The effect and mechanism of action of carbocysteine on airway bacterial load in rats chronically exposed to cigarette smoke.

Carbocysteine (S-carboxymethylcysteine) is a mucoactive drug with in vitro free radical scavenging and anti-inflammatory properties. Several clinical trials have indicated that carbocysteine reduces exacerbation rates in COPD. In the present study, the effect of carbocysteine on the airway load of Haemophilus influenzae was assessed in rats chronically exposed to cigarette smoke (CS). In addition, the effects of carbocysteine on airway mucus hypersecretion and mucociliary clearance (MCC) associated with the adherence and clearance of H. influenzae were investigated. Wistar rats were randomly divided into control, carbocysteine vehicle, CS exposure and carbocysteine treatment groups. After 12 weeks, rats were selected for quantitative inoculation of H. influenzae. BAL fluid and lungs were collected aseptically after 3 h for quantitative culture of H. influenzae. MCC was measured by quantifying the clearance of (99m)Tc-Sc. Goblet cell metaplasia and the presence of mucoid matter were evaluated by Alcian blue/periodic acid-Schiff staining. Mucin 5AC (Muc5AC) expression was detected by western blotting and real-time reverse transcription-PCR. Exposure to CS increased airway H. influenzae load, aggravated mucus hypersecretion and delayed MCC. Treatment with carbocysteine decreased airway H. influenzae load, and attenuated airway mucus hypersecretion, with improved MCC associated with adherence and clearance of H. influenzae. These results suggest that carbocysteine may be beneficial in patients with COPD by increasing the clearance of bacteria and decreasing bacterial load.