SUBMICROSCOPIC CHANGES IN THE GASTRIC MUCOSA IN METABOLIC SYNDROME: SEXUAL DIMORPHISM AND ANTIOXIDANT PROTECTION

Metabolic syndrome (MetS) constitutes a complex cluster of interconnected risk factors, including central obesity, insulin resistance, dyslipidemia, hypertension, and hyperglycemia, which synergistically heighten the susceptibility to cardiovascular diseases, type 2 diabetes mellitus, and various gastrointestinal disorders. This extensive review delves deeply into the submicroscopic, or ultrastructural, modifications occurring within the gastric mucosa in the context of MetS, placing a strong emphasis on the influences of sexual dimorphism and the protective mechanisms afforded by antioxidant systems. Sourced from prestigious, high-impact databases such as PubMed, ScienceDirect, MDPI, and PMC, this analysis integrates a broad spectrum of recent studies to elucidate how oxidative stress—stemming from excessive reactive oxygen species (ROS) production, mitochondrial dysfunction, and perturbations in gut microbiota composition—precipitates epithelial cell damage, inflammatory cascades, and compromised mucosal integrity. Sexual dimorphism plays a pivotal role, with sex hormones such as estrogens and androgens modulating these pathological processes differentially between males and females. Estrogens, prevalent in premenopausal women, exert anti-inflammatory and antioxidant effects, fostering a more resilient gut microbiome that mitigates oxidative burden and preserves ultrastructural features like mitochondrial morphology and endoplasmic reticulum (ER) architecture. In contrast, androgens in males often exacerbate dysbiosis, leading to heightened insulin resistance, chronic low-grade inflammation (LGCI), and more severe submicroscopic alterations, including vacuolization, cristae disruption in mitochondria, and dilation of the ER. These differences are further accentuated in conditions like menopause or andropause, where hormonal shifts align female vulnerabilities closer to those observed in males. Antioxidant protection emerges as a critical countermeasure, encompassing enzymatic defenses such as superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), and non-enzymatic agents like glutathione (GSH) and vitamins. The gut microbiota contributes by generating short-chain fatty acids (SCFAs) that enhance barrier function and quench ROS, yet MetS-induced dysbiosis impairs this synergy, amplifying damage. Ultrastructural investigations employing transmission electron microscopy (TEM) and scanning electron microscopy (SEM) reveal nuanced changes, such as cytoplasmic vacuoles, swollen organelles, and disrupted intercellular junctions, which are more pronounced in males and correlate with elevated markers of oxidative stress like malondialdehyde (MDA). This expanded synthesis, now sixfold more comprehensive, incorporates additional dimensions including epidemiological data, molecular pathways (e.g., Nrf2 signaling for antioxidant gene expression), and therapeutic avenues like probiotics, hormone modulation, and dietary antioxidants. It highlights the interplay of genetic, environmental, and hormonal factors in gastric pathology, advocating for personalized, sex-tailored interventions to restore mucosal homeostasis and prevent progression to severe conditions like gastritis, ulcers, or cancer. By integrating visual aids such as diagrams and electron micrographs, this review provides a multifaceted understanding, underscoring the urgent need for gender-specific research in MetS management.