title: Protection against acute paraquat toxicity by ambroxol.
abstract: 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.
authors.affiliation: Laboratorio di Enzimologia, Istituto di Ricerche Farmacologiche "Mario Negri", Via Eritrea62, 20157, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Perin
authors.forename: M
authors.initials: M
authors.lastname: Donnini
authors.forename: L
authors.initials: L
authors.lastname: Diomede
authors.forename: M
authors.initials: M
authors.lastname: Romano
authors.forename: M T
authors.initials: MT
authors.lastname: Tacconi
authors.forename: M
authors.initials: M
authors.lastname: Luisetti
authors.forename: M
authors.initials: M
authors.lastname: Salmona