Melatonina e endometriose: bases bioquímicas de uma relação potencialmente terapêutica

Mariana Luiza de Paula Pessoa, Rebeca Amanda Rodrigues Costa, Fabiano Gomes Batista, Maria Clara Moreira de Oliveira, Rafael Máximo de Barros Canoza, Marcos Tulio Alves Rocha, Marcos Túlio Alves Da Rocha
In: Brazilian Journal of Health Review · 2023 · vol. 6(6) , pp. 30070–30089 · doi:10.34119/bjhrv6n6-268 · W4389270578
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This review found that melatonin treatment in endometriosis models reduced lesion volume and pain, modulated inflammatory and apoptotic pathways, and altered matrix metalloproteinases and cyclooxygenase-2.

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This paper is a narrative review that examines melatonin as a potentially therapeutic agent for endometriosis, synthesizing 16 experimental studies across rodents, humans, and human cell culture. Across these studies, melatonin exposure is associated with reduced endometriotic lesion volume, improved histopathologic scores, and modulation of oxidative-stress and inflammation pathways, including increased antioxidant enzymes such as superoxide dismutase and catalase, as well as regulation of matrix metalloproteinases, cyclooxygenase-2, and VEGF-related signaling. Additional reported effects include changes in apoptotic pathways, epithelial–mesenchymal transition markers, cellular senescence, brain-derived neurotrophic factor, and reduced pain scores. The paper’s main caveat is that it aggregates heterogeneous experimental evidence and does not provide new controlled clinical efficacy data; its conclusions therefore depend on the quality and comparability of included studies. This paper is centrally about endometriosis — it focuses on melatonin’s biochemical mechanisms and reported effects relevant to treating endometriotic lesions.

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Abstract

A endometriose, doença inflamatória crônica dependente de estrogênio na presença de tecido endometrial ectópico associado a dor e infertilidade, tem sido referida pelo comprometimento da qualidade de vida de mulheres em idade reprodutiva. Trata-se de um tecido com características semelhantes às de malignidades, de etiologia multifatorial e que se manifesta de forma heterogênea. Seu tratamento, baseado no uso de análogos do hormônio liberador de gonadotrofina, supressão da ovulação, uso de anti-inflamatórios não esteroides e intervenções cirúrgicas, ainda constitui um desafio. O hormônio melatonina, por sua vez, secretado, principalmente, pela glândula pineal, tem sido estudado por seu potencial terapêutico mediado por suas funções antioxidantes, anti-inflamatórias e analgésicas para o tratamento dessas lesões. Esta revisão objetiva discorrer sobre potencial terapêutico da melatonina no tratamento da endometriose e expor os principais mecanismos bioquímicos descritos. Nossos resultados incluíram 16 artigos experimentais realizados em roedores, humanos e em cultura de células humanas e elucidaram redução no volume das lesões, melhorias nos escores histopatológicos, modulações de enzimas envolvidas na eliminação de espécies reativas de oxigênio, como superóxido dismutase e catalase, além da regulação de metaloproteinases da matriz, cicloxigenase-2 e fator de crescimento vascular derivado do endotélio, como principais efeitos terapêutico da melatonina. Seu uso ainda foi associado à modulação de vias apoptóticas, marcadores de transição epitélio mesenquimal, senescência celular, fator neurotrófico derivado do cérebro e redução nos escores de dor. Concluímos haver um potencial terapêutico no uso de melatonina para o tratamento dessas lesões, o que demanda maiores investigações.
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Melatonina e endometriose: bases bioquímicas de uma relação potencialmente terapêutica DOI: https://doi.org/10.34119/bjhrv6n6-268Keywords: endometriose, melatonina, etiologia, fisiopatologia, tratamentoAbstract A endometriose, doença inflamatória crônica dependente de estrogênio na presença de tecido endometrial ectópico associado a dor e infertilidade, tem sido referida pelo comprometimento da qualidade de vida de mulheres em idade reprodutiva. Trata-se de um tecido com características semelhantes às de malignidades, de etiologia multifatorial e que se manifesta de forma heterogênea. Seu tratamento, baseado no uso de análogos do hormônio liberador de gonadotrofina, supressão da ovulação, uso de anti-inflamatórios não esteroides e intervenções cirúrgicas, ainda constitui um desafio. O hormônio melatonina, por sua vez, secretado, principalmente, pela glândula pineal, tem sido estudado por seu potencial terapêutico mediado por suas funções antioxidantes, anti-inflamatórias e analgésicas para o tratamento dessas lesões. Esta revisão objetiva discorrer sobre potencial terapêutico da melatonina no tratamento da endometriose e expor os principais mecanismos bioquímicos descritos. Nossos resultados incluíram 16 artigos experimentais realizados em roedores, humanos e em cultura de células humanas e elucidaram redução no volume das lesões, melhorias nos escores histopatológicos, modulações de enzimas envolvidas na eliminação de espécies reativas de oxigênio, como superóxido dismutase e catalase, além da regulação de metaloproteinases da matriz, cicloxigenase-2 e fator de crescimento vascular derivado do endotélio, como principais efeitos terapêutico da melatonina. Seu uso ainda foi associado à modulação de vias apoptóticas, marcadores de transição epitélio mesenquimal, senescência celular, fator neurotrófico derivado do cérebro e redução nos escores de dor. Concluímos haver um potencial terapêutico no uso de melatonina para o tratamento dessas lesões, o que demanda maiores investigações. References VIGANÒ, Paola et al. Endometriosis: epidemiology and aetiological factors. Best practice & research Clinical obstetrics & gynaecology, v. 18, n. 2, p. 177-200, 2004. BELLELIS, Patrick et al. Aspectos epidemiológicos e clínicos da endometriose pélvica: uma série de casos. Revista da Associação Médica Brasileira, v. 56, n. 4, p. 467-471, 2010. ROLLA, Edgardo. Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment. F1000Research, v. 8, 2019. NANDA, Amalesh et al. Cytokines, angiogenesis, and extracellular matrix degradation are augmented by oxidative stress in endometriosis. 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