Abstract

OXIDATIVE STRESS-DRIVEN PATHOPHYSIOLOGY OF ENDOMETRIOSIS: INSIGHTS FROM 12Z CELL LINE MODELS AND EMERGING ANTIOXIDANT THERAPEUTIC STRATEGIES

Asmitha R. V., Maignanamoorthy V., Rajesh V., Anandhi B.*

Abstract

Endometriosis is a chronic estrogen-dependent condition where endometrial-like tissue (the tissue that lines the uterus) grows outside the cavity of the uterus, leading to chronic pelvic pain, infertility, inflammation, and a decrease in quality of life. The mechanisms of disease initiation and progression that have emerged are multifaceted including retrograde menstruation, iron overload, mitochondrial dysfunction, immune dysregulation, chronic inflammation, angiogenesis, epithelial–mesenchymal transition, and progesterone resistance with oxidative stress acting as a central pathogenic mechanism. The role of the 12Z endometriotic epithelial cell line in in vitro studies of oxidative stress-mediated mechanisms and evaluation of antioxidant therapeutics are emphasized. The molecular mechanisms of ROS and RNS induced lipid peroxidation, protein oxidation, DNA damage, activation of redox-sensitive signaling mechanisms, such as NF-κB, MAPK, PI3K/Akt, and VEGF-mediated angiogenesis are discussed in detail. Experimental induction of oxidative stress (such as hydrogen peroxide, tert-butyl hydroperoxide, menadione and hypoxia–reoxygenation, iron overload, and inflammatory stimuli) and commonly used analytical endpoints (cell viability, lactate dehydrogenase release, intracellular ROS, mitochondrial superoxide, TBARS/MDA, 4-HNE, antioxidant enzyme activity, cytokine profiling, apoptosis markers, qPCR, Western blotting, and immunofluorescence) are summarized. In addition, complementary non-hormonal strategies (such as the antioxidant compounds, curcumin, resveratrol, quercetin, epigallocatechin gallate (EGCG), N-acetylcysteine, and melatonin) are discussed for their therapeutic potential in decreasing oxidative damage, inhibiting inflammatory signaling, and for future personalized treatment of endometriosis. In summary, this review highlights oxidative stress as a potential therapeutic target and supports the use in the further investigation of mechanisms and the discovery of new antioxidant-based interventions.

Keywords: Endometriosis; oxidative stress; 12Z cell line; reactive oxygen species; inflammation; antioxidant therapy.