Molecular Mechanisms of Melatonin Protection from Gastric Mucosal Apoptotic Injury in Experimental Burns

Abstract

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.

Melatonin for prevention of placental malperfusion and fetal compromise associated with intrauterine inflammation‐induced oxidative stress in a mouse model

“…This finding is supported by our results showing a reduction in placental gene expression and proteins of pro-inflammatory mediators and oxidative stress markers, 4-HNE. 39 We also observed that A previous study has demonstrated an association between inflammatory markers and thrombotic pathology. 40 Elevated levels of C-reactive protein have been associated with an increased risk of venous thromboembolism, 41 and increased levels of certain pro-inflammatory substances, such as IL-6, have been linked with venous thrombosis.…”

“…Our study is the first to examine the beneficial effect of antenatal maternally administered melatonin on fetoplacental hemodynamic changes and fetal neuroinflammation caused from IUI‐induced oxidative stress. This finding is supported by our results showing a reduction in placental gene expression and proteins of pro‐inflammatory mediators and oxidative stress markers, 4‐HNE . We also observed that melatonin pretreatment induced an increase in anti‐inflammatory precursor, SIRT1, Nrf2, and HO‐1, suggesting a beneficial neuroprotective effect against an inflammatory insult.…”

Edaravone reduces oxidative stress and intestinal cell apoptosis after burn through up-regulating miR-320 expression

“…The occurrence of apoptosis is regulated by apoptosis-related genes, including Bcl-2, Bax, caspase family and Fas membrane proteins, etc. (Hristova et al, 2018) . Bcl-2 is an anti-apoptosis protein and has the function of inhibiting the release of apoptosis factors such as cytochrome C (Negroni et al, 2015) .…”

The implication of the crosstalk of Nrf2 with NOXs, and HMGB1 in ethanol-induced gastric ulcer: Potential protective effect is afforded by Raspberry Ketone

“…The manufacturer's instructions were accurately followed. The ratio of Bax to Bcl-2 was calculated using the formula [29]: …”