Gastric Helicobacter infection induces iron deficiency in the INS-GAS mouse

There is increasing evidence from clinical and population studies for a role of H. pylori infection in the aetiology of iron deficiency. Rodent models of Helicobacter infection are helpful for investigating any causal links and mechanisms of iron deficiency in the host. The aim of this study was to investigate the effects of gastric Helicobacter infection on iron deficiency and host iron metabolism/transport gene expression in hypergastrinemic INS-GAS mice. INS-GAS mice were infected with Helicobacter felis for 3, 6 and 9 months. At post mortem, blood was taken for assessment of iron status and gastric mucosa for pathology, immunohistology and analysis of gene expression. Chronic Helicobacter infection of INS- GAS mice resulted in decreased serum iron, transferrin saturation and hypoferritinemia and increased Total iron binding capacity (TIBC). Decreased serum iron concentrations were associated with a concomitant reduction in the number of parietal cells, strengthening the association between hypochlorhydria and gastric Helicobacter-induced iron deficiency. Infection with H. felis for nine months was associated with decreased gastric expression of iron metabolism regulators hepcidin, Bmp4 and Bmp6 but increased expression of Ferroportin 1, the iron efflux protein, iron absorption genes such as Divalent metal transporter 1, Transferrin receptor 1 and also Lcn2 a siderophore-binding protein. The INS-GAS mouse is therefore a useful model for studying Helicobacter-induced iron deficiency. Furthermore, the marked changes in expression of gastric iron transporters following Helicobacter infection may be relevant to the more rapid development of carcinogenesis in the Helicobacter infected INS-GAS model

Green Synthesized Silver Nanoparticles of Myrtus communis L (AgMC) Extract Inhibits Cancer Hallmarks via Targeting Aldose Reductase (AR) and Associated Signaling Network

In this current study, we demonstrated the green synthesis and characterization of silver nanoparticles using Myrtus communis L. plant extract (Ag-MC) and its evaluation of anticancer and antimicrobial activities. The green synthesis of (Ag-MC), was assessed by numerous characterization techniques such as ultraviolet-visible spectroscopy (UV-VIS), Fourier-transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD) transmission electron microscopy (TEM) and energy dispersive x-ray spectroscopy (EDX). The anti-cancer activity of the green synthesized silver nanoparticles was evaluated by the median inhibitory dose (IC50) on human liver carcinoma cell lines (HepG2). These results suggested that SN-NPs can be used as effective anticancer cell lines, as well as antibacterial and antiseptic agents in the medical field. This study showed that overexpression of aldose reductase (AR) in the human liver carcinoma cell line, HepG2, was down regulated by administration of SN-MC. The down regulation of AR was associated with abrogation of Pl3k/Akt, ERK and NF-kB pathways and the inhibition of cancer hallmarks, however, the target molecule for Ag-MC was not practically established. Thus it is still unknown if the consequences were due to AR inhibition or direct Ag-MC interaction with AR

Expression of iron binding and transport genes in murine gastric mucosa.

<p>Relative expression levels of genes involved in the binding and transport of iron were measured by qRT-PCR in tissue taken from the gastric corpus mucosa of INS-GAS mice at 9 months post-infection with <i>H. felis</i> and in age-matched uninfected INS-GAS mice and FVB/N controls. The graphs represent the mRNA abundance of the test genes relative to the house keeping gene, <i>Gapdh</i>. Uninfected (<b>white bars</b>) (n = 10) and <i>H. felis</i> infected (<b>hatched bars</b>) transgenic INS-GAS mice (n = 10) were compared to the uninfected FVB/N genetic background control (<b>solid bars</b>) (n = 5). The relative levels of Divalent Metal transporter 1 gene (<i>Dmt1</i>) (<b>A</b>), Transferrin receptor 1 (<i>Tfr1</i>) gene (<b>B</b>) and Lipocalin 2 (<i>Lcn2</i>) gene (<b>C</b>) were assessed. Error bars represent mean ± SEM. Statistical analysis by unpaired <i>t</i> test with Welch’s correction.</p

Real time PCR primers.

<p>Real time PCR primers.</p

Iron parameters in INS-GAS mice at 3, 6 and 9 months post-infection with <i>H. felis.</i>

<p>Box and whisker plots of serum iron (<b>A</b>), total iron binding capacity (TIBC) (<b>B</b>), transferrin saturation (<b>C</b>) and serum ferritin (<b>D</b>) in uninfected (<b>white boxes</b>) and <i>H. felis</i> infected (<b>hatched boxes</b>) INS-GAS mice. Time points as marked, group size n = 16−20, whiskers represent maximum/minimum values. Statistical analysis by unpaired <i>t</i> test with Welch’s correction.</p

Gastric histopathology in INS-GAS mice at 3,6 and 9 months post-infection with <i>H. felis</i>.

<p>Grade of gastric inflammation (<b>A</b>), corpus atrophy (<b>B</b>) and dysplasia (<b>C</b>) in uninfected control (<b>white bars</b>) and <i>H. felis</i> infected INS-GAS mice (<b>hatched bars</b>). Group size n = 5–7. Error bars represent mean ± SEM, when error present. Statistical analysis by the Mann Whitney U test.</p

Parietal cell number in INS-GAS mice at 3, 6 and 9 months post-infection with <i>H. felis.</i>

<p>Box and whisker plots of gastric parietal cell number in uninfected (<b>white boxes</b>) and <i>H. felis</i> infected (<b>hatched boxes</b>) INS-GAS mice. Group size n = 5−7 mice, whiskers represent maximum/minimum values. Statistical test is an unpaired <i>t</i> test with Welch’s correction.</p

Expression of iron metabolism regulation genes in murine gastric mucosa.

<p>Relative expression levels of genes involved in the regulation of iron metabolism were measured by qRT-PCR in biopsies of the gastric corpus mucosa of INS-GAS mice at 9 months post-infection with <i>H. felis</i> and in age-matched uninfected INS-GAS mice and FVB/N controls. The graphs represent the mRNA abundance of the test genes relative to the house keeping gene, <i>Gapdh</i>. Uninfected (<b>white bars</b>) (n = 10) and <i>H. felis</i> infected (<b>hatched bars</b>) transgenic INS-GAS mice (n = 10) were compared to the uninfected FVB/N genetic background control (<b>solid bars</b>) (n = 5). The relative levels of total hepcidin genes (<i>Hamp 1</i> and <i>2</i>) (<b>A</b>), Ferroportin 1 (<i>Fpn1</i>) gene (<b>B</b>), bone morphogenic protein gene 4 (<i>Bmp4</i>) (<b>C</b>) and 6 (<i>Bmp6</i>) gene (<b>D</b>) were assessed. Error bars represent mean ± SEM. Statistical analysis by unpaired <i>t</i> test with Welch’s correction.</p