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In vitro and in vivo inhibition of lysyl oxidase by aminopropionitriles



Details

  • Personal Author:
  • Description:
    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. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    0098-4108
  • Document Type:
  • Funding:
  • Genre:
  • Place as Subject:
  • CIO:
  • Topic:
  • Location:
  • Pages in Document:
    411-423
  • Volume:
    37
  • Issue:
    3
  • NIOSHTIC Number:
    nn:00211279
  • Citation:
    J Toxicol Environ Health 1992 Nov; 37(3):411-423
  • Contact Point Address:
    Inst of Safety & Systems Mgmt University of California University Park Los Angeles, Calif 90089-0021
  • CAS Registry Number:
  • Federal Fiscal Year:
    1993
  • Performing Organization:
    University of Southern California, Los Angeles, California
  • Peer Reviewed:
    True
  • Start Date:
    19840701
  • Source Full Name:
    Journal of Toxicology and Environmental Health
  • End Date:
    19940630
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:fecc2af34523379fa715bf119a72ee88812cea2d655ab3b889d9b2967795521afd07124f0e809fef6927eb3891b8d22d586839f03db9c68797a03a6311753611
  • Download URL:
  • File Type:
    Filetype[PDF - 939.01 KB ]
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