Antioxidant activity of carbocysteine lysine salt monohydrate

Background. Reactive oxygen radicals are involved in many respiratory disea ses, including chronic obstructive pulmonary disease (COPD). Carbocysteine lysine salt monohydrate (CLS) is a mucoactive drug effective in the treatme nt of bronchopulmonary diseases characterized by mucus alterations, includi ng COPD. In the present study, the antioxidant activity of CLS was studied in vitro in three different oxygen radical producing systems, i.e. bronchoa lveolar lavages (BAL) from patients affected by COPD, ultrasound treated hu man serum and cultured human lung endothelial cells challenged with elastas e. Methods. BAL, exposed or not to different concentrations of CLS (1.5-30 mM) , was assayed for free radical content by fluorometric analysis of DNA unwi nding (FADU) or by cytochrome c reduction kinetics. Human serum was treated with ultrasound in the presence or absence of CLS (1.5, 2.5 mM) or N-acety l cysteine (NAC; 4,5 mM) and assayed for free radical content by FADU. Huma n endothelial cells cultured in vitro from pulmonary artery were incubated with elastase (0.3 I.U./mL), in the presence or absence of glutathione (GSH ; 0.65 mM) or CLS (0.16 mM). The supernatant was tested for cytochrome c re duction kinetics whereas cell homogenates were assessed for xanthine oxidas e (XO) content by SDS-PAGE. Results. Results showed that CLS is more effective as an in vitro scavenger in comparison to GSH and NAC. CLS reduced the damage of DNA from healthy d onors exposed to COPD-BAL and was able to quench clastogenic activity induc ed in human serum by exposure to ultrasound at concentrations as low as 2.5 mM. NAC protect DNA from radical damage, starting from 5 mM. In human lung endothelial cells cultured in presence of elastase, CLS (0.16 mM) decrease d xanthine oxidase activity. Conclusions. These results suggest that CLS could act by interfering with t he conversion of xanthine dehydrogenase into superoxide-producing xanthine oxidase. The antioxidant activity of CLS could contribute to its therapeuti c activity by reducing radical damage to different lung structures.