Beneficial role of melatonin on microcirculation in endotoxin-induced gastropathy in rats: possible implication in nitrogen oxide reduction.
OBJECTIVE
Lipopolysaccharide (LPS) induces hemodynamic changes and microcirculatory derangement in various organs. Melatonin may exert a beneficial effect on gastric tissue in LPS-induced gastropathy. However, the role of nitric oxide (NO) has not been clarified.


METHODS
Adult male Sprague-Dawley rats were divided into three groups: control, n = 9; LPS (intraperitoneal LPS, 50 mg/kg), n = 9; and LPS + M (LPS, 50 mg/kg; intragastric melatonin 20 mg/kg), n = 9. Mean arterial blood pressure (MAP) was monitored throughout the experiment (8 h). In vivo microscopy was used to investigate gastric microcirculation, including flow velocity and leukocyte adhesion. Tissue malondialdehyde (MDA) and gastric aspirate parameters (protein content, glucose content, volume) were determined as the gastric damage index at the end of the experiment. Microdialysis was used to measure the sum of nitrite and nitrate concentrations.


RESULTS
Compared with LPS alone, LPS with melatonin significantly improved gastric microcirculation but not systemic hemodynamics. LPS-induced gastropathy was quantified according to the increased adherent leukocyte count, decreased flow velocity in postcapillary venules, and increased tissue MDA production. Luminal glucose and protein content, the gastric mucosa injury index, were significantly increased. Intragastric melatonin improved microcirculatory and mucosa injury parameters. These effects of melatonin are directly associated with the tissue levels of NO products, which are increased with LPS only and much decreased with LPS and melatonin.


CONCLUSIONS
This study demonstrated that melatonin contributes to the protective effects in LPS-induced gastropathy through a mechanism associated with regional production of NO.
Liaw
Shiumn-Jen
SJ
Department of Emergency Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
Chen
Jih-Chang
JC
Ng
Chip-Jin
CJ
Chiu
De-Fa
DF
Chen
Miin-Fu
MF
Chen
Han-Ming
HM
D000818:Animals; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects*; D008070:Lipopolysaccharides; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008833:Microcirculation; D017551:Microdialysis; D009102:Multiple Organ Failure / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D008550:Melatonin