title: Effect of Myrtol standardized on mucus hypersecretion and clearance of Pseudomonas aeruginosa in a rat model of chronic obstructive pulmonary disease.
abstract: This study aimed to investigate the effect of Myrtol standardized (GeloMyrtol forte) in the treatment of chronic obstructive pulmonary disease (COPD) in an animal model. A total of 93 experimental rats were randomly divided into 6 groups: control (n = 6), exposure to cigarette smoke (CS, n = 6), CS plus Myrtol standardized treatment (CS + M, n = 6), Pseudomonas aeruginosa (PA) infection (PA, n = 25), CS + PA (n = 25), and CS + PA + M (n = 25). For all 62 CS rats, they were exposed to cigarette smoke for a period of 12 weeks. During this time period the 31 CS + M rats (CS + M; CS + PA + M) received 300 mg/kg/day Myrtol standardized intragastrically always 30 min prior to smoke exposure. For CS + PA and CS + PA + M rats, intratracheal PA inoculation was performed after the 12 weeks of smoke exposure. All intratracheal PA inoculations were followed by a post-infection examination at 6, 12, 24, 48 and 72 h in each 5 rats. All study animals were euthanized and their lungs were excised; the left lung was homogenized for determination of bacterial load and measurements of TNF-alpha and IL-6, the right lungs were preserved for histo- and immunohistochemical examinations (e. g. MUC5AC). The lungs from CS rats were pathologically similar to those of COPD patients with the characteristics of goblet cell metaplasia and MUC5AC hypersecretion. CS animals had a significantly greater number of MUC5AC positive cells in the bronchial epithelial cells, and significantly increased expression levels of TNF-alpha and IL-6 after PA infection. However, the administration of Myrtol standardized significantly (p = 0.002) attenuated MUC5AC hypersecretion, measured as integrity optical density (IOD), in CS + M rats (45.98 +/- 6.25) as compared to CS alone (65.55 +/- 11.18) rats. The same applies at different time points between CS + PA rats (65.15 +/- 11.94, 75.88 +/- 7.42, 81.2 +/- 6.49, 75.14 +/- 6.85 and 67.32 +/- 10.61, respectively) and CS + PA + M rats (47.08 +/- 4.78, 54.22 +/- 6.59, 65.4 +/- 6.12, 59.98 +/- 4.96 and 48.43 +/- 7.29, respectively). Similar effects were found in the production of IL-6 and TNF-alpha in the CS + PA + M lungs. Similarly the bacterial load of 10,980 +/- 4,253 CFU in CS + PA + M was significantly lower compared to 42,400 +/- 3,296 CFU in CS + PA lungs after 72 h PA infection. In conclusion, this experimental study demonstrates a significant therapeutic effect of Myrtol standardized in treating common pathological conditions, such as airway mucus hypersecretion and defect of mucociliary functions in COPD.
authors.affiliation: Institute of Respiratory Disease, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Cao
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhang
authors.forename: Shengli
authors.initials: S
authors.lastname: Wang
authors.forename: Zhenshan
authors.initials: Z
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
mesh_terms: D000818:Animals; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004338:Drug Combinations; D005100:Expectorants / Q000627:therapeutic use*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D039821:Monoterpenes / Q000627:therapeutic use*; D055271:Mucin 5AC / Q000096:biosynthesis / Q000235:genetics; D009093:Mucus / Q000187:drug effects / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001993:Bronchodilator Agents; D016207:Cytokines; D004338:Drug Combinations; D005100:Expectorants; D015850:Interleukin-6; D039821:Monoterpenes; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D014028:Tobacco Smoke Pollution; D014409:Tumor Necrosis Factor-alpha; C055632:myrtol