Effects of melatonin in an experimental model of ventilator-induced lung injury.
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 cmH(2)O, positive end-expiratory pressure (PEEP) 2 cmH(2)O], and high-pressure ventilation (peak inspiratory pressure 25 cmH(2)O, PEEP 0 cmH(2)O). 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-1beta, IL-6, TNF-alpha, 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-alpha, 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-alpha, IL-1beta, 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.
Pedreira
Paula R
PR
Intensive Care Unit, Hospital Universitario Central de Asturias, Celestino Villamil s/n, Oviedo, Spain.
García-Prieto
Emilio
E
Parra
Diego
D
Astudillo
Aurora
A
Diaz
Elena
E
Taboada
Francisco
F
Albaiceta
Guillermo M
GM
D000818:Animals; D004195:Disease Models, Animal; D004487:Edema / Q000150:complications; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007249:Inflammation; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D055397:Ventilator-Induced Lung Injury / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology
D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D018093:Gelatinases; D008550:Melatonin