Vascular amine oxidase activities during synergistic vasculotoxicity

Allylamine (AA) and β-aminopropionitrile (βAPN) are well known vascular toxins with a demonstrated synergistic toxic effect, i.e. given together they cause extensive smooth muscle cell necrosis of the aortic media. In this study, we investigated the possibility that the enzymes involved in the separate toxicity of AA (semicarbazide-sensitive amine oxidase, or SSAO) and βAPN (lysyl oxidase, or LyO), could be the target(s) of their synergistic toxicity. Adult male Sprague-Dawley rats were given AA alone (AA), 100 mg/kg/day, βAPN alone (βAPN), 1 g/kg/day, or both chemicals (AA + βAPN) by gavage for 1, 2, 5 or 10 days. SSAO and LyO were assayed in aorta, lung, and bone. SSAO activity in aortas of rats treated with AA + βAPN showed a maximal decrease (40%) at 10 days; more moderate depression of SSAO was seen in lung and bone. LyO changes were most marked in aorta, where activities were consistently and markedly depressed in all rats receiving βAPN (either alone or in combined treatment). Similarly, the lung and bone LyO activity was depressed at all time points in rats receiving βAPN, but to an apparently lesser degree than in aorta. The most striking changes in in vivo enzyme activities were seen in the aorta, the major target organ in this model. No synergistic effect of the two toxins was seen in the depression of LyO enzyme activity, since there was no difference in the degree of enzyme inhibition present between rats given βAPN alone or AA + βAPN, indicating that inhibition of this enzyme is mainly due to the effect of βAPN. We suggest that AA is the primary toxin in this synergistic vasculotoxic effect. It is likely that some effect of βAPN on AA metabolism or detoxification mechanisms results in synergism.