Effects of oligopeptide chloromethylketone administered after elastase: renal toxicity and lack of prevention of experimental emphysema

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 intraperitoneally 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. Thirty-eight per cent of hamsters given AAPACK became ill and lost weight. At autopsy, these hamsters had a renal tubular nephropathy and focal interstitial disease. The glomeruli were spared. Five of these hamsters 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. These studies indicated that AAPACK, in the protocol followed where elastase precedes administration of the inhibitor, (1) does not prevent the development of elastase-induced emphysema, and (2) does produce a unique renal tubular nephropathy.