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Allylamine-induced vascular toxicity in vitro: prevention by semicarbazide-sensitive amine oxidase inhibitors.

Abstract：

:The present studies were designed to evaluate the role that metabolic activation plays in allylamine (AAM)-induced vascular toxicity. The effects of AAM were evaluated in primary cultures of rat vascular endothelial (VEC) and smooth muscle cells (SMC). Semicarbazide (SC) and diethyldithiocarbamate (DDC) were used as inhibitors of semicarbazide-sensitive amine oxidase (SSAO). Clorgyline and pargyline were used as inhibitors of monoamine oxidase (MAO) A and B, respectively. The effect of catalase, a hydrogen peroxide scavenger, on AAM-induced cytotoxicity was also evaluated. Lactate dehydrogenase (LDH) release and morphological alterations were chosen as indicators of cytotoxicity. Confluent cultures of VEC and SMC were exposed to various concentrations of AAM (2-200 microM) in the absence and presence of serum for 4, 12, or 24 hr. High concentrations of AAM (200 microM) alone produced a time-dependent increase in LDH release and morphologic alterations in cultures of both cell types. Lower concentrations of AAM did not compromise the structural integrity of the cells. Semicarbazide (200 microM) or DDC (2 mM), but not clorgyline (10 microM) or pargyline (10 microM), prevented the toxicity of AAM (200 microM). Allylamine-induced cytotoxicity was partially prevented by catalase (2500 U/ml). The presence of fetal bovine serum in the medium was not essential for the manifestation of cytotoxicity. Single cell suspensions of VEC or SMC formed acrolein (ACR) when incubated in the presence of AAM. The formation of ACR mediated by SMC was inhibited by SC (20 microM), but not clorgyline (10 microM). These results support the concept that AAM is oxidatively deaminated by an SSAO present in vascular cells to generate toxic metabolic by-products capable of causing extensive cellular injury.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Ramos K,Grossman SL,Cox LR

doi

10.1016/s0041-008x(88)80008-5

subject

Has Abstract

pub_date

1988-08-01 00:00:00

pages

61-71

issue

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(88)80008-5

journal_volume

pub_type

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Allylamine-induced vascular toxicity in vitro: prevention by semicarbazide-sensitive amine oxidase inhibitors.