Author Affiliations: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China (Pan L, Fu JH, Xue XD, Xu W, Wei B); Department of Pediatrics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China (Zhou P)

Corresponding Author: Xin-Dong Xue, MD, Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China (Tel: +86-24-83955509; Fax: +86-024-83955509; Email: xdxue@163.com)

doi:10.1007/s12519-009-0041-2

Background: Oxidative stress plays an important role in the pathogenesis of bronchopulmonary dysplasia (BPD). Melatonin (MT) has direct and indirect free radical detoxifying activity. The present study was to investigate whether treatment with MT would attenuate hyperoxia-induced lung injury and the effect of MT on imbalance of oxidants/antioxidants in the lung of neonatal rats.

Methods: BPD was induced by exposure to hyperoxia in neonatal rats (n=90). The rats were divided randomly into three groups (n=30 each): air-exposed control group, hyperoxia-exposed group, and hyperoxia-exposed MT-treated group. Lung specimens were obtained respectively on day 3, day 7, and day 14 after exposure (n=10 each). Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and levels of myeloperoxidase (MPO), nitrite/nitrate, and malondialdehyde (MDA) were assayed. Histopathologic changes were observed in the tissues stained with hematoxylin and eosin and Masson's trichrome stain.

Results: Increased levels of MPO, nitrite/nitrate, and MDA in the hyperoxia-exposed rats were significantly reduced by MT (P<0.05). Activities of GSH-Px, SOD, and CAT which did not change after exposure to hyperoxia were increased by MT (P<0.05). Furthermore, BPD associated histopathological alterations such as reduced total number of alveoli and interstitial fibrosis were obviously abated in the MT-treated group.

Conclusions: MT can reverse oxidants/antioxidants imbalance in damaged lung tissue and thus exert a beneficial effect on hyperoxia-induced lung disease in neonatal rats. With regard to humans, there may be a protective effect of MT on BPD.

Key words: antioxidants; bronchopulmonary dysplasia; free radicals; lung damage；melatonin