Faculty of Medicine, Institute of Medical Physiology "Richard Burian", University of Belgrade, Visegradska 26/II, Belgrade, 11000, Serbia.
Military Health Department, Ministry of Defence, Belgrade, Serbia.
Mol Cell Biochem. 2019 Jan;451(1-2):43-54. doi: 10.1007/s11010-018-3391-z. Epub 2018 Jun 23.
Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways; methionine-rich diets were used to induce hyperhomocysteinemia, and cardiovascular pathology was often observed. Other sulfur amino acids interfere with this metabolism, i.e., L-cysteine (Cys) and N-aceyl-L-cysteine (NAC), and probably also affect cardiovascular system. Their effects are controversial due to their ability to act both as anti- or pro-oxidant. Thus, this study aimed to elucidate their influence on levels of homocysteine, folate and vitamin B12, levels of different haemostatic parameters (fibrinogen, D-dimer, vWF Ag, vWF Ac) in rat serum or plasma as well as their effects on cardiac and aortic tissue histology in subchronically methionine-treated rats. Wistar albino rats were divided into 4 experimental groups: (a) control group (0.9% sodium chloride 0.1-0.2 mL/day) (n = 10) (K); (b) DL-methionine (0.8 mmol/kg/bw/day) (n = 10) (M); (c) DL-methionine (0.8 mmol/kg/bw/day) + L-cysteine (7 mg/kg/bw/day) (n = 8) (C); (d) DL-methionine (0.8 mmol/ kg/bw/day) + N-acetyl-L-cysteine (50 mg/kg/bw/day) (n = 8) (N). All substances were applied i.p., treatment duration 3 weeks. Lower levels of vitamin B12 in all the groups were found. Folate was reduced only in N group. Decreased fibrinogen was noted in C and N groups and increased D-dimer only in C. VWF activity was reduced in M and C groups. Deleterious effects in heart were observed, especially after Cys and NAC application. Aortic tissue remained unchanged. In conclusion, it could be said that sulfur amino acids have the significant impact on cardiovascular system in subchronically methionine-treated rats. This study points out the relevance of their complex interactions and deleterious effects mediated by either direct influence or procoagulant properties.
蛋氨酸是同型半胱氨酸的前体，同型半胱氨酸是甲基化和转硫途径中的一种含硫氨基酸中间产物；富含蛋氨酸的饮食被用来诱导高同型半胱氨酸血症，并且经常观察到心血管病理学。其他含硫氨基酸会干扰这种代谢，即 L-半胱氨酸 (Cys) 和 N-乙酰-L-半胱氨酸 (NAC)，并且可能也会影响心血管系统。由于它们具有抗氧化或促氧化剂的双重作用，因此它们的作用存在争议。因此，本研究旨在阐明它们对同型半胱氨酸、叶酸和维生素 B12 水平、大鼠血清或血浆中不同止血参数（纤维蛋白原、D-二聚体、vWF Ag、vWF Ac）水平的影响，以及它们对亚慢性蛋氨酸处理大鼠心脏和主动脉组织病理学的影响。Wistar 白化大鼠被分为 4 个实验组：(a) 对照组（0.9%氯化钠 0.1-0.2 mL/天）（n = 10）（K）；(b) DL-蛋氨酸（0.8 mmol/kg/bw/天）（n = 10）（M）；(c) DL-蛋氨酸（0.8 mmol/kg/bw/天）+L-半胱氨酸（7 mg/kg/bw/天）（n = 8）（C）；(d) DL-蛋氨酸（0.8 mmol/kg/bw/天）+N-乙酰-L-半胱氨酸（50 mg/kg/bw/天）（n = 8）（N）。所有物质均通过腹腔注射给药，治疗持续 3 周。所有组的维生素 B12 水平均降低。仅 N 组的叶酸减少。C 和 N 组的纤维蛋白原减少，仅 C 组的 D-二聚体增加。vWF 活性在 M 和 C 组中降低。在心脏中观察到有害作用，尤其是在应用 Cys 和 NAC 后。主动脉组织保持不变。总之，可以说在亚慢性蛋氨酸处理的大鼠中，含硫氨基酸对心血管系统有重大影响。本研究指出了它们通过直接影响或促凝特性介导的复杂相互作用和有害作用的相关性。
