In vitro and in vivo inhibition of lysyl oxidase by aminopropionitriles
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1992/11/01
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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]
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ISSN:0098-4108
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Pages in Document:411-423
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Volume:37
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Issue:3
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NIOSHTIC Number:nn:00211279
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Citation:J Toxicol Environ Health 1992 Nov; 37(3):411-423
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Contact Point Address:Inst of Safety & Systems Mgmt University of California University Park Los Angeles, Calif 90089-0021
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CAS Registry Number:
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Federal Fiscal Year:1993
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Performing Organization:University of Southern California, Los Angeles, California
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Peer Reviewed:True
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Start Date:19840701
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Source Full Name:Journal of Toxicology and Environmental Health
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End Date:19940630
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Main Document Checksum:urn:sha-512:fecc2af34523379fa715bf119a72ee88812cea2d655ab3b889d9b2967795521afd07124f0e809fef6927eb3891b8d22d586839f03db9c68797a03a6311753611
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