scholarly journals Vitamin B12 and folic acid alleviate symptoms of nutritional deficiency by antagonizing aryl hydrocarbon receptor

2020 ◽  
Vol 117 (27) ◽  
pp. 15837-15845 ◽  
Author(s):  
Daniel J. Kim ◽  
Arvind Venkataraman ◽  
Priyanka Caroline Jain ◽  
Eleanor P. Wiesler ◽  
Melody DeBlasio ◽  
...  

Despite broad appreciation of their clinical utility, it has been unclear how vitamin B12 and folic acid (FA) function at the molecular level to directly prevent their hallmark symptoms of deficiency like anemia or birth defects. To this point, B12 and FA have largely been studied as cofactors for enzymes in the one-carbon (1C) cycle in facilitating the de novo generation of nucleotides and methylation of DNA and protein. Here, we report that B12 and FA function as natural antagonists of aryl hydrocarbon receptor (AhR). Our studies indicate that B12 and FA bind AhR directly as competitive antagonists, blocking AhR nuclear localization, XRE binding, and target gene induction mediated by AhR agonists like 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and 6-formylindolo[3,2-b]carbazole (FICZ). In mice, TCDD treatment replicated many of the hallmark symptoms of B12/FA deficiency and cotreatment with aryl hydrocarbon portions of B12/FA rescued mice from these toxic effects. Moreover, we found that B12/FA deficiency in mice induces AhR transcriptional activity and accumulation of erythroid progenitors and that it may do so in an AhR-dependent fashion. Consistent with these results, we observed that human cancer samples with deficient B12/FA uptake demonstrated higher transcription of AhR target genes and lower transcription of pathways implicated in birth defects. In contrast, there was no significant difference observed between samples with mutated and intact 1C cycle proteins. Thus, we propose a model in which B12 and FA blunt the effect of natural AhR agonists at baseline to prevent the symptoms that arise with AhR overactivation.

2018 ◽  
Vol 19 (12) ◽  
pp. 3762 ◽  
Author(s):  
Anaïs Wakx ◽  
Margaux Nedder ◽  
Céline Tomkiewicz-Raulet ◽  
Jessica Dalmasso ◽  
Audrey Chissey ◽  
...  

The human placenta is an organ between the blood of the mother and the fetus, which is essential for fetal development. It also plays a role as a selective barrier against environmental pollutants that may bypass epithelial barriers and reach the placenta, with implications for the outcome of pregnancy. The aryl hydrocarbon receptor (AhR) is one of the most important environmental-sensor transcription factors and mediates the metabolism of a wide variety of xenobiotics. Nevertheless, the identification of dietary and endogenous ligands of AhR suggest that it may also fulfil physiological functions with which pollutants may interfere. Placental AhR expression and activity is largely unknown. We established the cartography of AhR expression at transcript and protein levels, its cellular distribution, and its transcriptional activity toward the expression of its main target genes. We studied the profile of AhR expression and activity during different pregnancy periods, during trophoblasts differentiation in vitro, and in a trophoblast cell line. Using diverse methods, such as cell fractionation and immunofluorescence microscopy, we found a constitutive nuclear localization of AhR in every placental model, in the absence of any voluntarily-added exogenous activator. Our data suggest an intrinsic activation of AhR due to the presence of endogenous placental ligands.


2021 ◽  
Vol 9 (2) ◽  
Author(s):  
Uni Gamayani ◽  
Titin Junaidi ◽  
Nushrotul Lailiyya ◽  
Nur Suryawan ◽  
Nanan Sekarwana

Vitamin B9 (folic acid) and B12 (cobalamin) are essential vitamins that play roles in the process of hematopoiesis and maintaining the function of peripheral nerves. Therefore, these deficiencies may create a risk for peripheral neuropathy in beta-thalassemia major patients. The purpose of this study is to determine the relationship between vitamin B9 level, vitamin B12 level, and peripheral neuropathy in beta-thalassemia major children. It was an observational analytical study with a case-control design has been conducted at Dr. Hasan Sadikin General Hospital Bandung, Indonesia, in May–July 2019. There were 47 beta-thalassemia major children with peripheral neuropathy (case) and 41 healthy children (control). All subjects completed a general demographic questionnaire, underwent neurological examination, and were tested for vitamin B9 and B12 serum levels. Data were then analyzed using the unpaired t test to compare the vitamin levels between both groups and Spearman’s rank correlation test to investigate the correlation between vitamin levels and the number of affected nerves in the case group. Comparison of folic acid levels in the case group (21.52±6.22 ng/mL) and the control group (23.81±7.51 ng/mL) showed no significant difference (p=0.19). In contrast, cobalamin in the case group (288.57±168.61 ng/mL) and the control group (385.95±197.48 ng/mL) showed a significant difference (p=0.01). In addition, there was a moderate correlation (p=0.004, r=0.41) between folic acid level and the number of motoric nerves affected in the case group. In conclusion, cobalamin level correlates with peripheral neuropathy in beta-thalassemia major patients, and folic acid level correlates with the number of affected nerves, especially motoric nerves. HUBUNGAN ANTARA VITAMIN B9 (ASAM FOLAT), VITAMIN B12 (KOBALAMIN), DAN NEUROPATI PERIFER PADA ANAK DENGAN TALASEMIA BETA MAYORVitamin B9 (asam folat) dan B12 (kobalamin) merupakan vitamin esensial yang berperan dalam proses hematopoiesis dan menjaga fungsi saraf tepi. Defisiensi vitamin ini dapat menimbulkan risiko neuropati perifer pada pasien talasemia beta mayor. Tujuan penelitian ini mengetahui hubungan antara kadar vitamin B9, vitamin B12, dan neuropati perifer pada anak talasemia beta mayor. Metode penelitian ini adalah analitik observasional dengan rancangan studi kasus kontrol yang dilakukan di RSUP Dr. Hasan Sadikin Bandung, Indonesia pada Mei–Juli 2019. Terdapat 47 anak talasemia beta mayor dengan neuropati perifer (kelompok kasus) dan 41 anak sehat (kelompok kontrol). Seluruh subjek penelitian mengisi kuesioner demografi umum, menjalani pemeriksaan fisis neurologis, serta dilakukan tes kadar vitamin B9 dan B12 serum. Uji t test tidak berpasangan digunakan untuk membandingkan kadar vitamin pada kedua kelompok dan uji korelasi Spearman untuk membandingkan kadar kedua vitamin tersebut dengan jumlah saraf yang terkena pada kelompok kasus. Perbandingan kadar asam folat kelompok kasus (21,52±6,22 ng/mL) dan kelompok kontrol (23,81±7,51 ng/mL) menunjukkan perbedaan yang tidak bermakna (p=0,19), sedangkan perbandingan kadar kobalamin kelompok kasus (288,57±168,61 ng/mL) dan kelompok kontrol (385,95±197,48 ng/mL) menunjukkan perbedaan yang bermakna (p=0,01). Selain itu, terdapat korelasi sedang (p=0,004; r=0,41) antara kadar asam folat dam jumlah saraf motorik yang terkena pada kelompok kasus. Kesimpulan, kadar kobalamin berhubungan dengan neuropati perifer pada penderita talasemia beta mayor dan kadar asam folat berhubungan dengan jumlah saraf yang terkena, terutama saraf motorik.


2020 ◽  
Author(s):  
Mchiko Ishii ◽  
Yukimoto Ishii ◽  
Tomohisa Nakayama ◽  
Yasuo Takahashi ◽  
Satoshi Asai

Abstract Aim: We investigated the relationship between trimethyl-13C-caffeine breath test (triCBT) and single nucleotide polymorphisms (SNPs) that are related to caffeine metabolism and consumption.Methods: Subjects were 132 young healthy adults (median 21 years: 101 male, 31 female). Subjects completed a questionnaire that enquired about their smoking status, consumption of caffeinated drinks (including coffee, black tea, green tea), height, weight, and body mass index (BMI). DNA was extracted from saliva, and genotyping was performed using TaqMan® SNP Genotyping for cytochrome P4501A2 rs762551, rs2472297, and aryl-hydrocarbon receptor rs4410790. Trimethyl 13C-caffeine (100 mg) was dissolved in distilled water and administered orally. Subsequently, breath samples were collected every 10 mins for 90 mins. Infrared spectroscopy was used to analyze the amount of 13CO2 in the expired breath, and the sum (Δ13CO2) over 90 min (S90m) was calculated.Results: All subjects had genotype CC for rs2472297. S90m was not significantly different among rs762551 genotypes; however, there was a significant difference in S90m among rs4410790 genotypes. Δ13CO2 was significantly affected by rs4410790 SNPs and smoking. The receiver operating characteristic area under the curve was 0.758 when rs4410790 phenotype C was considered positive. When the cutoff value was set to S90m (23.4 ‰), the sensitivity and specificity were 71.4% and 72.1%, respectively.Conclusions: Our results suggest that caffeine demethylation is affected by rs4410790 SNPs and smoking, and that triCBT can be used to identify SNPs in rs4410790.


2019 ◽  
Vol 44 (5) ◽  
pp. 661-666
Author(s):  
Dilber Çoban Ramazan ◽  
Ülker Anadol ◽  
A. Destina Yalçın ◽  
A. Süha Yalçın

Abstract Objective Homocysteine is a sulfur containing amino acid that is formed during methionine metabolism. Patients under long-term antiepileptic drug treatment often have hyperhomocysteinemia. These patients have low levels of serum folate, vitamin B12 and vitamin B6, all of which are associated with homocysteine metabolism. We have investigated the effects of valproic acid and new generation antiepileptic drugs (lamotrigine and levetiracetam) on plasma levels of homocysteine and aminothiols as well as serum vitamin B12 and folic acid. Materials and methods Forty-seven idiopathic epileptic patients on antiepileptic drugs were compared with 38 age-matched healthy controls. Commercial immunoassay methods were used for vitamin B12 and folic acid analyses. Homocysteine, cysteine, cysteinylglycine and glutathione levels were determined by high performance liquid chromatography. Results There was no significant difference in patient and control values in terms of vitamin B12, folic acid and homocysteine. Valproic acid and lamotrigine seemed to effect aminothiol redox status. Glutathione levels of epileptic patients receiving valproic acid and lamotrigine were higher than controls. Conclusion Our results suggest that redox homeostasis may be impaired and glutathione synthesis increased in response to the oxidative stress caused by antiepileptic drug use.


2007 ◽  
Vol 73 (3) ◽  
pp. 769-777 ◽  
Author(s):  
Patricia Monteiro ◽  
David Gilot ◽  
Eric Le Ferrec ◽  
Claudine Rauch ◽  
Dominique Lagadic-Gossmann ◽  
...  

Gene ◽  
2013 ◽  
Vol 513 (1) ◽  
pp. 225-230 ◽  
Author(s):  
Chengzhang Luo ◽  
Peng Zou ◽  
Guixiang Ji ◽  
Aihua Gu ◽  
Peng Zhao ◽  
...  

2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Dwi Retna Prihati ◽  
Gita Kostania

Abstract: MMN, Newborn Baby Weight. During pregnancy food is required with good quality and quantity to meet the nutritional needs of mother and baby. The low nutritional status of pregnant women during pregnancy can lead to various adverse effects for mothers and infants, such as those born with Low Birth Weight (LBW). LBW babies have a 10 to 20 times greater chance of dying than babies born with enough birth weight. Multiple Micro Nutrient (MMN) contains 15 types of vitamins and minerals most important for pregnant women, including vitamin A, vitamin E, vitamin D, vitamin B1, vitamin B2, niacin, Vitamin B6, vitamin B12, folic acid, vitamin C, Fe , folic acid, Zink, Copper, Selenium, and Iodine. MMN is one of the nutrients to prevent the occurrence of anemia because in MMN there are factors forming Hemoglobin ie Fe, Vitamin B12 and folic acid. The availability of adequate hemoglobin makes the metabolic system work well. Lack of hemoglobin not only affects the health of the mother but also affects the health of the fetus it contains, including the growth of the fetal inhibition (such as weight, body length). The purpose of this study was to prove the effect of MMN on newborn weight in Pandes Klaten village. This type of research is arestrospective study with cross sectional design. The subjects of this study were BBL (newborn) whose mother consumed MMN during pregnancy. Different test sing Independent T-test to compare control group and treatment group. Significant value in this study was p <0.05. The results of this study were no significant difference between birth weight between control group and MMN treatment group (P = 0.879). In conclusion MMN has no significant effect on newborn weight gain.


Author(s):  
Feridun Gurlek ◽  
Eyyüp Taşdemir

Background: Etiopathogenesis in Chronic Spontaneous Urticaria (CSU) is not completely clear. Some vitamins, inflammatory markers and even some microorganisms have been held responsible for this process. There are limited number of publications in this field in the literature. The aim of this study is to shed light on the etiology of chronic urticaria.Methods: This study included a total of 90 patients that 45 with CSU patients and 45 healthy subjects who admitted to Allergy and Clinical Immunology and Internal Medicine outpatient clinics of University of Health Sciences, Bursa Postgraduate Research and Training Hospital between October 2018 and June 2019. They were between the ages of 18-55. Both groups were examined for CRP, Procalcitonin (PCT), Erythrocyte Sedimentation Rate (ESR), Vitamin B12, vitamin D, folic acid and Helicobacter pylori (H. pylori) antibody.Results: ESR, CRP, PCT, Vitamin B12 and Vitamin D levels were not statistically different according to the groups (p>0.05). Folic acid levels were significantly different between groups (p=0.026; p<0.05); the low folic acid ratio in the healthy group is higher than in the urticaria group. There was no statistically significant difference between the groups according to H. pylori antibody positivity (p>0.05). In urticaria group, sufficient vitamin D ratio was higher in who were H. pylori antibody negative. In healthy group; insufficient and sufficient vitamin D ratio was higher in who were H. pylori antibody positive.Conclusions: There is no direct correlation between urticaria and Vitamin B12, Vitamin D, folic acid deficiencies and inflammatory biomarkers. CRP, ESR and PCT levels may be generally normal as in patients with urticaria. However, CRP may also increase slightly in patients with severe urticaria. It may be wrong to see H. pylori as a direct cause of urticaria.


2020 ◽  
Author(s):  
Karolína Poulíková ◽  
Iveta Zůvalová ◽  
Barbora Vyhlídalová ◽  
Kristýna Krasulová ◽  
Eva Jiskrová ◽  
...  

ABSTRACTCarvones, the constituents of essential oils of dill, caraway, and spearmint, were reported to antagonize the human aryl hydrocarbon receptor (AhR); however, the exact molecular mechanism remains elusive. We show that carvones are non-competitive allosteric antagonists of the AhR that inhibit the induction of AhR target genes in a ligand-selective and cell type-specific manner. Carvones do not displace radiolabeled ligand from binding at the AhR, but they bind allosterically within the bHLH/PAS-A region of the AhR. Carvones did not influence a translocation of ligand-activated AhR into the nucleus. Carvones inhibited the heterodimerization of the AhR with its canonical partner ARNT and subsequent binding of the AhR to the promotor of CYP1A1. Interaction of carvones with potential off-targets, including ARNT and protein kinases, was refuted. This is the first report of a small dietary monoterpenoids as a new class of AhR non-competitive allosteric antagonists with the potential preventive and therapeutic application.


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