Dataset Information

Effect of vitamin B12 supplementation on retinal lesions in diabetic rats.

ABSTRACT: Purpose:Diabetic retinopathy (DR) is the most common complication of diabetes involving microvasculature and neuronal alterations in the retina. Previously, we reported that vitamin B12 deficiency could be an independent risk factor for DR in humans. However, the effect of vitamin B12 supplementation in experimental DR is unknown. Thus, in this study, we investigated the impact of dietary supplementation of vitamin B12 on retinal changes in diabetic rats. Methods:Diabetes was induced in 2-month-old Sprague-Dawley rats and maintained for 4 months. One group of diabetic rats were fed normal levels of vitamin B12, and one group double the quantity of vitamin B12 (50 µg/kg diet). Vitamin B12 and homocysteine levels in the plasma were analyzed with radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC), respectively. At the end of 4 months of experimentation, the eyeballs were collected. Retinal changes were analyzed with hematoxylin and eosin (H&E) staining, immunoblotting, and immunofluorescence methods. Results:Dietary supplementation of vitamin B12 had no effect on food intake, bodyweight, fasting blood glucose, and plasma homocysteine levels in the diabetic rats. However, vitamin B12 supplementation prevented loss of rhodopsin, and overexpression of VEGF, and completely prevented overexpression of HIF1?, GFAP, and endoplasmic reticulum (ER) stress markers (GRP78, ATF6?, XBP1, CHOP, and caspase 12) in the diabetic rat retina. Further, vitamin B12 ameliorated apoptosis in the retina as shown with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and prevented retinal thinning. Conclusions:Vitamin B12 supplementation of diabetic rats appeared to be beneficial by circumventing retinal hypoxia, VEGF overexpression, and ER stress-mediated cell death in the retina. The present study adds another potential therapeutic strategy of vitamin B12 in diabetes.

SUBMITTER: Reddy SS

PROVIDER: S-EPMC7190579 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of vitamin B<sub>12</sub> supplementation on retinal lesions in diabetic rats.

Reddy S Sreenivasa SS Prabhakar Y K YK Kumar Ch Uday CU Reddy P Yadagiri PY Reddy G Bhanuprakash GB

Molecular vision 20200424

<h4>Purpose</h4>Diabetic retinopathy (DR) is the most common complication of diabetes involving microvasculature and neuronal alterations in the retina. Previously, we reported that vitamin B<sub>12</sub> deficiency could be an independent risk factor for DR in humans. However, the effect of vitamin B<sub>12</sub> supplementation in experimental DR is unknown. Thus, in this study, we investigated the impact of dietary supplementation of vitamin B<sub>12</sub> on retinal changes in diabetic rats. ...[more]

PMID: 32355441

Similar Datasets

Project description:In order to understand the molecular mechanism responsible for the therapeutic potential of vitamin D, we conducted an analysis of the liver transcriptome – a central place of metabolic changes. The experiment was carried out on adult female rats (about one year old), n=18, divided into three experimental subjects, receiving different doses of vitamin D for three months: group I - 0, group II - 1000 U/Kg, group III - 5000 U/Kg. After the experiment, the biochemical and haematological parameters of the blood were evaluated. RNA-seq was used to analyze the changes in the liver transcriptome, and Gene Set Enrichment Analysis (GSEA) was used to identify enrichments in gene expression profiles of experimental groups. qPCR was employed to evaluate the expression of several genes connected to cholesterol biosynthesis, metallothioneins, vitamin D metabolism and others. At the end of the experiment, 25(OH) vitamin D concentrations were as follows: group I: 29 ng/ml, group II 43: ng/ml, group III: 70 ng/mL. Considering blood parameters, we observed a lower platelet count (p<0,008) and significantly higher (p<0.02) number of WBC in rats supplemented with 1000 U/Kg than in rats from group III (5000 U/Kg), but no difference between rats from group I and III were detected in these parameters. Moreover, we noted a trend (p<0.06 ) in total cholesterol concentration, suggesting a linear decrease with increasing doses of vitamin D. RNA-seq analysis did not identify any differentially expressed genes with FDR<0.05 in any of the three comparisons. However, GSEA revealed significant activation of the number of processes and pathways. In the I vs III comparison, the most enriched were the genes from the “metallothionein, and TspO/MBR family” (Enrichment Score=8,170, FDR= 0.00006), the genes associated with “glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity” (Enrichment Score=5.13, FDR<00049) and the genes associated with “Negative regulation of tumour necrosis factor production” (Enrichment score=1.26, FDR0.0064. qPCR analysis identified significant upregulation of Mt1, Mt2 and Orm1 genes in animals receiving high doses of vitamin D (p<0.025, p<0.025, p<0009, respectively). Moreover, significant downregulation of Srebp2 and Insig2 was observed in both experimental groups when compared to the control group (p<0.003, p<0.036, respectively). Our results support the potential of vitamin D supplementation in ameliorating oxidative stress, inflammation and high blood cholesterol and underlie the need for further studies aimed at identifying optimal vitamin D doses with therapeutic effects.

Project description:To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/day for one year in patients with diabetic neuropathy (DN). In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score). B12 levels increased from 232.0 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up, p < 0.0001, in the active group but not in the control group. VPT, MNSIQ, QoL, pain score, SNCV, SNAP, and ESCF significantly improved in the active group (p < 0.001, p = 0.002, p < 0.0001, p < 0.000, p < 0.0001, p < 0.0001, and p = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (p = 0.025, p = 0.017, p = 0.045, p < 0.0001, and p < 0.0001, respectively). The treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE.

Project description:More effective treatments are needed for negative symptoms of schizophrenia, which are typically chronic, disabling, and costly. Negative symptoms have previously been associated with reduced blood folate levels, especially among patients with low-functioning variants in genes that regulate folate metabolism, suggesting the potential utility of folate supplementation.To determine whether folic acid plus vitamin B12 supplementation reduces negative symptoms of schizophrenia and whether functional variants in folate-related genes influence treatment response.Parallel-group, randomized, double-blind, placebo-controlled clinical trial of 16 weeks of treatment with 2 mg of folic acid and 400 ?g of vitamin B12.Three community mental health centers affiliated with academic medical centers in the United States.Outpatients with chronic schizophrenia who were psychiatrically stable but displayed persistent symptoms despite antipsychotic treatment. Eligible patients were 18 to 68 years old, were treated with an antipsychotic agent for 6 months or more at a stable dose for 6 weeks or more, and scored 60 or more on the Positive and Negative Syndrome Scale.One hundred forty subjects were randomized to receive daily oral folic acid plus vitamin B12 or placebo.Change in negative symptoms (Scale for the Assessment of Negative Symptoms [SANS]), as well as positive and total symptoms (Positive and Negative Syndrome Scale).Folate plus vitamin B12 improved negative symptoms significantly compared with placebo (group difference, -0.33 change in SANS score per week; 95% CI, -0.62 to -0.05) when genotype was taken into account but not when genotype was excluded. An interaction of the 484C>T variant of FOLH1 (rs202676) with treatment was observed (P = .02), where only patients homozygous for the 484T allele demonstrated significantly greater benefit with active treatment (-0.59 change in SANS score per week; 95% CI, -0.99 to -0.18). In parallel, we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load (P = .03), which persisted until 8 weeks of treatment. Change in positive and total symptoms did not differ between treatment groups.Folate plus vitamin B12 supplementation can improve negative symptoms of schizophrenia, but treatment response is influenced by genetic variation in folate absorption. These findings support a personalized medicine approach for the treatment of negative symptoms.clinicaltrials.gov Identifier: NCT00611806.

Dataset Information

Effect of vitamin B12 supplementation on retinal lesions in diabetic rats.

Publications

Effect of vitamin B<sub>12</sub> supplementation on retinal lesions in diabetic rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets