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Melatonin, a major hormone of pineal gland, was recently show to attenuate acute gastric lesions induced by strong irritants because of the scavenging of free radicals. The effect of melatonin on burninduced gastric mucosal injury due to the skin burn is unclear. PURPOSE: This study investigated heme oxygenase-1 and markers linked with oxidative stress in gastric mucosa and the effect of melatonin in burn rat model. METHODS: Melatonin was applied immediately and 12 hours after 30% of total body surface area burns. Using light immunohistochemistry the expression of gastric mucosal inducible nitric oxide synthase (iNOS) and heme oxygenase (HO-1) was found out. Malondialdehyde (MDA) as a marker of oxidative injury was determined in gastric mucosa by the thiobarbituric acid method. RESULTS: Gastric MDA and iNOS levels were increased significantly after severe burn (p<0.05, p<0.0001, respectively). The increased HO-1 expression in the burned group was found out (p<0.05). Melatonin restricted the increased MDA (p<0.05) and iNOS (p<0.05) levels, and augmented the increase in HO-1 expression in gastric mucosa (p<0.05). In conclusion, melatonin ameliorates gastric mucosal injury via induction of antioxidant enzyme HO-1 and inhibition of oxidative stress beyond local burn skin injury.

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 (0.94–1.47)), decreased anti-apoptotic Bcl-2 protein (1.16 (1.06–1.23), p < 0.001) in epithelial cells, and elevated Bax/Bcl-2 ratios (p < 0.05). Tissue 4-HNE and Nrf2 levels were increased following severe burns (1.55 (0.98–1.61) and 1.16 (1.01–1.25), p < 0.05, respectively). Melatonin significantly decreased 4-HNE (0.87 (0.74–0.96), p < 0.01) and upregulated Nrf2 (1.55 (1.52–1.65), p < 0.001) levels. It also augmented Bax (1.68 (1.5–1.8), p < 0.001) and Bcl-2 expressions (1.96 (1.89–2.01), p < 0.0001), but reduced Bax/Bcl-2 ratios (p < 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.