PMID- 32256946
OWN - NLM
STAT- MEDLINE
DCOM- 20201216
LR  - 20201216
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2020
DP  - 2020
TI  - Cladribine Treatment Improved Homocysteine Metabolism and Increased Total Serum 
      Antioxidant Activity in Secondary Progressive Multiple Sclerosis Patients.
PG  - 1654754
LID - 10.1155/2020/1654754 [doi]
LID - 1654754
AB  - Hyperhomocysteinemia plays a crucial role in the pathogenesis of many diseases of 
      the central nervous system (CNS). The nervous system is particularly sensitive to 
      high homocysteine (Hcy) level mainly due to its prooxidative and cytotoxic 
      effects. Cladribine, a drug recently registered for the treatment of multiple 
      sclerosis (MS), possesses additionally neuroprotective effects which are 
      independent of its peripheral immunosuppressant action. Accumulating evidence 
      suggests that oxidative stress and homocysteine thiolactone-mediated protein 
      homocysteinylation play a causal role in MS. Both of these processes may be 
      attenuated by paraoxonase 1 (PON1). Therefore, in the present study, we aimed to 
      examine whether the beneficial effects of the drug in MS patients with a 
      secondary progressive (SP) clinical course, treated with cladribine 
      subcutaneously (s.c.), may be related to its ability to modify serum PON1 
      activity, Hcy concentration, and protein homocysteinylation, as well as to 
      correct total antioxidant status. A total of 118 subjects were enrolled into the 
      study: (1) patients with a SP type of MS, SP-MS (n = 40); (2) patients with a 
      relapsing-remitting (RR) type of MS, RR-MS (n = 30); and (3) healthy people (n = 
      48). Patients with SP-MS were treated with cladribine. The drug was given in 
      SP-SM patients s.c. six times every 6 weeks up to a total mean cumulative dose of 
      1.8 mg/kg. PON1 activity was assessed spectrophotometrically. The level of Hcy, 
      homocysteine thiolactone (HTL) attached to plasma proteins (N-Hcy-protein), and 
      antibodies against homocysteinylated proteins was assessed with an enzyme 
      immunoassay. The total antioxidant activity of the serum was assessed with the 
      ferric-reducing activity of plasma (FRAP) method. Basically, there was no 
      difference in PON1 activity between untreated SP-MS, RR-MS, and control subjects. 
      Serum Hcy was significantly higher in RR-MS patients (p < 0.001) and in SP-MS 
      patients (p < 0.01) compared to the control group. The N-Hcy protein level was 
      higher in RR-MS patients (p < 0.05) in comparison to the control group. Moreover, 
      the elevated level of antibodies against homocysteinylated proteins was observed 
      in the serum of patients with SP-MS. The total antioxidant capacity of serum was 
      lower in MS patients vs. the control group (p < 0.001). After cladribine 
      treatment, the activity of PON1 did not change in SP-MS patients, whereas 
      cladribine treatment decreased the level of total Hcy (p < 0.05). Treatment with 
      cladribine increased the total serum antioxidant activity in SP-MS patients (p < 
      0.01). The Expanded Disability Status Scale (EDSS) score did not change in SP-MS 
      patients. Cladribine treatment in the SP-MS group attenuates 
      hyperhomocysteinemia-induced protein homocysteinylation (n.s.). It also 
      stabilises the neurological condition of SP-MS patients. The stabilisation of a 
      neurological condition observed in SP-MS patients after cladribine treatment may 
      be partially related to its ability to reduce elevated Hcy level and to improve 
      serum antioxidant potential.
CI  - Copyright (c) 2020 Anna Jamroz-Wisniewska et al.
FAU - Jamroz-Wisniewska, Anna
AU  - Jamroz-Wisniewska A
AUID- ORCID: 0000-0002-2905-3777
AD  - Department of Neurology of Lublin Medical University, Lublin, Poland.
FAU - Beltowski, Jerzy
AU  - Beltowski J
AD  - Department of Pathophysiology of Lublin Medical University, Lublin, Poland.
FAU - Wojcicka, Grazyna
AU  - Wojcicka G
AD  - Department of Pathophysiology of Lublin Medical University, Lublin, Poland.
FAU - Bartosik-Psujek, Halina
AU  - Bartosik-Psujek H
AD  - Department of Neurology of Rzeszow University, Rzeszow, Poland.
FAU - Rejdak, Konrad
AU  - Rejdak K
AD  - Department of Neurology of Lublin Medical University, Lublin, Poland.
LA  - eng
PT  - Journal Article
DEP - 20200314
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antioxidants)
RN  - 47M74X9YT5 (Cladribine)
SB  - IM
MH  - Adult
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Antioxidants/*metabolism
MH  - Cladribine/pharmacology/*therapeutic use
MH  - Female
MH  - Humans
MH  - Hyperhomocysteinemia/*drug therapy
MH  - Male
MH  - Multiple Sclerosis, Relapsing-Remitting/*drug therapy/pathology
PMC - PMC7103043
COIS- The authors declare no financial or other conflicts of interest.
EDAT- 2020/04/08 06:00
MHDA- 2020/12/17 06:00
PMCR- 2020/03/14
CRDT- 2020/04/08 06:00
PHST- 2019/11/11 00:00 [received]
PHST- 2020/02/02 00:00 [revised]
PHST- 2020/02/18 00:00 [accepted]
PHST- 2020/04/08 06:00 [entrez]
PHST- 2020/04/08 06:00 [pubmed]
PHST- 2020/12/17 06:00 [medline]
PHST- 2020/03/14 00:00 [pmc-release]
AID - 10.1155/2020/1654754 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2020 Mar 14;2020:1654754. doi: 10.1155/2020/1654754. 
      eCollection 2020.