TY - JOUR T1 - Depressant Effect of Ambroxol on Stimulated Functional Responses and Cell Death in Rat Alveolar Macrophages Exposed to Silica in Vitro JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 629 LP - 637 DO - 10.1124/jpet.300.2.629 VL - 300 IS - 2 AU - Young Ki Kim AU - Yoon Young Jang AU - Eun Sook Han AU - Chung Soo Lee Y1 - 2002/02/01 UR - http://jpet.aspetjournals.org/content/300/2/629.abstract N2 - The present study examined the effect of ambroxol on free radical production, granule enzyme release, and cell death in silica-activated rat alveolar macrophages. The action of ambroxol was assayed by measuring changes in the activities of protein kinase C (PKC) and tyrosine kinase (PTK) and in the intracellular calcium level. Ambroxol attenuated the production of superoxide, hydrogen peroxide, and nitric oxide and the release of acid phosphatase and lysozyme in macrophages activated by silica. Staurosporine, genistein, EGTA, and trifluoperazine inhibited the silica-induced free radical production and granule enzyme release. Silica induced the increase in PKC and PTK activities and the elevation of intracellular calcium level in macrophages, which was decreased by ambroxol. Silica induced a cell death and increased the caspase-3 activity in macrophages in a concentration-dependent manner. Ambroxol decreased the silica-induced cell viability loss in macrophages. The results show that ambroxol decreases the stimulated responses and cell death in rat alveolar macrophages exposed to silica, which may be accomplished by inhibition of activation processes, protein kinases, and calcium transport. The inhibitory effect of ambroxol on silica-induced cell death appears to provide the protective effect on pulmonary tissues against the toxic action of silica. The American Society for Pharmacology and Experimental Therapeutics ER -