title: Therapeutic effects of hyaluronan on smoke-induced elastic fiber injury: does delayed treatment affect efficacy?
abstract: Aerosolized hyaluronan (HA) has been previously shown to prevent cigarette smoke-induced airspace enlargement and elastic fiber injury in mice when given concurrently with smoke. In the present study, a more stringent test of the therapeutic potential of HA was performed by delaying treatment with this agent for 1 month. After treatment with cigarette smoke for 3 h per day for 5 days per week for 1 month, mice (DBA/2J) began receiving aerosolized HA (0.1%) for 1 h prior to smoke exposure (controls were given aerosolized water). The results indicate that much of the damage to the lung elastic fibers occurred within the first several months of smoke exposure, as measured by levels of desmosine and isodesmosine (DID) in bronchoalveolar lavage fluid (BALF). In contrast to previously published studies, where concurrent administration of aerosolized HA significantly reduced BALF DID levels within 3 months of smoke exposure, the same effect was not seen until 6 months when HA treatment was delayed. However, despite the prolonged breakdown of elastic fibers in the current study, a significant reduction in airspace enlargement was observed after only 2 months of HA treatment. These findings provide further support for testing this agent in patients with pre-existing chronic obstructive pulmonary disease.
authors.affiliation: St Luke's Roosevelt Hospital Center, New York, NY, USA. jocantor@pol.net
authors.forename: Jerome O
authors.initials: JO
authors.lastname: Cantor
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Cerreta
authors.forename: Marcos
authors.initials: M
authors.lastname: Ochoa
authors.forename: Shuren
authors.initials: S
authors.lastname: Ma
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Turino
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003895:Desmosine / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004547:Elastic Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D007524:Isodesmosine / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011656:Pulmonary Emphysema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D000336:Aerosols; D003895:Desmosine; D006820:Hyaluronic Acid; D007524:Isodesmosine