‘In‐field’ and ‘out‐of‐field’ functional impairment during subacute and chronic phases of experimental radiation enteropathy in the rat

François, Agnès; Milliat, Fabien; Vozenin, Marie-Catherine; Mathé, Denis; Griffiths, N. M.

doi:10.1080/0955300031000150594

Cited by 13 publications

(6 citation statements)

References 52 publications

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“…To avoid these complications, we used lower doses in our preliminary (1 and 5 Gy; V. Douard, A. Muduli, R. W. Howell, R. P. Ferraris, unpublished data) and present studies (7, 8.5, and 10 Gy), and we measured uptake on postirradiation days when the mucosa was still intact, even at doses (e.g., 10 Gy) that may eventually lead to mucosal alterations at a later date. In fact, by 14 days postirradiation, weight per centimeter intestine of some mice exposed to 8.5 Gy has already decreased by ϳ25% (data not shown), suggesting loss of mucosa so often observed in radiation poisoning (21,33).…”

Section: Radiation-induced Reductions In Sugar Transportmentioning

confidence: 91%

“…However, it is only at highradiation doses that the number of cells entering the villus from the crypt becomes insufficient to maintain the enterocyte population and consequently leads to decrease in villus heights. For example, localized irradiation of rat intestinal segments with 18, 21, or 29.6 Gy resulted in epithelial denudation followed by mucosal ulceration and by intestinal fibrosis (21). At these doses, all types of nutrient transport would decrease.…”

Section: Radiation-induced Reductions In Sugar Transportmentioning

confidence: 99%

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Radiation-induced reductions in transporter mRNA levels parallel reductions in intestinal sugar transport

Roche

Neti

Kemp

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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More than a century ago, ionizing radiation was observed to damage the radiosensitive small intestine. Although a large number of studies has since shown that radiation reduces rates of intestinal digestion and absorption of nutrients, no study has determined whether radiation affects mRNA expression and dietary regulation of nutrient transporters. Since radiation generates free radicals and disrupts DNA replication, we tested the hypotheses that at doses known to reduce sugar absorption, radiation decreases the mRNA abundance of sugar transporters SGLT1 and GLUT5, prevents substrate regulation of sugar transporter expression, and causes reductions in sugar absorption that can be prevented by consumption of the antioxidant vitamin A, previously shown by us to radioprotect the testes. Mice were acutely irradiated with (137)Cs gamma rays at doses of 0, 7, 8.5, or 10 Gy over the whole body. Mice were fed with vitamin A-supplemented diet (100x the control diet) for 5 days prior to irradiation after which the diet was continued until death. Intestinal sugar transport was studied at days 2, 5, 8, and 14 postirradiation. By day 8, d-glucose uptake decreased by approximately 10-20% and d-fructose uptake by 25-85%. With increasing radiation dose, the quantity of heterogeneous nuclear RNA increased for both transporters, whereas mRNA levels decreased, paralleling reductions in transport. Enterocytes of mice fed the vitamin A supplement had > or = 6-fold retinol concentrations than those of mice fed control diets, confirming considerable intestinal vitamin A uptake. However, vitamin A supplementation had no effect on clinical or transport parameters and afforded no protection against radiation-induced changes in intestinal sugar transport. Radiation markedly reduced GLUT5 activity and mRNA abundance, but high-d-fructose diets enhanced GLUT5 activity and mRNA expression in both unirradiated and irradiated mice. In conclusion, the effect of radiation may be posttranscriptional, and radiation-damaged intestines can still respond to dietary stimuli.

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Section: Radiation-induced Reductions In Sugar Transportmentioning

confidence: 91%

Section: Radiation-induced Reductions In Sugar Transportmentioning

confidence: 99%

Radiation-induced reductions in transporter mRNA levels parallel reductions in intestinal sugar transport

Roche

Neti

Kemp

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Radiation-damaged tissues, included during the late fibroatrophic phase, often present sustained oxidative stress [28], and the protective effects of probiotics in the pathogenesis of radiation injury to the digestive tract may in part rely on their antioxidant properties [29]. Neutrophil influx is observed in the rat small intestine until 26 weeks after exposure to localized single (18, 21, 29.6 Gy) or fractionated (16 × 4.2 Gy) X-radiation [30, 31]. In mice, radiation proctitis following 27 Gy single-dose exposure shows increased neutrophil numbers in the inflamed and fibrosed areas 2 and 14 weeks postirradiation.…”

Section: Radiation-induced Inflammationmentioning

confidence: 99%

Inflammation and Immunity in Radiation Damage to the Gut Mucosa

François

Milliat

Guipaud

et al. 2013

BioMed Research International

107

103

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Erythema was observed on the skin of the first patients treated with radiation therapy. It is in particular to reduce this erythema, one feature of tissue inflammation, that prescribed dose to the tumor site started to be fractionated. It is now well known that radiation exposure of normal tissues generates a sustained and apparently uncontrolled inflammatory process. Radiation-induced inflammation is always observed, often described, sometimes partly explained, but still today far from being completely understood. The thing with the gut and especially the gut mucosa is that it is at the frontier between the external milieu and the organism, is in contact with a plethora of commensal and foreign antigens, possesses a dense-associated lymphoid tissue, and is particularly radiation sensitive because of a high mucosal turnover rate. All these characteristics make the gut mucosa a strong responsive organ in terms of radiation-induced immunoinflammation. This paper will focus on what has been observed in the normal gut and what remains to be done concerning the immunoinflammatory response following localized radiation exposure.

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“…This process adds to the oxidative stress induced by the radiolysis of water and reduces the regenerative capacities of the tissue. In rodent models, localized single-dose or fractionated radiation leads to an influx of neutrophils 1 week after irradiation and lasts up to 26 weeks (54,66). This influx is associated with increased expression of molecules having strong neutrophil chemoattractant activity after colorectal irradiation (14,20).…”

Section: Pathophysiology Of Intestinal Radiation Damagementioning

confidence: 99%

Bowel Radiation Injury: Complexity of the Pathophysiology and Promises of Cell and Tissue Engineering

et al. 2016

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Ionizing radiation is effective to treat malignant pelvic cancers, but the toxicity to surrounding healthy tissue remains a substantial limitation. Early and late side effects not only limit the escalation of the radiation dose to the tumor but may also be life-threatening in some patients. Numerous preclinical studies determined specific mechanisms induced after irradiation in different compartments of the intestine. This review outlines the complexity of the pathogenesis, highlighting the roles of the epithelial barrier in the vascular network, and the inflammatory microenvironment, which together lead to chronic fibrosis. Despite the large number of pharmacological molecules available, the studies presented in this review provide encouraging proof of concept regarding the use of mesenchymal stromal cell (MSC) therapy to treat radiation-induced intestinal damage. The therapeutic efficacy of MSCs has been demonstrated in animal models and in patients, but an enormous number of cells and multiple injections are needed due to their poor engraftment capacity. Moreover, it has been observed that although MSCs have pleiotropic effects, some intestinal compartments are less restored after a high dose of irradiation. Future research should seek to optimize the efficacy of the injected cells, particularly with regard to extending their life span in the irradiated tissue. Moreover, improving the host microenvironment, combining MSCs with other specific regenerative cells, or introducing new tissue engineering strategies could be tested as methods to treat the severe side effects of pelvic radiotherapy.

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‘In‐field’ and ‘out‐of‐field’ functional impairment during subacute and chronic phases of experimental radiation enteropathy in the rat

Cited by 13 publications

References 52 publications

Radiation-induced reductions in transporter mRNA levels parallel reductions in intestinal sugar transport

Radiation-induced reductions in transporter mRNA levels parallel reductions in intestinal sugar transport

Inflammation and Immunity in Radiation Damage to the Gut Mucosa

Bowel Radiation Injury: Complexity of the Pathophysiology and Promises of Cell and Tissue Engineering

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