Abstract
Multiple sclerosis (MS) is an autoimmune disorder characterized by the degeneration of myelin and inflammation in the central nervous system. Trans sodium crocetinate (TSC), a novel synthetic carotenoid compound, possesses antioxidant, anti-inflammatory and neuroprotective effects. This study aimed to evaluate the protective effects of TSC against the development of experimental autoimmune encephalomyelitis (EAE), a well-established model for MS. Female BALB/C57 mice were divided into different groups, including control, EAE, vehicle, TSC-treated (25, 50, and 100 mg/kg, administered via gavage) + EAE, methyl prednisone acetate + EAE, and TSC-treated (100 mg/kg, administered via gavage for 28 days) groups. EAE was induced using MOG35-55, complete Freund’s adjuvant, and pertussis toxin. In the mice spinal cord tissues, the oxidative markers (GSH and MDA) were measured using spectrophotometry and histological evaluation was performed. Mitophagic pathway proteins (PINK1and PARKIN) and inflammatory factors (IL-1β and TNF-α) were evaluated by western blot. Following 21 days post-induction, EAE mice exhibited weight loss, and the paralysis scores increased on day 13 but recovered after TSC (100 mg/kg) administration on day 16. Furthermore, TSC (50 and 100 mg/kg) reversed the altered levels of MDA and GSH in the spinal cord tissue of EAE mice. TSC (100 mg/kg) also decreased microgliosis, demyelination, and the levels of inflammatory markers IL-1β and TNF-α. Notably, TSC (100 mg/kg) modulated the mitophagy pathway by reducing PINK1 and Parkin protein levels. These findings demonstrate that TSC protects spinal cord tissue against EAE-induced MS through anti-inflammatory, antioxidant, and anti-mitophagy mechanisms.
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Abbreviations
- ATG5:
-
Autophagy related 5
- CFA:
-
Freund’s Adjuvant, Complete
- CNS:
-
central nervous system
- COX-2:
-
Cyclooxygenase 2
- CQ:
-
clioquinol
- CSF:
-
cerebrospinal fluid
- Drp1:
-
Dynamin-related protein 1
- EAE:
-
Experimental Autoimmune Encephalomyelitis
- GSH:
-
Glutathione
- H&E:
-
Hematoxylin-eosin
- IL-1β:
-
Interleukin‐1β
- IL-6:
-
Interleukin 6
- iNOS:
-
Inducible nitric oxide synthase
- LC3:
-
Microtubule-associated protein 1 A/1B-light chain 3
- LFB:
-
Luxol fast blue
- MP:
-
Methyl prednisone acetate
- MDA:
-
Malondialdehyde
- MOG:
-
Myelin oligodendrocyte glycoprotein
- mRNA:
-
Messenger RNA
- MS:
-
Multiple Sclerosis
- MSIF:
-
MS International Federation
- NF-Κb:
-
nuclear transcription factor-kappa B
- PINK1:
-
Parkin and PTEN-induced kinase 1
- PTX:
-
Pertussis toxin
- PVDF:
-
Polyvinylidene fluoride
- ROS:
-
Reactive oxygen species
- SOD:
-
Superoxide dismutase
- TBST:
-
Tris-Buffered Saline and Tween 20
- TNF-α:
-
Tumor necrosis factor alpha
- TSC:
-
Trans sodium crocetinate
- TMEV:
-
Theiler׳s murine encephalomyelitis virus
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Acknowledgements
The authors are thankful to the Vice-Chancellor of Research, Mashhad University of Medical Sciences for financial support (Grant/Award Number: 971984). The results presented in this paper are part of a Ph.D. thesis.
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This work was supported by the Mashhad University of Medical Sciences. Start-up funding to A/Prof. Hossein Hosseinzadeh.
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Sara Banaeeyeh: Investigation, Data curation, Data analyses, Writing, Original draft preparation, and Editing. Zahra Moosavi: Pathology analysis. Amir Afkhami-Goli: Supervision, EAE induction, Reviewing, and Editing. Bibi Marjan Razavi: Conceptualization, Supervision, Data analyses, Reviewing and Editing. Hossein Hosseinzade: Conceptualization, Supervision, Data analyses, Reviewing and Editing. All the authors approved the final version of the manuscript.
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Banaeeyeh, S., Afkhami-Goli, A., Moosavi, Z. et al. Anti-inflammatory, antioxidant and anti-mitophagy effects of trans sodium crocetinate on experimental autoimmune encephalomyelitis in BALB/C57 mice. Metab Brain Dis (2024). https://doi.org/10.1007/s11011-024-01349-0
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DOI: https://doi.org/10.1007/s11011-024-01349-0