Zhang Junhui, Zhang Hongyan, Guo Bao, Yang Jun, Yu Renxiang, Chen Wenxiu, Zhai Muxin, Yuhan Cao, Liu Yajing, Hong Qiang, Xie Fenfen
J Zhang, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
H Zhang, Department of Histology and Embryology, Anhui Medical University, Hefei, China.
Endocr Connect. 2024 Sep 1;13(12). doi: 10.1530/EC-24-0303.
The elevated level of hepatic oxidative stress (OS) in polycystic ovary syndrome (PCOS) is one of the important causes of liver abnormalities. Therefore, decreasing the level of hepatic OS in PCOS is beneficial to reduce the risk of PCOS-related liver diseases. Melatonin (MT), recognized as a potent antioxidant. Nevertheless, the efficacy of MT in alleviating hepatic OS associated with PCOS is yet to be established, and the precise mechanisms through which MT exerts its antioxidant effects remain to be fully elucidated. The aim of this study was to explore the potential mechanism by which MT reduces hepatic OS in PCOS. First, we detected elevated OS levels in the PCOS samples. Subsequently, with MT pretreatment, we discovered that MT could significantly diminish the levels of OS, liver triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)，while concurrently ameliorating mitochondrial structural damage in PCOS liver. Furthermore, we identified elevated autophagy levels in the liver of PCOS rats and an inhibition of the Keap1-Nrf2 pathway. Through MT pretreatment, the expression of LC3 was significantly decreased, while the Keap1-Nrf2 pathway was activated. Our study showed that MT could affect the Nrf2 pathway dependent on the P62/LC3 autophagy pathway, thereby attenuating hepatic OS in PCOS. These findings offer novel insights and research avenues for the study of PCOS-related liver diseases.
多囊卵巢综合征（PCOS）中肝脏氧化应激（OS）水平升高是肝脏异常的重要原因之一。因此，降低PCOS患者肝脏OS水平有利于降低PCOS相关肝脏疾病的风险。褪黑素（MT）是一种公认的强效抗氧化剂。然而，MT缓解PCOS相关肝脏OS的疗效尚未确定，MT发挥抗氧化作用的确切机制仍有待充分阐明。本研究的目的是探讨MT降低PCOS患者肝脏OS的潜在机制。首先，我们检测到PCOS样本中OS水平升高。随后，通过MT预处理，我们发现MT可以显著降低OS、肝脏甘油三酯（TG）、总胆固醇（TC）、丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平，同时改善PCOS肝脏中的线粒体结构损伤。此外，我们发现PCOS大鼠肝脏中的自噬水平升高，且Keap1-Nrf2通路受到抑制。通过MT预处理，LC3的表达显著降低，而Keap1-Nrf2通路被激活。我们的研究表明，MT可通过P62/LC3自噬途径影响Nrf2通路，从而减轻PCOS患者的肝脏OS。这些发现为PCOS相关肝脏疾病的研究提供了新的见解和研究途径。
