The effects of l-cysteine and N-acetyl-l-cysteine on homocysteine metabolism and haemostatic markers, and on cardiac and aortic histology in subchronically methionine-treated Wistar male rats

• Published in: Molecular and cellular biochemistry 2019-01, Vol.451 (1-2), p.43-54
• Main Authors: Kostic, Sanja, Micovic, Zarko, Andrejevic, Lazar, Cvetkovic, Sasa, Stamenkovic, Aleksandra, Stankovic, Sanja, Obrenovic, Radmila
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Acetylcysteine - pharmacology; Amino acids; Animals; Aorta; Aorta - cytology; Aorta - drug effects; Aorta - metabolism; Biochemistry; Biomarkers - metabolism; Biomedical and Life Sciences; Cardiology; Cardiovascular pathology; Cardiovascular system; Cyanocobalamin; Cysteine; Cysteine - pharmacology; Dimers; Fibrinogen; Folic acid; Heart; Heart - drug effects; Heart - physiology; Hemostatics; Histology; Homocysteine; Homocysteine - metabolism; Hyperhomocysteinemia; Life Sciences; Male; Medical Biochemistry; Metabolism; Methionine; Methionine - administration & dosage; Methylation; Oncology; Oxidizing agents; Rats; Rats, Wistar; Sodium chloride; Sulfur; Vitamin B12
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-018-3391-z

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.