Protection against acute paraquat toxicity by ambroxol

One of the earliest biochemical effects induced by the herbicide paraquat (PQ) is damage to type II pneumocytes with consequent depletion of surfactant (Skillrud and Martin, 1984). We made a series of studies on the possible protective effect of drug ambroxol, which induces surfactant synthesis from alveolar type II cells (Post et al. 1983). The cell line A-549, exposedin vitro to PQ concentrations ranging from 0.5×10(-4) to 2×10(-3) M, showed a significant dose-dependent loss of viability. Ambroxol (10 mg/ml) pretreated cells were more resistant to PQ, their viability starting to decrease from a PQ concentration of 0.8×10(-3) M. Membrane microviscosity was measured on the same cells. Cells treated with PQ alone showed a reduction of membrane microviscosity which was significantly counteracted by ambroxol pretreatment. The curves for membrane microviscosity of PQ and ambroxol-plus-PQ-treated cells overlapped those for cell viability, indicating that the stimulation of surfactant synthesisin vitro may be a prerequisite for counteracting some of the precocious effects of PQ. Partial protection from PQ- induced mortality was also obtainedin vivo.