Alteration of the enterohepatic recirculation of bile acids in rats after exposure to ionizing radiation

Scanff, P.; Souidi, Maâmar; Grison, Stéphane; Griffiths, N. M.; Gourmelon, P.

doi:10.1139/y03-131

Cited by 6 publications

(7 citation statements)

References 43 publications

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“…Problems such as anorexia, weight loss 47) and visceral tissue damage were not found, although they have been described with stronger external gamma irradiation. 48) Also, our study did not show a body weight increase as described in case of higher cumulated irradiation (6 Gy) at low-dose rate in rodents exposed during the same duration (9 months).…”

Section: Discussionmentioning

confidence: 92%

The Metabolomic Approach Identifies a Biological Signature of Low-dose Chronic Exposure to Cesium 137

Grison¹,

Martin²,

Grandcolas³

et al. 2012

JRR

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Reports have described apparent biological effects of (137)Cs (the most persistent dispersed radionuclide) irradiation in people living in Chernobyl-contaminated territory. The sensitive analytical technology described here should now help assess the relation of this contamination to the observed effects. A rat model chronically exposed to (137)Cs through drinking water was developed to identify biomarkers of radiation-induced metabolic disorders, and the biological impact was evaluated by a metabolomic approach that allowed us to detect several hundred metabolites in biofluids and assess their association with disease states. After collection of plasma and urine from contaminated and non-contaminated rats at the end of the 9-months contamination period, analysis with a LC-MS system detected 742 features in urine and 1309 in plasma. Biostatistical discriminant analysis extracted a subset of 26 metabolite signals (2 urinary, 4 plasma non-polar, and 19 plasma polar metabolites) that in combination were able to predict from 68 up to 94% of the contaminated rats, depending on the prediction method used, with a misclassification rate as low as 5.3%. The difference in this metabolic score between the contaminated and non-contaminated rats was highly significant (P = 0.019 after ANOVA cross-validation). In conclusion, our proof-of-principle study demonstrated for the first time the usefulness of a metabolomic approach for addressing biological effects of chronic low-dose contamination. We can conclude that a metabolomic signature discriminated (137)Cs-contaminated from control animals in our model. Further validation is nevertheless required together with full annotation of the metabolic indicators.

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Section: Discussionmentioning

confidence: 92%

The Metabolomic Approach Identifies a Biological Signature of Low-dose Chronic Exposure to Cesium 137

Grison¹,

Martin²,

Grandcolas³

et al. 2012

JRR

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“…Previously reported studies have shown that radiation causes bile salt malabsorption in the intestine due to terminal ileal damage (6, 7). The metabolomics results above also indicated altered levels of bile acids in feces after irradiation.…”

Section: Resultsmentioning

confidence: 99%

“…This is in accordance with a previously reported study in rats showing an increase in conjugated bile acids postirradiation as the result of reduced capacity of the microbiome to deconjugate and desulphate bile acids (29). In addition, a separate study concluded that bile acid levels increased as early as 24 h postirradiation and remained persistently high three days after exposure (7). Under physiological conditions, 90% of bile acids are reabsorbed by the gut by the highly efficient enterohepatic recirculation system (38), which may indicate that the radiation-induced bile acid increases in the colonic contents is due to the reduction of intestinal absorption caused by radiation.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, cytotoxic effects of radiation exposure can also lead to defects in the intestinal epithelial barrier, which offers higher permeability to luminal bacteria and triggers immune responses (5). Furthermore, while the severity of these histological changes tends to be dose dependent (4), there are also secondary adverse GI effects that are directly related to the radiation exposure such as bile salt malabsorption from terminal ileal damage (6, 7), malabsorption of lactose or other fermentable sugars (8), small bowel bacterial overgrowth (9, 10) and altered transit time (11). Therefore, to study the local biology and the perturbations in gut homeostasis, stool may be a valuable biofluid.…”

Section: Introductionmentioning

confidence: 99%

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An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host-Microbiome Axis

Goudarzi¹,

Mak

Jacobs

et al. 2016

Radiation Research

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Medical responders to radiological and nuclear disasters currently lack sufficient high-throughput and minimally invasive biodosimetry tools to assess exposure and injury in the affected populations. For this reason, we have focused on developing robust radiation exposure biomarkers in easily accessible biofluids such as urine, serum and feces. While we have previously reported on urine and serum biomarkers, here we assessed perturbations in the fecal metabolome resulting from exposure to external X radiation in vivo. The gastrointestinal (GI) system is of particular importance in radiation biodosimetry due to its constant cell renewal and sensitivity to radiation-induced injury. While the clinical GI symptoms such as pain, bloating, nausea, vomiting and diarrhea are manifested after radiation exposure, no reliable bioindicator has been identified for radiation-induced gastrointestinal injuries. To this end, we focused on determining a fecal metabolomic signature in X-ray irradiated mice. There is overwhelming evidence that the gut microbiota play an essential role in gut homeostasis and overall health. Because the fecal metabolome is tightly correlated with the composition and diversity of the microorganism in the gut, we also performed fecal 16S rRNA sequencing analysis to determine the changes in the microbial composition postir-radiation. We used in-house bioinformatics tools to integrate the 16S rRNA sequencing and metabolomic data, and to elucidate the gut integrated ecosystem and its deviations from a stable host-microbiome state that result from irradiation. The 16S rRNA sequencing results indicated that radiation caused remarkable alterations of the microbiome in feces at the family level. Increased abundance of common members of Lactobacillaceae and Staphylococcaceae families, and decreased abundances of Lachnospiraceae, Ruminococcaceae and Clostridiaceae families were found after 5 and 12 Gy irradiation. The metabolomic data revealed statistically significant changes in the microbial-derived products such as pipecolic acid, glutaconic acid, urobilinogen and homogentisic acid. In addition, significant changes were detected in bile acids such as taurocholic acid and 12-ketodeoxycholic acid. These changes may be associated with the observed shifts in the abundance of intestinal microbes, such as R. gnavus, which can transform bile acids.

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“…La régénération de l'intestin par les CSM peut-elle prévenir les effets néfastes, induits par l'irradiation, sur d'autres tissus du tube digestif tel que le foie ? Nous avons montré que l'irradiation induit une altération de l'intégrité hépatique, avec une élévation du taux des transaminases, associée à une augmentation du nombre de cellules lysées autour des vaisseaux et des canaux biliaires (Scanff et al 2004 ;Souidi et al 2007). L'injection de CSM permet le retour à la normale.…”

Section: Utilisation Des Csm De La Moelle Osseuse Dans Le Traitement unclassified

Cellules souches et médecine régénérative, application en radiobiologie

Chapel¹

2008

bavf

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La médecine régénérative a pour objectif de remplacer les tissus humains endommagés. Elle a pour principe de prélever et de purifier des cellules souches, de les multiplier in vitro, en maintenant leur multipotentialité pour les injecter ensuite dans l'organisme afin de leur faire fabriquer, directement, les tissus nécessaires à la réparation d'un organe, ou en orientant in vitro leur différenciation vers le tissu à traiter, avant de les injecter. Elle doit son essor aux récentes découvertes sur les cellules souches. Les perspectives sont le traitement de certains cancers, du diabète, des maladies dégénératives, des effets secondaires de la radiothérapie… Il existe des cellules souches à tous les stades du développement depuis l'oeuf fécondé jusqu'aux cellules souches adultes. Les cellules souches embryonnaires, parce qu'elles sont une source illimitée de cellules souches, semblent être l'avenir de la médecine régénérative. Cependant, parce qu'elles sont issues de l'embryon, elles sont au centre d'un débat éthique mondial. En revanche, les cellules souches adultes ne soulèvent pas de problèmes éthiques. Elles en sont déjà au stade de l'expérimentation clinique. Bien que présentes en nombres infimes, les cellules souches adultes sont facilement prélevées à partir de trois tissus : la moelle osseuse, le tissu adipeux et le muscle. Le nombre de leurs cellules souches peut être augmenté par des techniques simples. Le résultat le plus spectaculaire concerne la moelle osseuse, qui est utilisée depuis plus de quarante ans pour le traitement de la leucémie. L'Institut de Radioprotection et de Sûreté Nucléaire a participé à des études expérimentales contribuant à l'utilisation clinique des cellules souches mésenchymateuses dans le traitement des tissus sains irradiés. Deux éléments majeurs sont en train de révolutionner la médecine régénérative : les cellules souches mésenchymateuses sont utilisées comme moyen thérapeutique au même titre qu'un médicament et grâce à l'absence de leur rejet, un seul donneur permettrait de traiter de multiples receveurs dans de nombreuses pathologies ; la reprogrammation des cellules adultes différenciées permet d'obtenir des cellules souches aux propriétés analogues à celles des cellules souches embryonnaires (sources illimitées de cellules pluripotentes).

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Alteration of the enterohepatic recirculation of bile acids in rats after exposure to ionizing radiation

Cited by 6 publications

References 43 publications

The Metabolomic Approach Identifies a Biological Signature of Low-dose Chronic Exposure to Cesium 137

The Metabolomic Approach Identifies a Biological Signature of Low-dose Chronic Exposure to Cesium 137

An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host-Microbiome Axis

Cellules souches et médecine régénérative, application en radiobiologie

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