title: The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice.
abstract: OBJECTIVE
  Currently approved therapies for multiple sclerosis (MS) at best only slow down its progression. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In the present study, for the first time we evaluated the therapeutic potential of MSc1 nanocomplex, which was designed based on novel nanochelating technology.
  
  
  METHODS
  MSc1 cell-protection capacity, with and without iron bond, was evaluated against hydrogen peroxide (H2O2)-induced oxidative stress in cultured rat pheochromocytoma-12 cells. The ability of MSc1 to maintain iron bond at pH ranges of 1-7 was evaluated. Nanocomplex toxicity was examined by estimating the intraperitoneal median lethal dose (LD50). Experimental autoimmune encephalomyelitic mice were injected with MSc1 14 days after disease induction, when the clinical symptoms appeared. The clinical score, body weight, and disease-induced mortality were monitored until day 54. In the end, after collecting blood samples for assessing hemoglobin and red blood cell count, the brains and livers of the mice were isolated for hematoxylin and eosin staining and analysis of iron content, respectively.
  
  
  RESULTS
  The results showed that MSc1 prevented H2O2-induced cell death even after binding with iron, and it preserved its bond with iron constant at pH ranges 1-7. The nanocomplex intraperitoneal LD50 was 1,776.59 mg/kg. MSc1 prompted therapeutic behavior and improved the disabling features of experimental autoimmune encephalomyelitis, which was confirmed by decreased clinical scores versus increased body mass and 100% survival probability. It did not cause any adverse effects on hemoglobin or red blood cell count. Histopathological studies showed no neural loss or lymphocyte infiltration in MSc1-treated mice, while the hepatic iron content was also normal.
  
  
  CONCLUSIONS
  These results demonstrate that MSc1 could be a promising beneficial novel agent and has the capacity to be evaluated in further studies.
authors.affiliation: Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran.
authors.forename: Saideh
authors.initials: S
authors.lastname: Fakharzadeh
authors.affiliation: MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Sahraian
authors.affiliation: Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hafizi
authors.affiliation: Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Kalanaky
authors.affiliation: Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Masoumi
authors.affiliation: Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mahdavi
authors.affiliation: Department of Pathology, Medical School of Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nasser
authors.initials: N
authors.lastname: Kamalian
authors.affiliation: Department of Neurology, LSU Health Sciences Centre, Shreveport, LA, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Minagar
authors.affiliation: Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Nazaran
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000188:drug therapy*; D006861:Hydrogen Peroxide / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D020011:Protective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D016019:Survival Analysis
chemical_list: D007502:Iron Chelating Agents; D020011:Protective Agents; D006861:Hydrogen Peroxide; D007501:Iron
keywords: EAE; MSc1; multiple sclerosis; nanochelating technology; nanocomplex