The effect of the specific elastase inhibitor, alanyl alanyl prolyl alanine chloromethylketone, on elastase-induced emphysema.
The chloromethylketone derivative of the tetrapeptide, alanyl alanyl prolyl alanine significantly diminishes the extent of experimental elastase-induced emphysema in hamsters. A total of 19 mg of alanyl alanyl prolyl alanine chloromethylketone was administered intraperitoneally in divided doses before and immediately after intratracheal instillation of a standard dose (4 units) of porcine pancreatic elastase. Morphologic evaluation and measurement of mean linear intercept, internal surface area, and lung volume performed 7, 45, and 120 days after exposure to elastase indicated a marked decrease in the extent of emphysema in the group treated with alanyl alanyl prolyl alanine chloromethylketone compared with the control group. Lung elastin content determined biochemically confirmed the preservation of elastin in the hamsters treated with alanyl alanyl prolyl alanine chloromethylketone. At postmortem examination by light microscopy, no pathologic abnormalities were observed in the organs of hamsters treated with alanyl alanyl prolyl alanine chloromethylketone. These data indicate that alanyl alanyl prolyl alanine chloromethylketone in the doses administered (1) had significant anti-elastase activity in vivo; (2) markedly decreased the extent of elastase-induced emphysema; and (3) produced no adverse toxic effect during the period covered by this study protocol.
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D003094:Collagen / Q000032:analysis; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000032:analysis; D006909:Hydroxyproline / Q000032:analysis; D008168:Lung / Q000032:analysis / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D011656:Pulmonary Emphysema / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control
D000590:Amino Acid Chloromethyl Ketones; D003094:Collagen; D004549:Elastin; D010196:Pancreatic Elastase; D006909:Hydroxyproline