EFFECTS OF OLIGOPEPTIDE CHLOROMETHYLKETONE ADMINISTERED AFTER ELASTASE - RENAL TOXICITY AND LACK OF PREVENTION OF EXPERIMENTAL EMPHYSEMA

Publisher Website
Google Scholar
Abstract
The effectiveness of N-acetyl-L-alanyl-L-alanyl-L-prolyl-L-alanine chloromethylketone (AAPACK) in preventing the development of experimental emphysema in hamsters, when administered 60 min after exposure to elastase, was studied. When 19 mg of AAPACK was injected i.p. in divided doses commencing 60 min after the intratracheal instillation of pancreatic elastase, the development of emphysema was not prevented using morphologic, morphometric and physiologic means of evaluation. Hamsters (38%) given AAPACK became ill and lost weight. At autopsy, these hamsters had a renal tubular nephropathy and focal interstitial disease. The glomeruli were spared. Hamsters (5) with renal tubular lesions had azotemia. Focal necrosis was observed in the heart of 3 and in the liver of 5 animals with renal lesions. AAPACK, in the protocol followed where elastase preceded administration of the inhibitor did not prevent the development of elastase-induced emphysema and did produce a unique renal tubular nephropathy.