Iron overload reduces synthesis and elimination of bile acids in rat liver

Prašnická, Alena; Lastuvkova, Hana; Faradonbeh, Fatemeh Alaei; Cermanova, Jolana; Hroch, Miloš; Mokrý, Jaroslav; Doleželová, Eva; Pávek, Petr; Zizalova, Katerina; Vı́tek, Libor; Nachtigal, Petr; Mičuda, Stanislav

doi:10.1038/s41598-019-46150-7

Cited by 18 publications

(10 citation statements)

References 33 publications

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“…injection of gleptoferron (iron-dextran heptonic acid complex), with concomitant down-regulation of the biliary bile acid transporter, BSEP. [34] Consistently, we also show that iron down-regulates BSEP, which may contribute to bile acid accumulation in serum and livers of IO mice.…”

Section: Discussionsupporting

confidence: 83%

Suppressed farnesoid X receptor by iron overload in mice and humans potentiates iron‐induced hepatotoxicity

et al. 2022

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Background and Aims: Iron overload (IO) is a frequent finding in the general population. As the major iron storage site, the liver is subject to iron toxicity. Farnesoid X receptor (FXR) regulates bile acid metabolism and is implicated in various liver diseases. We aimed to determine whether FXR plays a role in regulating iron hepatotoxicity. Approach and Results:Human and mouse hepatocytes were treated with ferric ammonium citrate or iron dextran (FeDx). Mice were orally administered ferrous sulfate or injected i.p. with FeDx. Wild-type and Fxr −/− mice were fed an iron-rich diet for 1 or 5 weeks. Mice fed an iron-rich diet were coadministered the FXR agonist, GW4064. Forced expression of FXR was carried out with recombinant adeno-associated virus 1 week before iron-rich diet feeding. Serum levels of bile acids and fibroblast growth factor 19 (FGF19) were quantified in adults with hyperferritinemia and children with β-thalassemia.The data demonstrated that iron suppressed FXR expression and signaling in human and mouse hepatocytes as well as in mouse liver and intestine.

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Section: Discussionsupporting

confidence: 83%

Suppressed farnesoid X receptor by iron overload in mice and humans potentiates iron‐induced hepatotoxicity

et al. 2022

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“…Excess iron has been shown to harm the liver and impair bile acid production (43). The relative abundance of B. wadsworthia in the intestines of mild β-thalassemia pregnant women reduced, which might be attributed to reduced bile acid production induced by iron overload.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Intestinal Flora in Pregnant Women with Mild Thalassemia Revealed by Metagenomics

Lun

Qiu

Zhao

et al. 2021

Jundishapur J Microbiol

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Background: At present, there is no report that the intestinal flora of pregnant women with mild thalassemia is different from that of healthy pregnant women. Objectives: This study compared the composition and changes of the intestinal flora of pregnant women with mild thalassemia to those of healthy pregnant women using metagenomic sequencing technology and evaluated the potential microecological risk for pregnant women and the fetus. Methods: The present study was carried out on 14 mild thalassemia pregnant women with similar backgrounds in the Affiliated Hospital of Putian University, Fujian, China. In the same period, 6 healthy pregnant women were selected as the control group. The genomic deoxyribonucleic acid was extracted from the sable stool samples of pregnant women. Illumina HiSeq sequencing technology was adopted after library preparation. Prodigal software (ver 2.6.3, Salmon software (ver 1.6.0, and Kraken software (ver 2) were used to analyze the sequence data. Moreover, analysis of variance and Duncan’s multiple-comparison test or Wilcoxon rank-sum test were used as statistical methods. Results: The characteristics of the intestinal flora of pregnant women with mild thalassemia differed significantly from those of healthy pregnant women, showing an increase in some conditionally pathogenic bacteria (e.g., Prevotella stercorea rose and Escherichia coli) and a decrease in some probiotic bacteria, which might affect pregnant women and cause physiological function damage to their offspring by changing metabolic pathways; however, further validation is needed. Conclusions: The diversity and composition of intestinal flora in pregnant women with mild thalassemia vary significantly from those in healthy pregnant women, especially at the genus and species levels, representing more profound alterations in intestinal microecology.

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“…We also observed the recurrence of gallstone crystallinity in the mouse gallbladder after receiving (Cys-nFeS)-S for 1 week. A similar observation was documented, showing that iron overload could result in the lipid peroxidation of mouse livers and increase the risk of gallstone formation. − This mechanism is like a double-edged sword that may be used to treat cholelithiasis or may have a negative effect similar to antibiotics. Therefore, these findings are important for the application of (Cys-nFeS)-S during treatment periods.…”

Section: Discussionmentioning

confidence: 60%

Oral Administration of Nanoiron Sulfide Supernatant for the Treatment of Gallbladder Stones with Chronic Cholecystitis

Ding

Jiang

Cheng

et al. 2020

ACS Appl. Bio Mater.

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Cholelithiasis with chronic cholecystitis is prevalent and threatens human health. Most cholecystitis caused by bacterial infection or biofilms is accompanied by gallstones in the clinic, making gallbladder removal the only effective solution. Here, we provide a strategy to eliminate gallstone biofilms and dissolve gallstones by oral administration of a supernatant derived from nanoscale iron sulfide (nFeS supernatant). First, by using gallstones obtained from the clinic, we simulated biofilm formation on gallstones and tested the antibacterial activity of a nFeS supernatant in vitro. We found that the supernatant kills bacteria with a 5-log reduction in viability and destroys the biofilm structure. Smashed gallstones coincubated with E. coli biofilms promote gallstone formation, while nFeS supernatant can inhibit this process. Second, by using a murine (C57BL/6) model of cholelithiasis and cholecystitis, we tested the antibacterial efficacy and therapeutic effects of nFeS supernatant on cholelithiasis in vivo. Animal experimental data show that oral administration of nFeS supernatant can reduce 60% of bacteria in the gallbladder and, remarkably, remove gallstones with 2 days of treatment compared with clinical drug combinations (chenodeoxycholid acid and ciprofloxacin). Third, by performing protein abundance analysis of L02 cells and mouse livers, we observed the changes in CYP7a1, HMGCR, and SCP2 expression, indicating that the nFeS supernatant can also regulate cholesterol metabolism to prevent gallstone formation. Finally, hematologic biochemistry analysis and high-throughput sequencing technology show that the nFeS supernatant possesses high biocompatibility. Therefore, our work demonstrates that the nFeS supernatant may be a potential regimen for the treatment of cholelithiasis and cholecystitis by oral administration.

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Iron overload reduces synthesis and elimination of bile acids in rat liver

Cited by 18 publications

References 33 publications

Suppressed farnesoid X receptor by iron overload in mice and humans potentiates iron‐induced hepatotoxicity

Suppressed farnesoid X receptor by iron overload in mice and humans potentiates iron‐induced hepatotoxicity

Characteristics of Intestinal Flora in Pregnant Women with Mild Thalassemia Revealed by Metagenomics

Oral Administration of Nanoiron Sulfide Supernatant for the Treatment of Gallbladder Stones with Chronic Cholecystitis

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