title: Homocysteinemia control by cysteine in cerebral vascular patients after methionine loading test: evidences in physiological and pathological conditions in cerebro-vascular and multiple sclerosis patients.
abstract: The toxicity risk of hyperhomocysteinemia is prevented through thiol drug administration which reduces plasma total homocysteine (tHcy) concentrations by activating thiol exchange reactions. Assuming that cysteine (Cys) is a homocysteinemia regulator, the hypothesis was verified in healthy and pathological individuals after the methionine loading test (MLT). The plasma variations of redox species of Cys, Hcy, cysteinylglycine, glutathione and albumin (reduced, HS-ALB, and at mixed disulfide, XSS-ALB) were compared in patients with cerebral small vessels disease (CSVD) (n = 11), multiple sclerosis (MS) (n = 12) and healthy controls (n = 11) at 2-4-6 h after MLT. In MLT-treated subjects, the activation of thiol exchange reactions provoked significant changes over time in redox species concentrations of Cys, Hcy, and albumin. Significant differences between controls and pathological groups were also observed. In non-methionine-treated subjects, total Cys concentrations, tHcy and thiol-protein mixed disulfides (CSS-ALB, HSS-ALB) of CSVD patients were higher than controls. After MLT, all groups displayed significant cystine (CSSC) increases and CSS-ALB decreases, that in pathological groups were significantly higher than controls. These data would confirm the Cys regulatory role on the homocysteinemia; they also explain that the Cys-Hcy mixed disulfide excretion is an important point of hyperhomocysteinemia control. Moreover, in all groups after MLT, significant increases in albumin concentrations, named total albumin (tALB) and measured as sum of HS-ALB (spectrophometric), and XSS-ALB (assayed at HPLC) were observed. tALB increases, more pronounced in healthy than in the pathological subjects, could indicate alterations of albumin equilibria between plasma and other extracellular spaces, whose toxicological consequences deserve further studies.
authors.affiliation: Department of Medicine, Surgery, and Neuroscience, University of Siena, 53100, Siena, Italy.|Pharmacology Unit, Department of Neuroscience, University of Siena, 53100, Siena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Ulivelli
authors.affiliation: Pharmacology Unit, Department of Neuroscience, University of Siena, 53100, Siena, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Priora
authors.affiliation: Pharmacology Unit, Department of Neuroscience, University of Siena, 53100, Siena, Italy.
authors.forename: Danila
authors.initials: D
authors.lastname: Di Giuseppe
authors.affiliation: Pharmacology Unit, Department of Neuroscience, University of Siena, 53100, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Coppo
authors.affiliation: Pharmacology Unit, Department of Neuroscience, University of Siena, 53100, Siena, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Summa
authors.affiliation: Pharmacology Unit, Department of Neuroscience, University of Siena, 53100, Siena, Italy.
authors.forename: Antonios
authors.initials: A
authors.lastname: Margaritis
authors.affiliation: Pharmacology Unit, Department of Neuroscience, University of Siena, 53100, Siena, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Frosali
authors.affiliation: Department of Medicine, Surgery, and Neuroscience, University of Siena, 53100, Siena, Italy.|Pharmacology Unit, Department of Neuroscience, University of Siena, 53100, Siena, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Bartalini
authors.affiliation: Stroke Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100, Siena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Martini
authors.affiliation: Neuroimaging and Neurointervention, Azienda Ospedaliera Universitaria Senese, 53100, Siena, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cerase
authors.affiliation: Pharmacology Unit, Department of Neuroscience, University of Siena, 53100, Siena, Italy. disimplicio@unisi.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Simplicio
mesh_terms: D000328:Adult; D002561:Cerebrovascular Disorders / Q000097:blood / Q000503:physiopathology; D003545:Cysteine / Q000097:blood*; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000503:physiopathology; D008297:Male; D008715:Methionine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000503:physiopathology; D000075462:Serum Albumin, Human / Q000378:metabolism
chemical_list: D006710:Homocysteine; D008715:Methionine; D003545:Cysteine; D000075462:Serum Albumin, Human
keywords: Cerebral vascular diseases; Cysteine; Homocysteine; Methionine loading test; Plasma thiols