Sciences, 22(14), 7399. https://doi.org/10.3390/ijms22147399
Bhide, A., Tailor, V., & Khullar, V. (2020). Interstitial cystitis/bladder pain syndrome and recurrent urinary tract infection and the potential role of the urinary microbiome. Post Reproductive Health, 26(2), 87-90. https://doi.org/10.1177/2053369120936426
Bhide, A., Tailor, V., & Khullar, V. (2020). Interstitial cystitis/bladder pain syndrome and recurrent urinary tract infection and the potential role of the urinary microbiome. Post Reproductive Health, 26(2), 87-90. https://doi.org/10.1177/2053369120936426
Camili, F. (2023). Oncostatin m levels are associated with the pathogenesis of polycystic ovary syndrome and its metabolic complications.. https://doi.org/10.20944/preprints202311.1648.v1
Choi, H., Lee, K., & Kim, D. (2021). The microbiome’s function in disorders of the urinary bladder. Applied Microbiology, 1(3), 445-459. https://doi.org/10.3390/applmicrobiol1030029
Gamarra, Y., Santiago, F., Molina-López, J., Castaño, J., Herrera-Quintana, L., Domínguez, Á., … & Planells, E. (2019). Pyroglutamic acidosis by glutathione regeneration blockage in critical patients with septic shock. Critical Care, 23(1). https://doi.org/10.1186/s13054-019-2450-5
Gasiorek, M., Hsieh, M., & Forster, C. (2019). Utility of dna next-generation sequencing and expanded quantitative urine culture in diagnosis and management of chronic or persistent lower urinary tract symptoms. Journal of Clinical Microbiology, 58(1). https://doi.org/10.1128/jcm.00204-19
Gunn, J. (2020). An analysis of biomarkers in patients with
chronic pain. Pain Physician, 1;23(1;1), E41-E49. https://doi.org/10.36076/ppj.2020/23/e41
Hakkola, M., Vehviläinen, P., Muotka, J., Tejesvi, M., Pokka, T., Vähäsarja, P., … & Tapiainen, T. (2023). Cranberry‐lingonberry juice affects the gut and urinary microbiome in children ‐ a randomized controlled trial. Apmis, 131(3), 112-124. https://doi.org/10.1111/apm.13292
Hakkola, M., Vehviläinen, P., Muotka, J., Tejesvi, M., Pokka, T., Vähäsarja, P., … & Tapiainen, T. (2023). Cranberry‐lingonberry juice affects the gut and urinary microbiome in children ‐ a randomized controlled trial. Apmis, 131(3), 112-124. https://doi.org/10.1111/apm.13292
Han, H. and Lee, J. (2022). Microbiome analysis using next-generation sequencing in urinary tract infections. Urogenital Tract Infection, 17(1), 1-7. https://doi.org/10.14777/uti.2022.17.1.1
Ishrat, S., Hossain, M., & Biswas, S. (2021). Insulin resistance in relation to clinical, endocrine and metabolic profile of infertile women with polycystic ovary syndrome. Bangabandhu Sheikh Mujib Medical University Journal, 14(1), 1-6. https://doi.org/10.3329/bsmmuj.v14i1.50989
Ishrat, S., Hossain, M., & Biswas, S. (2021). Insulin resistance in relation to clinical, endocrine and metabolic profile of infertile women with polycystic ovary syndrome. Bangabandhu Sheikh Mujib Medical University Journal, 14(1), 1-6. https://doi.org/10.3329/bsmmuj.v14i1.50989
Johnson, J., Delaney, L., Ojha, V., Rudraraju, M., Hintze, K., Siddiqui, N., … & Sysoeva, T. (2022). Commensal urinary lactobacilli inhibit major uropathogens in vitro with heterogeneity at species and strain level. Frontiers in Cellular and Infection Microbiology, 12. https://doi.org/10.3389/fcimb.2022.870603
Kuntal, C., Vyas, J., Chaudhary, A., Hemani, S., & Rajoria, L. (2021). A study of metabolic syndrome in women with polycystic ovary syndrome at tertiary care center. International Journal of Reproduction Contraception Obstetrics and Gynecology, 10(6), 2427. https://doi.org/10.18203/2320-1770.ijrcog20212187
MAAMOUN, M. and M.D.*, C. (2022). Therapeutic effect of quercetin in letrozole induced polycystic ovary syndrome in rat model. The Medical Journal of Cairo University, 90(12), 2777-2799. https://doi.org/10.21608/mjcu.2022.296228
Marques, A., Silva, C., Colmonero, S., & Andrade, P. (2017). Diabetes mellitus and polycystic ovary syndrome: beyond a dermatological problem. Diabetes Case Reports, 01(03). https://doi.org/10.4172/2572-5629.1000113
Meštrović, T., Matijašić, M., Perić, M., Paljetak, H., Barešić, A., & Verbanac, D. (2020). The role of gut, vaginal, and urinary microbiome in urinary tract infections: from bench to bedside. Diagnostics, 11(1), 7. https://doi.org/10.3390/diagnostics11010007
Meštrović, T., Matijašić, M., Perić, M., Paljetak, H., Barešić, A., & Verbanac, D. (2020). The role of gut, vaginal, and urinary microbiome in urinary tract infections: from bench to bedside. Diagnostics, 11(1), 7. https://doi.org/10.3390/diagnostics11010007
Mohmmed, A., Awad, N., & Al–Fartosy, A. (2019). Study of trace elements selenium, copper, zinc and manganese level in polycystic ovary syndrome (pcos). International Journal for Research in Applied Sciences and Biotechnology, 06(06), 16-22. https://doi.org/10.31033/ijrasb.6.6.4
Muhammad, B. (2020). Characteristics and risk factors for polycystic ovarian syndrome among females. Kurdistan Journal of Applied Research, 5(1), 200-209. https://doi.org/10.24017/science.2020.14
Murgia, F., Lorefice, L., Noto, A., Spada, M., Frau, J., Fenu, G., … & Cocco, E. (2023). Metabolomic changes in patients affected by multiple sclerosis and treated with fingolimod. Metabolites, 13(3), 428. https://doi.org/10.3390/metabo13030428
Pandey, S., Siddiqui, M., Trigun, S., Azim, A., & Sinha, N. (2022). Gender-specific association of oxidative stress and immune response in septic shock mortality using
nmr-based metabolomics. Molecular Omics, 18(2), 143-153. https://doi.org/10.1039/d1mo00398d
Pearce, M., Hilt, E., Rosenfeld, A., Zilliox, M., Thomas‐White, K., Fok, C., … & Wolfe, A. (2014). The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. Mbio, 5(4). https://doi.org/10.1128/mbio.01283-14
Piras, C., Conte, S., Pibiri, M., Rao, G., Muntoni, S., Leoni, V., … & Atzori, L. (2020). Metabolomics and psychological features in fibromyalgia and electromagnetic sensitivity. Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-76876-8
Pérez-Carrasco, V., Soriano‐Lerma, A., Soriano, M., Gutiérrez‐Fernández, J., & García‐Salcedo, J. (2021). Urinary microbiome: yin and yang of the urinary tract. Frontiers in Cellular and Infection Microbiology, 11. https://doi.org/10.3389/fcimb.2021.617002
Pérez-Carrasco, V., Soriano‐Lerma, A., Soriano, M., Gutiérrez‐Fernández, J., & García‐Salcedo, J. (2021). Urinary microbiome: yin and yang of the urinary tract. Frontiers in Cellular and Infection Microbiology, 11. https://doi.org/10.3389/fcimb.2021.617002
Sengupta, P. (2024). Polycystic ovary syndrome (pcos) and oxidative stress. JIST, 12(3). https://doi.org/10.62110/sciencein.jist.2024.v12.752
Shah, N., Allegretti, A., Nigwekar, S., Kalim, S., Zhao, S., Lelouvier, B., … & Fasano, A. (2019). Blood microbiome profile in ckd. Clinical Journal of the American Society of Nephrology, 14(5), 692-701. https://doi.org/10.2215/cjn.12161018
Spinedi, E. and Cardinali, D. (2018). The polycystic ovary syndrome and the metabolic syndrome: a possible chronobiotic-cytoprotective adjuvant therapy. International Journal of Endocrinology, 2018, 1-12. https://doi.org/10.1155/2018/1349868
Usta, A., Avcı, E., Bülbül, Ç., Kadı, H., & Adalı, E. (2018). The monocyte counts to hdl cholesterol ratio in obese and lean patients with polycystic ovary syndrome. Reproductive Biology and Endocrinology, 16(1). https://doi.org/10.1186/s12958-018-0351-0
Venkataraman, S., Regone, R., Ammar, H., & Govindu, R. (2019). Pyroglutamic acidemia: an underrecognized and underdiagnosed cause of high anion gap metabolic acidosis – a case report and review of literature. Cureus. https://doi.org/10.7759/cureus.5229
Wu, P., Yang, C., Zhao, J., Zhang, G., Chen, J., Wang, J., … & Zhang, H. (2017). Urinary microbiome and psychological factors in women with overactive bladder. Frontiers in Cellular and Infection Microbiology, 7. https://doi.org/10.3389/fcimb.2017.00488
Wu, P., Yang, C., Zhao, J., Zhang, G., Chen, J., Wang, J., … & Zhang, H. (2017). Urinary microbiome and psychological factors in women with overactive bladder. Frontiers in Cellular and Infection Microbiology, 7. https://doi.org/10.3389/fcimb.2017.00488
Zampini, A., Nguyen, A., Rose, E., Monga, M., & Miller, A. (2019). Defining dysbiosis in patients with urolithiasis. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-41977-6
Zhong, P., Guan, B., Lin, Y., & Zhang, S. (2022). Changes in inflammatory factors, oxidative stress, glucose and lipid metabolism, and insulin resistance in patients with polycystic ovary syndrome. Cellular and Molecular Biology, 67(5), 45-50. https://doi.org/10.14715/cmb/2021.67.5.6
Zhong, P., Guan, B., Lin, Y., & Zhang, S. (2022). Changes in inflammatory factors, oxidative stress, glucose and lipid metabolism, and insulin resistance in patients with polycystic ovary syndrome. Cellular and Molecular Biology, 67(5), 45-50. https://doi.org/10.14715/cmb/2021.67.5.6
Łopacińska, O. (2024). Effects of antioxidant supplementation for polycystic ovary syndrome. Journal of Education Health and Sport, 61, 50695. https://doi.org/10.12775/jehs.2024.61.50695
