Vitamin D3 increases the Caspase-3 p12, MTHFR, and P-glycoprotein reducing amyloid-β42 in the kidney of a mouse model for Down syndrome

• DOI: 10.1016/j.lfs.2019.06.012
• Publication Date: 2019-06-06T15:42:57Z
• Authors: Fabiana de Campos...; João Simão de Mel...; Merari de Fátima ...; Carla Patrícia Ca...; Eny Maria Goloni-...; Érika Cristina Pa...
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Amyloid beta-Peptides; Caspase 3; Kidney; Peptide Fragments; 3. Good health; Amyloid beta-Protein Precursor; Disease Models, Animal; Mice; 03 medical and health sciences; Dietary Supplements; Animals; Female; ATP Binding Cassette Transporter, Subfamily B, Member 1; Down Syndrome; Methylenetetrahydrofolate Reductase (NADPH2); Cholecalciferol

Renal dysfunction has been reported in individuals with Down syndrome (DS); however, the causes and mechanisms involved remain unknown. Here, we present a proposal for how the triplication of the amyloid beta precursor protein (APP) and, mainly the amyloid β peptide 1-42 (Aβ42) can favor the development of renal abnormalities in DS. We evaluated the effects of vitamin D3 (VD3) supplementation on morphofunctional aspects and the repercussions on the presence and localization of Aβ42, methylenetetrahydrofolate reductase (MTHFR), caspase-3 p12, and P-glycoprotein (Pgp) in the renal tissue of DS mouse model.Twenty female mice (14-week-old) belonging to the B6EiC3Sn-Rb(12.Ts171665Dn)2Cje/CjeDnJ lineage were divided into four experimental groups (n = 5/group): common diet; trisomy (Ts) and wild-type (Wt); and high doses VD3, Ts(VD3), and Wt(VD3). All the groups were treated for 10 weeks. At 24 weeks, the protocol experimental was interrupted. The kidney was weighed, collected, and processed for immunochemical analysis for Aβ42, Caspase-3 p12, MTHFR, and Pgp proteins. All data were analyzed statistically.Our results showed that VD3 promoted an increase in caspase-3 p12, MTHFR, and Pgp, and consequently contributed to reduced Aβ42 in the renal tissue of a mouse model of DS. Furthermore, VD3 treatment affected the plasma creatinine and urea levels and contributed to the attenuation of the dilation of Bowman's space observed in trisomic mice.Finally, the results showed that VD3 may activate specific mechanisms involved in reduced Aβ42 and tissue repair in the kidneys of a mouse model for Down syndrome.