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Treatment of a multiple sclerosis animal model by a novel nanodrop formulation of a natural antioxidant.

Binyamin O, Larush L, Frid K, Keller G, Friedman-Levi Y, Ovadia H, Abramsky O, Magdassi S, Gabizon R - Int J Nanomedicine (2015)

Bottom Line: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress.Pathological examinations revealed that Nano-PSO administration dramatically reduced demyelination and oxidation of lipids in the brains of the affected animals, which are hallmarks of this severe neurological disease.On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.

ABSTRACT
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress. In this work, we administered a nanodroplet formulation of pomegranate seed oil (PSO), denominated Nano-PSO, to mice induced for experimental autoimmune encephalomyelitis (EAE), an established model of MS. PSO comprises high levels of punicic acid, a unique polyunsaturated fatty acid considered as one of the strongest natural antioxidants. We show here that while EAE-induced mice treated with natural PSO presented some reduction in disease burden, this beneficial effect increased significantly when EAE mice were treated with Nano-PSO of specific size nanodroplets at much lower concentrations of the oil. Pathological examinations revealed that Nano-PSO administration dramatically reduced demyelination and oxidation of lipids in the brains of the affected animals, which are hallmarks of this severe neurological disease. We propose that novel formulations of natural antioxidants such as Nano-PSO may be considered for the treatment of patients suffering from demyelinating diseases. On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration.

No MeSH data available.


Related in: MedlinePlus

Pathological markers of EAE in Nano-PSO treated and untreated mice.Notes: Nano-PSO treated and untreated mice were sacrificed 3 weeks after induction of EAE, and their formalin-fixed, paraffin-embedded brain sections as well as those of age-matched naïve mice (C and J) were stained by mAb EO6 (A–D and F), H&E (E and G), and LFB/PAS (brains and spinal cords) (H–J). (D) and (F) represent an enlargement of the squares in (A) and (B); (E) and (G) are serial sections of (D) and (F), respectively. Arrows in (D–G) indicate immune infiltrates. Arrows in (H) represent demyelinated areas.Abbreviations: EAE, experimental autoimmune encephalomyelitis; PSO, pomegranate seed oil; mAb, monoclonal antibody; H&E, hematoxylin and eosin; LFB, Luxol fast blue; PAS, periodic acid Schiff.
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f6-ijn-10-7165: Pathological markers of EAE in Nano-PSO treated and untreated mice.Notes: Nano-PSO treated and untreated mice were sacrificed 3 weeks after induction of EAE, and their formalin-fixed, paraffin-embedded brain sections as well as those of age-matched naïve mice (C and J) were stained by mAb EO6 (A–D and F), H&E (E and G), and LFB/PAS (brains and spinal cords) (H–J). (D) and (F) represent an enlargement of the squares in (A) and (B); (E) and (G) are serial sections of (D) and (F), respectively. Arrows in (D–G) indicate immune infiltrates. Arrows in (H) represent demyelinated areas.Abbreviations: EAE, experimental autoimmune encephalomyelitis; PSO, pomegranate seed oil; mAb, monoclonal antibody; H&E, hematoxylin and eosin; LFB, Luxol fast blue; PAS, periodic acid Schiff.

Mentions: To test if the lower clinical scores resulting from Nano-PSO treatment of EAE-induced mice are consistent with reduced appearance of EAE pathological markers, we looked in the brains of treated and untreated mice for several parameters, such as infiltration of immune cells, demyelination, and lipid oxidation. Figure 6 shows that while immune infiltrates can be detected in both treated and untreated EAE brains (sections E and G), Nano-PSO administration significantly reduced lipid oxidation levels (sections A and B and enlarged in D and F), as detected by the EO6 antibody staining in both treated and untreated brains. As opposed to EAE mice, no EO6 immunostaining (section C) or immune infiltrates (not shown) could be observed in naïve mice. Nano-PSO administration also reduced demyelination levels, as can be seen by comparing Luxol fast blue staining for myelin in both brains and spinal cords of untreated, EAE and naïve mice (section H–J). Interestingly, while the EO6 antibody recognized in the untreated mice both a diffuse and a light staining as well as focal points stained intensely (section D), the latter one reminiscent of the plaques in the patients with MS,6 in the Nano-PSO-treated EAE brains, only the light and diffuse pattern of immunostaining was apparent (section F). Quantification of the levels of EO6 stain was performed by measuring the positive area in six different fields at a magnification ×40. Stained pixels were measured using image pro analyzer 3D software, Media Cybernetics (“Materials and methods” section). The quantification results show that while for EAE-treated sections the percentage of positive area was 1.11±0.08, for the nontreated samples, it was 5.17±1.13 and for the wild-type brains 0.07±0.03.


Treatment of a multiple sclerosis animal model by a novel nanodrop formulation of a natural antioxidant.

Binyamin O, Larush L, Frid K, Keller G, Friedman-Levi Y, Ovadia H, Abramsky O, Magdassi S, Gabizon R - Int J Nanomedicine (2015)

Pathological markers of EAE in Nano-PSO treated and untreated mice.Notes: Nano-PSO treated and untreated mice were sacrificed 3 weeks after induction of EAE, and their formalin-fixed, paraffin-embedded brain sections as well as those of age-matched naïve mice (C and J) were stained by mAb EO6 (A–D and F), H&E (E and G), and LFB/PAS (brains and spinal cords) (H–J). (D) and (F) represent an enlargement of the squares in (A) and (B); (E) and (G) are serial sections of (D) and (F), respectively. Arrows in (D–G) indicate immune infiltrates. Arrows in (H) represent demyelinated areas.Abbreviations: EAE, experimental autoimmune encephalomyelitis; PSO, pomegranate seed oil; mAb, monoclonal antibody; H&E, hematoxylin and eosin; LFB, Luxol fast blue; PAS, periodic acid Schiff.
© Copyright Policy
Related In: Results  -  Collection

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f6-ijn-10-7165: Pathological markers of EAE in Nano-PSO treated and untreated mice.Notes: Nano-PSO treated and untreated mice were sacrificed 3 weeks after induction of EAE, and their formalin-fixed, paraffin-embedded brain sections as well as those of age-matched naïve mice (C and J) were stained by mAb EO6 (A–D and F), H&E (E and G), and LFB/PAS (brains and spinal cords) (H–J). (D) and (F) represent an enlargement of the squares in (A) and (B); (E) and (G) are serial sections of (D) and (F), respectively. Arrows in (D–G) indicate immune infiltrates. Arrows in (H) represent demyelinated areas.Abbreviations: EAE, experimental autoimmune encephalomyelitis; PSO, pomegranate seed oil; mAb, monoclonal antibody; H&E, hematoxylin and eosin; LFB, Luxol fast blue; PAS, periodic acid Schiff.
Mentions: To test if the lower clinical scores resulting from Nano-PSO treatment of EAE-induced mice are consistent with reduced appearance of EAE pathological markers, we looked in the brains of treated and untreated mice for several parameters, such as infiltration of immune cells, demyelination, and lipid oxidation. Figure 6 shows that while immune infiltrates can be detected in both treated and untreated EAE brains (sections E and G), Nano-PSO administration significantly reduced lipid oxidation levels (sections A and B and enlarged in D and F), as detected by the EO6 antibody staining in both treated and untreated brains. As opposed to EAE mice, no EO6 immunostaining (section C) or immune infiltrates (not shown) could be observed in naïve mice. Nano-PSO administration also reduced demyelination levels, as can be seen by comparing Luxol fast blue staining for myelin in both brains and spinal cords of untreated, EAE and naïve mice (section H–J). Interestingly, while the EO6 antibody recognized in the untreated mice both a diffuse and a light staining as well as focal points stained intensely (section D), the latter one reminiscent of the plaques in the patients with MS,6 in the Nano-PSO-treated EAE brains, only the light and diffuse pattern of immunostaining was apparent (section F). Quantification of the levels of EO6 stain was performed by measuring the positive area in six different fields at a magnification ×40. Stained pixels were measured using image pro analyzer 3D software, Media Cybernetics (“Materials and methods” section). The quantification results show that while for EAE-treated sections the percentage of positive area was 1.11±0.08, for the nontreated samples, it was 5.17±1.13 and for the wild-type brains 0.07±0.03.

Bottom Line: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress.Pathological examinations revealed that Nano-PSO administration dramatically reduced demyelination and oxidation of lipids in the brains of the affected animals, which are hallmarks of this severe neurological disease.On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.

ABSTRACT
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress. In this work, we administered a nanodroplet formulation of pomegranate seed oil (PSO), denominated Nano-PSO, to mice induced for experimental autoimmune encephalomyelitis (EAE), an established model of MS. PSO comprises high levels of punicic acid, a unique polyunsaturated fatty acid considered as one of the strongest natural antioxidants. We show here that while EAE-induced mice treated with natural PSO presented some reduction in disease burden, this beneficial effect increased significantly when EAE mice were treated with Nano-PSO of specific size nanodroplets at much lower concentrations of the oil. Pathological examinations revealed that Nano-PSO administration dramatically reduced demyelination and oxidation of lipids in the brains of the affected animals, which are hallmarks of this severe neurological disease. We propose that novel formulations of natural antioxidants such as Nano-PSO may be considered for the treatment of patients suffering from demyelinating diseases. On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration.

No MeSH data available.


Related in: MedlinePlus