Association between Nfr2, HO-1, NF-kB Expression, Plasma ADMA, and Oxidative Stress in Metabolic Syndrome.

Endothelial dysfunction is one of the major factors in the pathogenesis of metabolic syndrome (MetS), and its molecular mechanisms are not completely understood. The present study aimed to examine the connection between nuclear factor2-related factor2 (Nrf2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), heme oxygenase 1 (HO-1), and plasma asymmetric dimethylarginine (ADMA) and malondialdehyde (MDA) in people with MetS. Participants in the study were as follows: with MetS (n = 30) and without MetS (Control) (n = 14). Expression of Nrf2, NF-kB, and HO-1 was measured in peripheral blood mononuclear cells (PBMCs). Plasma ADMA was determined using the ELISA technique and MDA via the thiobarbituric acid method. Our study showed that mRNA of NF-kB, Nrf2, and HO-1 levels in PBMCs in the MetS group were significantly higher than in the controls by 53%, 130%, and 185% (p < 0.05), respectively. Similarly, elevated levels of MDA (by 78%, p < 0.001) and ADMA (by 18.7%, p < 0.001) were established in the MetS group. Our findings show the importance of transcription factor Nrf2, playing an integral role in the protection of the endothelium, and of NF-κB, a transcription factor mediating the inflammatory response in MetS. Knowledge of complex cellular-molecular mechanisms would allow the use of biomarkers such as Nrf2, NF-kB, HO-1, and ADMA for the assessment of endothelial dysfunction in clinical practice.

Effect of vitamin D metabolites and gene expression of vitamin D receptor, and 1-alpha-hydroxylase related to the sperm quality.

The incidence of male fertility disorders has increased greatly due to various genetic and lifestyle factors. Recently, it has been hypothesized that vitamin D may be involved with idiopathic infertility. The goal of the study was to determine the effect and relationship between blood vitamin D metabolites, intracellular sperm vitamin D levels, and gene expression of 1-α-hydroxylase and VDR, with regard to semen quality. Seventy volunteers aged 25-45 were involved in the study. According to spermogram analysis, participants were stratified into normozoospermic control group, non-normozoospermic target group, and oligoasthenoteratozoospermic group. Vitamin D metabolites (total 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol) in blood and spermatozoa were determined by ELISA. Free and bioavailable 25-hydroxycholecalciferol were calculated using the Vermeulen equation. mRNA expression of VDR and 1-α hydroxylase was evaluated by qPCR. Free and bioavailable 25-hydroxycholecalciferol were significantly higher in the control group compared to the target group and compared to the oligoasthenoteratozoospermic group . Intracellular sperm 1,25-dihydroxycholecalciferol was higher in the control group compared to the target group. The mRNA levels of 1- α-hydroxylase were significantly higher in the control samples, while VDR expression was significantly higher in the target group. Significant positive correlations were established between free and bioavailable 25-hydroxycholecalciferol with sperm motility and morphology. Vitamin D metabolites in blood and intracellular sperm 1,25-dihydroxycholecalciferol seem to exert beneficial effects on sperm motility and morphology. Regarding sperm quality, these effects are more pronounced in the free and bioavailable 25OHD compared to the total 25OHD in blood. Higher expression of 1-α-hydroxylase likely leads to higher intracellular levels of 1,25-dihydroxycholecalciferol, which could contribute to sperm motility and morphology. Higher VDR expression may be a compensatory mechanism related to lower intracellular sperm 1,25-dihydroxycholecalciferol.