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


METHODS
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.


RESULTS
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.


CONCLUSIONS
These results suggest that carbocysteine may be beneficial in patients with COPD by increasing the clearance of bacteria and decreasing bacterial load.
Sun
Li
L
Institute of Respiratory Diseases, First Affiliated Hospital of China Medical University, Shenyang, China.
Tang
Lifeng
L
Xu
Yan
Y
Wang
Shouqin
S
Li
Yaming
Y
Kang
Jian
J
D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects*; D058491:Bacterial Load / Q000187:drug effects; D002233:Carbocysteine / Q000008:administration & dosage*; D005100:Expectorants / Q000008:administration & dosage*; D020397:Goblet Cells / Q000187:drug effects; D006192:Haemophilus Infections / Q000188:drug therapy*; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000302:isolation & purification; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects; D009093:Mucus / Q000187:drug effects / Q000382:microbiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000382:microbiology*; D051381:Rats; D017208:Rats, Wistar; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects; D014026:Nicotiana / Q000009:adverse effects*; D016896:Treatment Outcome
D005100:Expectorants; D012906:Smoke; D002233:Carbocysteine