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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/L820    most recent 90211.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Pedreira, P. R. Articles by Albaiceta, G. M. Search for Related Content PubMed PubMed Citation Articles by Pedreira, P. R. Articles by Albaiceta, G. M.

Effects of melatonin in an experimental model of ventilator-induced lung injury

¹Intensive Care Unit, Hospital Universitario Central de Asturias; and ²Departamento de Cirugía y Especialidades Médico-Quirurgicas, ³Departamento de Biología Funcional, and ⁴Departamento de Medicina, Universidad de Oviedo, Oviedo, Spain

Submitted 26 February 2008 ; accepted in final form 16 September 2008

Melatonin is a free radical scavenger and a broad-spectrum antioxidant and has well-documented immunomodulatory effects. We studied the effects of this hormone on lung damage, oxidative stress, and inflammation in a model of ventilator-induced lung injury (VILI), using 8- to 12-wk-old Swiss mice (n = 48). Animals were randomized into three experimental groups: control (not ventilated); low-pressure ventilation [peak inspiratory pressure 15 cmH₂O, positive end-expiratory pressure (PEEP) 2 cmH₂O], and high-pressure ventilation (peak inspiratory pressure 25 cmH₂O, PEEP 0 cmH₂O). Each group was divided into two subgroups: eight animals were treated with melatonin (10 mg/kg ip, 30 min before the onset of ventilation) and the remaining eight with vehicle. After 2 h of ventilation, lung injury was evaluated by gas exchange, wet-to-dry weight ratio, and histological analysis. Levels of malondialdehyde, glutathione peroxidase, interleukins IL-1β, IL-6, TNF-, and IL-10, and matrix metalloproteinases 2 and 9 in lung tissue were measured as indicators of oxidation status, pro-/anti-inflammatory cytokines, and matrix turnover, respectively. Ventilation with high pressures induced severe lung damage and release of TNF-, IL-6, and matrix metalloproteinase-9. Treatment with melatonin improved oxygenation and decreased histological lung injury but significantly increased oxidative stress quantified by malondialdehyde levels. There were no differences in TNF-, IL-1β, IL-6, or matrix metalloproteinases caused by melatonin treatment, but IL-10 levels were significantly higher in treated animals. These results suggest that melatonin decreases VILI by increasing the anti-inflammatory response despite an unexpected increase in oxidative stress.

mechanical ventilation; oxidative stress