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Amino Acids

, Volume 47, Issue 9, pp 1837–1845 | Cite as

Serum and cerebrospinal fluid concentrations of homoarginine, arginine, asymmetric and symmetric dimethylarginine, nitrite and nitrate in patients with multiple sclerosis and neuromyelitis optica

  • Aiden HaghikiaEmail author
  • Arslan Arinc Kayacelebi
  • Bibiana Beckmann
  • Erik Hanff
  • Ralf Gold
  • Arash Haghikia
  • Dimitrios Tsikas
Original Article
Part of the following topical collections:
  1. Homoarginine, Arginine and Relatives

Abstract

The pathogenic hallmarks of multiple sclerosis (MS) and neuromyelitis optica (NMO) are cellular and humoral inflammatory infiltrates and subsequent demyelination, or astrocytic cell death in NMO, respectively. These processes are accompanied by disruption of the blood–brain barrier as regularly observed by gadolinium enhancement on magnetic resonance imaging. The role of the l-arginine/nitric oxide (NO) pathway in the pathophysiology of neuroinflammatory diseases, such as MS and NMO, remains unclear. In the present study, we measured the concentrations of the nitric oxide (NO) metabolites nitrate and nitrite, the endogenous substrates of NO synthase (NOS) l-arginine (Arg) and l-homoarginine (hArg), and asymmetric dimethylarginine (ADMA), the endogenous inhibitor of NOS activity, in the serum and cerebrospinal fluid (CSF) of patients with MS, NMO or other neurologic diseases (OND). MS (551 ± 23 nM, P = 0.004) and NMO (608 ± 51 nM, P = 0.006) patients have higher ADMA concentrations in serum than healthy controls (HC; 430 ± 24 nM). For MS, this finding was confirmed in CSF (685 ± 100 nM in relapsing–remitting multiple sclerosis, RRMS; 597 ± 51 nM in secondary progressive multiple sclerosis, SPMS) compared with OND (514 ± 37 nM; P = 0.003). Serum concentrations of Arg (61.1 ± 9.7 vs. 63.6 ± 4.9 µM, P = 0.760), hArg (2.62 ± 0.26 vs. 2.52 ± 0.23 µM, P = 0.891), nitrate (38.1 ± 2.2 vs. 38.1 ± 3.0 µM) and nitrite (1.37 ± 0.09 vs. 1.55 ± 0.03 µM) did not differ between MS and OND. Also, CSF concentrations of hArg (0.685 ± 0.100 µM in RRMS, 0.597 ± 0.051 µM in SPMS, 0.514 ± 0.037 µM in OND), nitrate (11.3 ± 0.6 vs. 10.5 ± 0.3 µM) and nitrite (2.84 ± 0.32 vs. 2.41 ± 0.11 µM) did not differ between the groups. In NMO patients, however, serum Arg (117 ± 11 vs. 64 ± 4.9 μM, P = 0.004), nitrate (29 ± 2.1 vs. 38 ± 3 μM, P = 0.03), and nitrite (1.09 ± 0.02 vs. 1.55 ± 0.033 µM, P < 0.0001) were significantly different as compared to OND. Symmetric dimethylarginine (SDMA) concentration did not differ in serum between MS and HC (779 ± 43 vs. 755 ± 58 nM, P = 0.681) or in CSF between MS and OND patients (237 ± 11 vs. 230 ± 17 nM, P = 0.217). Our study suggests a potential role for ADMA and Arg in neuroinflammatory diseases with diverse functions in MS and NMO. Higher ADMA synthesis may explain reduced NO availability in NMO. hArg and SDMA seem not to play an important role in MS and NMO.

Keywords

ADMA Arginine NO Cerebrospinal fluid Homoarginine Multiple sclerosis Neuromyelitis optica 

Abbreviations

ADMA

Asymmetric dimethylarginine (N G, N G-dimethyl-l-arginine)

AGAT

Arginine:glycine amidinotransferase

AQP

Aquaporin

CNS

Central nervous system

CSF

Cerebrospinal fluids

GC–MS

Gas chromatography–mass spectrometry

GC–MS/MS

Gas chromatography–tandem mass spectrometry

hArg

Homoarginine

HC

Healthy controls

MS

Multiple sclerosis

NMO

Neuromyelitis optica

NO

Nitric oxide

NOS

Nitric oxide synthase

OND

Other neurologic diseases

RRMS

Relapsing–remitting multiple sclerosis

SDMA

Symmetric dimethylarginine (N G, N G′-dimethyl-l-arginine)

SPMS

Secondary progressive multiple sclerosis

Notes

Conflict of interest

The authors declare that they have no conflict of interest related to the present research.

Ethical standard

The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in an approval by the Ethics Committee of the Ruhr-University Bochum (Bochum, Germany).

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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Aiden Haghikia
    • 1
    Email author
  • Arslan Arinc Kayacelebi
    • 2
  • Bibiana Beckmann
    • 2
  • Erik Hanff
    • 2
  • Ralf Gold
    • 1
  • Arash Haghikia
    • 3
  • Dimitrios Tsikas
    • 2
  1. 1.Department of NeurologySt. Josef-Hospital, Ruhr-UniversityBochumGermany
  2. 2.Centre of Pharmacology and ToxicologyHannover Medical SchoolHannoverGermany
  3. 3.Department of Cardiology and AngiologyHannover Medical SchoolHannoverGermany

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