Melatonin is the principal secretory product of the pineal gland and its role as an immuno-modulator is well established. Recent evidence shows that
melatonin is a scavenger of oxyradicals and
peroxynitrite and exerts protective effects in
septic shock,
hemorrhagic shock and
inflammation. The aim of this study was to investigate the effect of
melatonin on the
lung injury caused by
bleomycin (BLM) administration. Mice subjected to intratracheal administration of BLM developed significant
lung injury characterized by a marked neutrophil infiltration [assessed by
myeloperoxidase (MPO) activity] and by tissue
edema. In addition, an increase of immunoreactivity to
nitrotyrosine,
poly-ADP-ribose (PAR) was also observed in the lung of BLM-treated mice. Also,
lung injury induced by BLM administration was correlated with a significant loss of
body weight and with a significant mortality. Administration of
melatonin (10 mg/kg i.p.) daily significantly reduced the (i) loss of
body weight, (ii) mortality rate, (iii) infiltration of the lung with polymorphonuclear neutrophils (MPO activity), (iv)
edema formation and (v) histological evidence of
lung injury. Administration of
melatonin also markedly reduced the
nitrotyrosine and PAR formation. Taken together, our results demonstrate that treatment with
melatonin significantly reduces
lung injury induced by BLM in the mice.