Effect of ambroxol on oxygen radical production and generation by bronchoalveolar lavage cells in young and aged guinea pigs.

We examined the effect of ambroxol and age on oxygen radical production and generation with stimulation of phorbol-myristate acetate (PMA) by bronchoalveolar lavage (BAL) cells. Lung free cells including pulmonary alveolar macrophages were harvested from young (4-month-old) and aged (28-month-old) male guinea pigs using BAL. The oxygen radicals produced by BAL cells with or without stimulation of PMA were measured by the lucigenin-dependent chemiluminescence method using a photon counter. Oxygen radical production and generation by BAL cells were not different between young and aged guinea pigs. However, the oxygen radical generation after stimulation with PMA was greater than the oxygen radical spontaneous production both in young and aged animals. Ambroxol solution given into culture media containing BAL cells inhibited oxygen radical production and generation by BAL cells harvested from both young and aged guinea pigs in a concentration-dependent manner. Approximately 16-20 microM of ambroxol inhibited 50% of the production of oxygen radicals in vitro by BAL cells in young and aged guinea pigs, whereas a slightly greater amount of ambroxol was necessary to inhibit 50% of the PMA-induced oxygen radical generation in vitro by BAL cells in guinea pigs. These results indicate that ambroxol inhibits oxygen radicals produced by BAL cells from young and aged guinea pigs, and they suggest that ambroxol may be a possible therapeutic modality for ameliorating oxidant associated pulmonary disorders in young and aged patients.