Voprosy meditsinskoi khimii (ISSN 0042-8809)

Influences of semicarbazide-sensitive amine oxidase activity and cellular glutathione upon cytotoxic effects of allylamine, acrolein and formaldehyde in human cultured endothelial cells

   
Pino R., Lyles G.A.
PubMed Id: 9503571
Year: 1997 vol: 43  issue:6  pages: 537-547
Abstract: The ability of allylamine (AA) administration to produce vascular lesions resembling atherosclerotic disease in animals, has been linked to metabolism of AA to the toxic aldehyde acrolein (ACR) by a semicarbazide-sensitive amine oxidase (SSAO) found in plasma and in vascular smooth muscle. Here, we have assessed the cytotoxicity of AA and ACR towards cultured human umbilical vein endothelial cells (HUVEC). After 20h treatment, 50 microM AA alone had no effect and 100 microM AA produced a modest reduction in cell viability. However, both concentrations produced considerable cell death when incubated with HUVEC in the presence of human umbilical artery homogenate as a source of human vascular SSAO activity. The cytotoxic actions of 50 microM AA were not altered by coincubation with 100 microM pargyline (an inhibitor of monoamine oxidase, MAO) but were completely prevented by 100 microM semicarbazide (SSAO inhibitor) and propargylamine (MAO/SSAO inhibitor). ACR at 50 and 100 microM was considerably cytotoxic, but had little effect at 5 and 10 microM. Since SSAO can also metabolize the biogenic aliphatic amine methylamine to formaldehyde (FA), effects of this aldehyde upon HUVEC were also studied. 50 microM FA did not significantly alter HUVEC viability whereas 200 microM FA produced a small but significant reduction in viability. However, 200 microM FA (but not 50 microM FA) was highly cytotoxic in HUVEC pretreated for 24h with the glutathione (GSH) synthesis inhibitor, D.L-buthionine sulphoximine (200 microM). These results suggest that endothelial integrity or function in blood vessels could be affected by these aliphatic aldehydes as environmental pollutants, dietary contaminants, and possible products of metabolic pathways, including those involving the action of SSAO upon biogenic and xenobiotic aliphatic amines. The availability of GSH-dependent mechanisms for metabolizing these aldehydes may have an important protective influence.
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Reference: Pino R., Lyles G.A., Influences of semicarbazide-sensitive amine oxidase activity and cellular glutathione upon cytotoxic effects of allylamine, acrolein and formaldehyde in human cultured endothelial cells, Voprosy meditsinskoi khimii, 1997, vol: 43(6), 537-547.
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