{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:50:10Z","timestamp":1784721010375,"version":"3.55.0"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T00:00:00Z","timestamp":1521849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Melatonin, a basic secretory pineal gland product, is a nontoxic, multifunctional molecule. It has antioxidant and anti-apoptotic activities and protects tissues from injury. The objective of the present study was to determine the molecular mechanism of melatonin anti-apoptotic effect on gastric injury in a rat burn model. We hypothesized that melatonin gastric protection may be related to the activation of transcription erythroid 2-related factor 2 (Nrf2). Using a 30% total body surface area (TBSA) rat burn model, melatonin (10 mg\/kg, i.p.) was injected immediately and 12 h after thermal skin injury. Via light immunohistochemistry, we determined the tissue level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipid peroxidation, Bcl-2 and Bax as apoptosis-related proteins, and Nrf2. Results are presented as medians (interquartile range (IQR)). Thermal trauma in burned animals, compared with the controls, increased the expression of pro-apoptotic Bax protein (1.37 (0.94\u20131.47)), decreased anti-apoptotic Bcl-2 protein (1.16 (1.06\u20131.23), p &lt; 0.001) in epithelial cells, and elevated Bax\/Bcl-2 ratios (p &lt; 0.05). Tissue 4-HNE and Nrf2 levels were increased following severe burns (1.55 (0.98\u20131.61) and 1.16 (1.01\u20131.25), p &lt; 0.05, respectively). Melatonin significantly decreased 4-HNE (0.87 (0.74\u20130.96), p &lt; 0.01) and upregulated Nrf2 (1.55 (1.52\u20131.65), p &lt; 0.001) levels. It also augmented Bax (1.68 (1.5\u20131.8), p &lt; 0.001) and Bcl-2 expressions (1.96 (1.89\u20132.01), p &lt; 0.0001), but reduced Bax\/Bcl-2 ratios (p &lt; 0.05). Our results suggest that experimental thermal trauma induces oxidative gastric mucosal injury. Melatonin manifests a gastroprotective effect through Nrf2 activation, lipid peroxidation attenuation, and Bax\/Bcl-2 ratio modification as well.<\/jats:p>","DOI":"10.3390\/molecules23040749","type":"journal-article","created":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T03:43:29Z","timestamp":1522035809000},"page":"749","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular Mechanisms of Melatonin Protection from Gastric Mucosal Apoptotic Injury in Experimental Burns"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8466-686X","authenticated-orcid":false,"given":"Minka","family":"Hristova","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, Medical University of Varna, Varna 9002, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Tzaneva","sequence":"additional","affiliation":[{"name":"Department of Preclinical and Clinical Sciences, Medical University of Varna, Varna 9002, Bulgaria"},{"name":"Department of General and Clinical Pathology, Forensic Science and Deontology, Medical University of Varna, Varna 9010, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5611-4803","authenticated-orcid":false,"given":"Ganka","family":"Bekyarova","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Medical University of Varna, Varna 9002, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariya","family":"Chivchibashi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, Medical University of Varna, Varna 9002, Bulgaria"},{"name":"Department of General and Clinical Pathology, Forensic Science and Deontology, Medical University of Varna, Varna 9010, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-4824","authenticated-orcid":false,"given":"Nadezhda","family":"Stefanova","sequence":"additional","affiliation":[{"name":"Department of General and Clinical Pathology, Forensic Science and Deontology, Medical University of Varna, Varna 9010, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9692-6227","authenticated-orcid":false,"given":"Yoana","family":"Kiselova-Kaneva","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University of Varna; Varna 9002, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.2119\/molmed.2009.00005","article-title":"The hepatic response to thermal injury: Is the liver important for postburn outcomes?","volume":"15","author":"Jeschke","year":"2009","journal-title":"Mol. 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