Liaw SJ, Chen JC, Ng CJ, Chiu DF, Chen MF, Chen HM.
Department of Emergency Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
BACKGROUND AND PURPOSE: Lipopolysaccharide (LPSi) induces hemodynamic changes and microcirculatory derangement in various organs. Melatonini may exert a beneficial effect on gastric tissue in LPS-induced gastropathy. However, the role of nitric oxide (NO) has not been clarified. MATERIALS AND 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.
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CAPii for Cpnii 11/04. Dxi: 25yrs CFSii & FMSii. Currently: 250 aithromycin mwf, doxycycline 100mg BIDii, Tinii 1000mg/day pulses; Vit D2000 units, T4 & T3, 12mg Iodoral