In vitro and in vivo inhibition of lysyl oxidase by aminopropionitriles.
J Toxicol Environ Health 1992 Nov; 37(3):411-423
The inhibitory potential of aminopropionitriles towards lysyl- oxidase was investigated both in-vivo and in-vitro. The compounds tested included beta-aminopropionitrile (151188) (BAPN), 3,3'- dimethylaminopropionitrile (DMAPN), 3,3'-iminodipropionitrile (111944) (IDPN), and monomethylaminopropionitrile (MMAPN). Lysyl- oxidase inhibition was determined in-vitro by incubating various concentrations of each compound with supernatant obtained from chick embryo leg bones and radiolabeled chick embryo aorta substrate. In- vivo inhibition experiments were conducted on male Sprague-Dawley- rats administered 400mg/kg BAPN, 100mg/kg MMAPN, 250mg/kg DMAPN, or 300mg/kg IDPN by intraperitoneal injection for 4 days. A second group was pretreated with pargyline before receiving the same dosage regimen. Incubation of BAPN, IDPN, and MMAPN with chick embryo leg bone supernatant resulted in inhibition of the lysyl-oxidase catalyzed release of tritium from labeled aortic substrate. DMAPN was a significantly less potent inhibitor of lysyl-oxidase. BAPN and IDPN induced irreversible inhibition of lysyl-oxidase but DMAPN and MMAPN did not. Rats treated with BAPN exhibited a significant decrease in lysyl-oxidase activity compared to controls. Pretreatment with pargyline increased slightly the BAPN induced inhibition of lysyl-oxidase. Animals treated with IDPN had a small but insignificant decrease in lysyl-oxidase activity. The authors conclude that the presence of a primary amino functional group in aminopropionitriles is not a condition necessary for inhibition of lysyl-oxidase. Additionally, reversible and irreversible inhibition mechanisms may be associated with osteolathyric changes induced by IDPN exposure.
NIOSH-Publication; NIOSH-Grant; Training; Comparative-toxicology; Connective-tissue; Enzyme-activity; Enzyme-inhibitors; In-vitro-study; In-vivo-study; Laboratory-animals; Nitriles; Toxic-effects
Inst of Safety & Systems Mgmt University of California University Park Los Angeles, Calif 90089-0021
Journal of Toxicology and Environmental Health
University of Southern California, Los Angeles, California