A. A. Chulanova, A. M. Smakhtina, Galina S. Mal, I. Bobyntsev, E. Mishina, M. Y. Smakhtin, Pavel M. Kopeykin, Elena G. Bogomolova
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引用次数: 0
摘要
简介众所周知,在肽分子结构中加入 D-氨基酸可延长其半衰期。药用药物 Thymogen 在分子的 N 端和 C 端加入了 D-丙氨酸。调查的目的是研究胸腺肽原结构类似物对大鼠肼中毒性肝损伤的修复和抗氧化活性:研究对象为 40 只 Wistar 大鼠。通过腹腔注射 50 毫克/千克剂量的盐酸肼来模拟急性中毒性肝损伤。在中毒后的 5 天内,以等摩尔剂量腹腔注射胸腺肽原及其改良的 D-Ala 类似物。最后一次给药 12 小时后,将动物从实验中移出:已证实胸腺肽结构类似物的修复和抗氧化活性在肼损伤肝脏的情况下会增加。与胸腺肽相比,插入 D-Ala 的肽能更显著地降低自由基反应的水平。所有肽都能显著提高血浆和肝匀浆中过氧化氢酶的活性:结论:在胸腺肽分子的 N 端和 C 端加入 D-Ala 修饰的胸腺肽类似物可被视为具有开发新型保肝药物前景的药理物质。
Protective effects of thymogen analogues, modified by D-alanine, in hydrazine liver damage
Introduction: It is known that the insertion of D-amino acids into the structure of a peptide molecule can increase its half-life. The pharmacological drug Thymogen was modified with D-alanine from the N- and C-terminus of the molecule. The aim of the investigation was to study the reparative and antioxidant activity of structural analogues of thymogen in toxic liver damage by hydrazine in rats.
Materials and Methods: The investigation was conducted on 40 Wistar rats. Acute toxic liver damage was simulated with a single intraperitoneal injection of hydrazine hydrochloride at a dose of 50 mg/kg. Thymogen and its modified D-Ala analogues were administered intraperitoneally in equimolar doses for 5 days after intoxication. The animals were removed from the experiment 12 hours after the final administration of the peptides.
Results and Discussion: It has been established the reparative and antioxidant activities of thymogen structural analogues increased in conditions of liver damage with hydrazine. Peptides with the insertion of D-Ala reduced the level of free radical reactions more significantly in comparison with thymogen. All peptides comparably increased catalase activity in blood plasma and liver homogenate.
Conclusion: Thymogen analogues modified with D-Ala from the N- and C-terminus of the molecule can be considered as promising pharmacological substances for the development of new hepatoprotective drugs.