Melatonin plays a protective role in postburn rodent gut pathophysiology

Area of Science:

• Biomedical Science
• Physiology
• Pharmacology

Background:

• Major thermal injury causes significant gut pathophysiological changes, including inflammation.
• Melatonin, a hormone with antioxidant and anti-inflammatory properties, is a potential therapeutic agent for postburn complications.

Purpose of the Study:

• To investigate the role of endogenous and exogenous melatonin in postburn gut inflammation.
• To determine if the gut serves as both a source and a target for melatonin.
• To evaluate melatonin's potential as a therapeutic agent for postburn gut inflammation.

Main Methods:

• Rats with third-degree burns (30% TBSA) were used to model postburn gut inflammation.
• Melatonin levels in systemic and mesenteric circulation were measured using ELISA.
• Expression of melatonin-synthesizing enzymes (AA-NAT, HIOMT) in the jejunum and ileum was assessed using rtPCR.
• Effects of exogenous melatonin administration on gut inflammation markers (neutrophil infiltration, nitrotyrosine) were evaluated using immunohistochemistry.

Main Results:

• Mesenteric melatonin levels were higher than systemic levels and increased postburn.
• Expression of AA-NAT and HIOMT in the jejunum and ileum increased postburn.
• Exogenous melatonin supplementation (8 micromole/kg) significantly suppressed neutrophil infiltration and nitrotyrosine levels in the gut mucosa.
• Higher dose (32 micromole/kg) of exogenous melatonin suppressed AA-NAT mRNA expression, suggesting negative feedback.

Conclusions:

• The gut is a source of melatonin, with increased endogenous production following thermal injury.
• While endogenous melatonin increases postburn, it may not be sufficient to control inflammation.
• Exogenous melatonin administration demonstrates significant anti-inflammatory effects, supporting its therapeutic potential in managing postburn gut inflammation.