Effects of dosage and timing of administration of a peptide boronic acid inhibitor on lung mechanics and morphometrics in elastase-induced emphysema in hamsters.
The peptide boronic acid, MeOSuc-Ala-Ala-Pro-boroVal-pinacol (AAPbV), is an effective inhibitor of both pancreatic and leukocyte elastase. Initial work showed that AAPbV diminishes the effect of emphysema induced by pancreatic elastase. This initial work has been expanded to show that AAPbV provides a high degree of protection against elastase-induced increases in lung volume and mean linear intercept when given intratracheally at 200 mg/kg either 15 min before, simultaneous with, or 15 min after instilling elastase. Intraperitoneal administration, although less effective, is dose dependent and dependent on the time of treatment. We conclude that a reversible protease inhibitor can be used to prevent aberrant proteolysis in vivo.
D000818:Animals; D001696:Biomechanical Phenomena; D001897:Boronic Acids / Q000008:administration & dosage* / Q000627:therapeutic use*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D008168:Lung / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008647:Mesocricetus; D009842:Oligopeptides / Q000008:administration & dosage* / Q000627:therapeutic use; D010196:Pancreatic Elastase; D010455:Peptides / Q000627:therapeutic use*; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control
D001897:Boronic Acids; D009842:Oligopeptides; D010455:Peptides; C048437:methyl-O-succinyl-alanyl-alanyl-prolyl-borovaline-pinacol; D010196:Pancreatic Elastase