Depressant effect of ambroxol on stimulated functional responses and cell death in rat alveolar macrophages exposed to silica in vitro.
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.
Kim
Young Ki
YK
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea.
Jang
Yoon Young
YY
Han
Eun Sook
ES
Lee
Chung Soo
CS
D000135:Acid Phosphatase / Q000378:metabolism; D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology; D005100:Expectorants / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009113:Muramidase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst / Q000187:drug effects; D012822:Silicon Dioxide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D013481:Superoxides / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D005100:Expectorants; D009573:Nitrites; D016877:Oxidants; D013778:Tetrazolium Salts; D013844:Thiazoles; D013481:Superoxides; D000551:Ambroxol; D012822:Silicon Dioxide; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D000135:Acid Phosphatase; D009113:Muramidase; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C022616:thiazolyl blue; D002118:Calcium