Ambroxol inhibits peroxynitrite-induced damage of alpha1-antiproteinase and free radical production in activated phagocytic cells.
The present study examined the effect of ambroxol on toxic action of peroxynitrite and the respiratory burst in activated phagocytic cells. Ambroxol decreased the inactivation or destruction of alpha1-antiproteinase induced by peroxynitrite (ONOO-) or hypochlorous acid (HOCl), which was similar to penicillamine and glutathione and was greater than diclofenac sodium and naproxen sodium. Ambroxol significantly decreased ONOO--mediated tyrosine nitration and iron plus EDTA-mediated degradation of 2-deoxy-D-ribose. Ambroxol significantly attenuated the production of superoxide, hydrogen peroxide, HOCl, and nitric oxide in fMLP- or IL-1-activated phagocytic cells, while the inhibitory effects of antiinflammatory and thiol compounds were only observed in HOCl production. Ambroxol and antiinflammatory drugs did not show a cytotoxic effect on macrophages. The results suggest that ambroxol protects tissue components against oxidative damage by an action different from antiinflammatory drugs. Ambroxol may interfere with oxidative damage of alpha1-antiproteinase through a scavenging action on ONOO- and HOCl and inhibition of the respiratory burst of phagocytic cells.
Lee
Chung Soo
CS
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea. leecs@cau.ac.kr
Jang
Yoon Young
YY
Song
Joon Sup
JS
Song
Jin Ho
JH
Han
Eun Sook
ES
D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010586:Phagocytes / Q000187:drug effects* / Q000201:enzymology; D016897:Respiratory Burst / Q000187:drug effects; D000515:alpha 1-Antitrypsin / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000515:alpha 1-Antitrypsin; D030421:Peroxynitrous Acid; D000551:Ambroxol; D006997:Hypochlorous Acid