Melatonin ameliorates gastric mucosal damage induced by ethanol and heat stress: A comparative biochemical and histomorphometric study.

Gastric mucosal injury is a common clinical problem caused by different stressors that disrupt the gastric mucosal barrier through distinct mechanisms. This study aimed to compare acute gastric mucosal injury induced by ethanol and heat stress and to assess the therapeutic efficacy of melatonin relative to spontaneous recovery. Acute gastric injury was induced in adult male Sprague-Dawley rats using ethanol administration or repeated heat stress exposure. Animals were then subjected to a 7-day recovery period with or without melatonin treatment. Gastric tissues were evaluated using biochemical assays of oxidative, nitrosative, and inflammatory markers, as well as histological and morphometric analyses. Ethanol induced severe mucosal injury characterized by extensive epithelial disruption, marked inflammation, oxidative and nitrosative stress, mucosal thinning, and significant fibrotic changes. Heat stress produced milder, superficial injury with partial preservation of glandular architecture and greater intrinsic recovery capacity. Spontaneous recovery after ethanol exposure was incomplete, as evidenced by persistent histological damage, elevated malondialdehyde (MDA), nitric oxide (NO), and tumor necrosis factor-α levels (TNF-α), and impaired antioxidant defenses. In contrast, recovery following heat stress showed better restoration of antioxidant capacity and reduced inflammation. Melatonin treatment significantly ameliorated gastric injury in both models, outperforming spontaneous recovery. Melatonin reduced oxidative and inflammatory markers, enhanced antioxidant defenses, preserved mucosal thickness, limited collagen deposition, and improved mucin production, with more pronounced effects in the heat stress model. Overall, these findings demonstrate that melatonin effectively accelerates gastric mucosal repair by affecting oxidative, inflammatory, and fibrotic pathways, with therapeutic efficacy dependent on the nature and depth of the initial injury.