Validation of a surgical technique for rat intestinal irradiation: potential side effects prevention by dietary grape phenolics.

AIMS: This study evaluates and defines the histological and biochemical consequences of irradiation on the Hauer-Jensen intestinal model and investigates the potential effects of dietary polyphenols. MAIN METHODS: Sprague-Dawley rats were orchiectomized, and an ileal loop was transposed to the left part of the scrotum, then irradiated 2 weeks after surgery with a single dose of 21 Gy (4.49 Gy/min). Four groups of rats received either phenolic extracts from grape seeds (EGS) and from red wine (ACYS, EGT), or pure quercetin 3-O-ß-glucoside (Q3G), for 5 days before the irradiation and were sacrificed 2 weeks after. Antioxidant enzyme activities, i.e. superoxide dismutase (SOD) and glutathione peroxidase activity (GSHPx), and oxidative markers such as myeloperoxidase activity (MPO) and thiobarbituric acid reactive substances (MDA) were measured as well as cytokine-induced neutrophil chemoattractant level (CINC-1), a chemokine involved in inflammation. KEY FINDINGS: Irradiated rats exhibited a high radiation injury score (RIS) with a thickened serosa, mucosal loss and ulceration, and epithelial atypicality. Intestinal MPO activity and CINC-1 concentration were significantly increased in irradiated animals (60 and 66 %, respectively). Higher plasma MDA levels (58 %) and SOD activity (32 %) were accompanied by a reduced GSHPx activity (79 %). However, feeding phenolic extracts remarkably reduced levels of blood SOD activity (34 % on average), intestinal CINC-1 (25-75 % range) and MPO activity (36-84 %). Except for Q3G, phenolics preserved the intestinal structure. SIGNIFICANCE: These findings show that irradiation triggers an inflammation, and an oxidative stress by disturbing the pro-oxidant/antioxidant balance and indicate that phenolics supply exerts preventive effects against radio-induced intestinal impairment.

Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: stimulation of interleukin-8 secretion, potentiation of interleukin-1beta effect and increase in the transepithelial passage of commensal bacteria.

Mycotoxins are fungal secondary metabolites responsible of food-mediated intoxication in animals and humans. Deoxynivalenol, ochratoxin A and patulin are the best known enteropathogenic mycotoxins able to alter intestinal functions resulting in malnutrition, diarrhea, vomiting and intestinal inflammation in vivo. Although their effects on intestinal barrier and transport activities have been extensively characterized, the mechanisms responsible for their pro-inflammatory effect are still poorly understood. Here we investigated if mycotoxin-induced intestinal inflammation results from a direct and/or indirect pro-inflammatory activity of these mycotoxins on human intestinal epithelial cells, using differentiated Caco-2 cells as model and interleukin 8 (IL-8) as an indicator of intestinal inflammation. Deoxynivalenol was the only mycotoxin able to directly increase IL-8 secretion (10- to 15-fold increase). We also investigated if these mycotoxins could indirectly stimulate IL-8 secretion through: (i) a modulation of the action of pro-inflammatory molecules such as the interleukin-1beta (IL-1beta), and/or (ii) an increase in the transepithelial passage of non-invasive commensal Escherichia coli. We found that deoxynivalenol, ochratoxin A and patulin all potentiated the effect of IL-1beta on IL-8 secretion (ranging from 35% to 138% increase) and increased the transepithelial passage of commensal bacteria (ranging from 12- to 1544-fold increase). In addition to potentially exacerbate established intestinal inflammation, these mycotoxins may thus participate in the induction of sepsis and intestinal inflammation in vivo. Taken together, our results suggest that the pro-inflammatory activity of enteropathogenic mycotoxins is mediated by both direct and indirect effects.