Dataset Information

Selenium deficiency induces spleen pathological changes in pigs by decreasing selenoprotein expression, evoking oxidative stress, and activating inflammation and apoptosis.

ABSTRACT:

Background

The immune system is one aspect of health that is affected by dietary selenium (Se) levels and selenoprotein expression. Spleen is an important immune organ of the body, which is directly involved in cellular immunity. However, there are limited reports on Se levels and spleen health. Therefore, this study established a Se-deficient pig model to investigate the mechanism of Se deficiency-induced splenic pathogenesis.

Methods

Twenty-four pure line castrated male Yorkshire pigs (45 days old, 12.50 ± 1.32 kg, 12 full-sibling pairs) were divided into two equal groups and fed Se-deficient diet (0.007 mg Se/kg) or Se-adequate diet (0.3 mg Se/kg) for 16 weeks. At the end of the trial, blood and spleen were collected to assay for erythroid parameters, the osmotic fragility of erythrocytes, the spleen index, histology, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining, Se concentrations, the selenogenome, redox status, and signaling related inflammation and apoptosis.

Results

Dietary Se deficiency decreased the erythroid parameters and increased the number of osmotically fragile erythrocytes (P < 0.05). The spleen index did not change, but hematoxylin and eosin and TUNEL staining indicated that the white pulp decreased, the red pulp increased, and splenocyte apoptosis occurred in the Se deficient group. Se deficiency decreased the Se concentration and selenoprotein expression in the spleen (P < 0.05), blocked the glutathione and thioredoxin antioxidant systems, and led to redox imbalance. Se deficiency activated the NF-κB and HIF-1α transcription factors, thus increasing pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, and TNF-α), decreasing anti-inflammatory cytokines (IL-10, IL-13, and TGF-β) and increasing expression of the downstream genes COX-2 and iNOS (P < 0.05), which in turn induced inflammation. In addition, Se-deficiency induced apoptosis through the mitochondrial pathway, upregulated apoptotic genes (Caspase3, Caspase8, and Bak), and downregulated antiapoptotic genes (Bcl-2) (P < 0.05) at the mRNA level, thus verifying the results of TUNEL staining.

Conclusions

These results indicated that Se deficiency induces spleen injury through the regulation of selenoproteins, oxidative stress, inflammation and apoptosis.

SUBMITTER: Li S

PROVIDER: S-EPMC8127211 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundA declining selenium (Se) status constitutes a characteristic of critical illness and may affect disease course and survival. The dynamics of trauma-induced changes in biomarkers of Se status are poorly characterized, and an association with multiple organ failure (MOF) and mortality can be hypothesized. It was the aim of this study to investigate Se and selenoprotein P (SELENOP) concentrations in major trauma patients during the early posttraumatic period.Patients and methodsTwenty-four patients after major trauma (ISS ≥16) were included at our level one trauma center. Se supplementation ever during the 90-day observation period was defined as an exclusion criterion. Serum samples were drawn within less than 60 min after trauma, and after 6 h, 12 h, 24 h, 48 h, and 72 h. Serum Se was analyzed by X-ray fluorescence and SELENOP concentrations by ELISA. The data were correlated to clinical parameters, occurrence of MOF defined by MOF and APACHE II score, lung injury defined by Horowitz index and clinical outcome (90-days survival).ResultsSerum Se and SELENOP concentrations of the trauma patients were significantly below the average of healthy European subjects (mean ±SD; Se, 41.2±8.1 vs. 84.7±23.3 μg/L, P < 0.001; SePP, 1.5±0.3 vs. 4.3±1.0 mg/L, P < 0.001). A strong deficit was present already at the first time point (Se; 33.6±10.5 μg/L, SELENOP: 1.4±0.5 mg/L). The clinical scores collectively showed an inverse relation between health status and Se biomarkers. Patients who did not survive the 90-day observation period exhibited significantly lower initial post-trauma Se status than the surviving patients (mean±SD; Se, 24.7±7.2 vs. 39.2±8.4 μg/L, P<0.05; SePP, 1.1±0.4 vs. 1.6±0.4 mg/L, P<0.05).ConclusionVery low Se and SELENOP concentrations occur fast after major trauma and are associated with poor survival odds. These findings support the notion that early Se substitution may constitute a meaningful adjuvant treatment strategy in trauma patients.