烯丙胺和beta-aminopropionitrile诱发主动脉中央坏死:合作机制。
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Kumar D,特伦特MB,粗野的PJ
烯丙胺和beta-aminopropionitrile诱发主动脉中央坏死:合作机制。
毒理学。1998年2月6日,125(2):107 - 15所示。
- PubMed ID
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9570326 (在PubMed]
- 文摘
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我们已经开发了一个模型的主动脉平滑肌坏死的成年雄性sd大鼠中喂食血管毒素(盐酸烯丙胺或AA, beta-aminopropionitrile或betaAPN)音乐会的10天。要么单独给予的毒素不会引起主动脉病变。为了阐明这两种毒素的协同作用的机理我们美联储知道调节器AA或betaAPN毒性大鼠同时和两个毒素。我们使用调节器(a)氨基脲(98毫克/公斤/天,鉴于之前4 h毒素),一个已知的抑制剂的血管酶SSAO代谢AA;(b)半胱氨酸(1.5%的鼠粮,毒素开始前3天),这已经被证明可以减少betaAPN的毒性作用;和(c)硫酸苯乙肼(3毫克/公斤/天,鉴于4 h毒素之前),一种抑制剂SSAO和电位器betaAPN毒性。老鼠被喂食各种组合的毒素和调节器填喂法:水(n = 8);(AA, 100毫克/公斤/天)AA +苯乙肼(n = 8);AA +氨基脲(n = 8);AA +半胱氨酸(n = 11); (betaAPN, 1 g/kg/day) betaAPN + phenelzine (n = 8); betaAPN + semicarbazide (n = 8); betaAPN + L-cysteine (n = 8); (AA, 100 mg + betaAPN, 1 g/kg/day) AA + betaAPN + phenelzine (n = 9), AA + betaAPN + semicarbazide (n = 8); AA + betaAPN + L-cysteine (n = 12); phenelzine (3 mg/kg/day) (n = 4); semicarbazide (98 mg/kg/day) (n = 4) and L-cysteine (1.5% in rat chow) (n = 4). We found that phenelzine sulphate (a drug previously used in the treatment of hypertension) when given with AA reproduced the AA + betaAPN induced aortic lesions. Phenelzine + betaAPN caused no lesions, but when combined with AA + betaAPN, aortic lesions were intensified and included marked secondary degeneration of the vascular wall. Semicarbazide was found to completely obviate the vascular toxicity of AA + betaAPN. L-Cysteine feeding markedly decreased the incidence and severity of vascular lesions in AA + betaAPN treated rats, but did not change the incidence or severity of heart lesions caused by AA alone. These data indicate that the synergistic necrotizing toxicity of AA + betaAPN is primarily an AA effect. We postulate that some modulating influence of betaAPN (or phenelzine) on tissue distribution, metabolism, or detoxification pathways of AA increases AA's acute vascular toxicity, whereas semicarbazide offers protection by inhibiting the initial deamination of AA to a highly reactive aldehyde.