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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

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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.

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Abbreviations

Cys:

Cysteine

CysGly:

Cysteinylglycine

Hcy:

Homocysteine

CSH:

Reduced Cys

CSSC:

Cystine

CSS-ALB:

Cysteine-albumin mixed disulfide

CGSH:

Reduced CysGly

CGSS-ALB:

Cysteinylglycine-albumin mixed disulfide

DTNB:

5,5′-Dithiobis(2-nitrobenzoic acid)

CSSH:

Cysteine-homocysteine mixed disulfide

HSH:

Reduced Hcy

HSSH:

Homocystine

HSS-ALB:

Homocysteine-albumin mixed disulfide

GSH:

Reduced glutathione

GSSG:

Glutathione disulfide

GSS-ALB:

Glutathione-albumin mixed disulfide

HS-ALB:

Reduced albumin

MLT:

Methionine loading test

MS:

Multiple sclerosis

MSH:

Mesna

MSSM:

Dimesna

NPSH:

Non-protein thiols

PSH:

Protein SH groups

TSH:

Total plasma thiols, sum of PSH and XSH

XSS-ALB:

Thiol-albumin mixed disulfides

tCys, tHcy:

Total concentration of redox species expressed as reduced equivalents, namely XSSX = 2XSH

CSVD:

Cerebral small vessels disease

XSH:

Reduced thiols

XSSX:

Disulfides

XSSR:

Mixed disulfides of low molecular weight

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Author notes

  1. Monica Ulivelli & Sabina Bartalini

    Present address: Department of Medicine, Surgery, and Neuroscience, University of Siena, 53100, Siena, Italy

Authors and Affiliations

  1. Pharmacology Unit, Department of Neuroscience, University of Siena, 53100, Siena, Italy

    Monica Ulivelli, Raffaella Priora, Danila Di Giuseppe, Lucia Coppo, Domenico Summa, Antonios Margaritis, Simona Frosali, Sabina Bartalini & Paolo Di Simplicio

  2. Stroke Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100, Siena, Italy

    Giuseppe Martini

  3. Neuroimaging and Neurointervention, Azienda Ospedaliera Universitaria Senese, 53100, Siena, Italy

    Alfonso Cerase

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  1. Monica Ulivelli
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Correspondence to Paolo Di Simplicio.

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Ulivelli, M., Priora, R., Di Giuseppe, D. et al. 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. Amino Acids 48, 1477–1489 (2016). https://doi.org/10.1007/s00726-016-2207-2

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