Vitamin D-An Effective Antioxidant in an Animal Model of Progressive Multiple Sclerosis

被引:6
作者
Haindl, Michaela Tanja [1 ]
Ucal, Muammer [2 ]
Wonisch, Willibald [3 ]
Lang, Michaela [1 ,4 ]
Nowakowska, Marta [2 ]
Adzemovic, Milena Z. Z. [5 ]
Khalil, Michael [1 ]
Enzinger, Christian [1 ]
Hochmeister, Sonja [1 ]
机构
[1] Med Univ Graz, Dept Neurol, A-8036 Graz, Austria
[2] Med Univ Graz, Dept Neurosurg, A-8036 Graz, Austria
[3] Med Univ Graz, Otto Loewi Res Ctr, Dept Physiol Med, A-8010 Graz, Austria
[4] Univ Appl Sci Wiener Neustadt, Fac Hlth, Campus 1, A-2700 Wiener Neustadt, Austria
[5] Karolinska Inst, Dept Clin Neurosci, S-17164 Stockholm, Sweden
关键词
vitamin D; progressive multiple sclerosis; animal model; neuroprotection; OXIDATIVE STRESS; CELLS;
D O I
10.3390/nu15153309
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Vitamin D (VD) is the most discussed antioxidant supplement for multiple sclerosis (MS) patients and many studies suggest correlations between a low VD serum level and onset and progression of the disease. While many studies in animals as well as clinical studies focused on the role of VD in the relapsing-remitting MS, knowledge is rather sparse for the progressive phase of the disease and the development of cortical pathology. In this study, we used our established rat model of cortical inflammatory demyelination, resembling features seen in late progressive MS, to address the question about whether VD could have positive effects on reducing cortical pathology, oxidative stress, and neurofilament light chain (NfL) serum levels. For this purpose, we used male Dark Agouti (DA) rats, with one group being supplemented with VD (400 IE per week; VD+) from the weaning on at age three weeks; the other group received standard rodent food. The rat brains were assessed using immunohistochemical markers against demyelination, microglial activation, apoptosis, neurons, neurofilament, and reactive astrocytes. To evaluate the effect of VD on oxidative stress and the antioxidant capacity, we used two different oxidized lipid markers (anti- Cu++ and HOCl oxidized LDL antibodies) along with colorimetric methods for protective polyphenols (PP) and total antioxidative capacity (TAC). NfL serum levels of VD+ and VD- animals were analyzed by fourth generation single-molecule array (SIMOA) analysis. We found significant differences between the VD+ and VD- animals both in histopathology as well as in all serum markers. Myelin loss and microglial activation is lower in VD+ animals and the number of apoptotic cells is significantly reduced with a higher neuronal survival. VD+ animals show significantly lower NfL serum levels, a higher TAC, and more PP. Additionally, there is a significant reduction of oxidized lipid markers in animals under VD supplementation. Our data thus show a positive effect of VD on cellular features of cortical pathology in our animal model, presumably due to protection against reactive oxygen species. In this study, VD enhanced remyelination and prevented neuroaxonal and oxidative damage, such as demyelination and neurodegeneration. However, more studies on VD dose relations are required to establish an optimal response while avoiding overdosing.
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页数:14
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