RESUMEN
Alternariol monomethyl-ether (AME), together with altenuene and alternariol, belongs to the Alternaria mycotoxins group, which can contaminate different substrates, including cereals. The aim of the present study was to obtain a deeper understanding concerning the effects of AME on pig intestinal health using epithelial intestinal cell lines as the data concerning the possible effects of Alternaria toxins on swine are scarce and insufficient for assessing the risk represented by Alternaria toxins for animal health. Our results have shown a dose-related effect on IPEC-1 cell viability, with an IC50 value of 10.5 µM. Exposure to the toxin induced an increase in total apoptotic cells, suggesting that AME induces programmed cell death through apoptosis based on caspase-3/7 activation in IPEC-1 cells. DNA and protein oxidative damage triggered by AME were associated with an alteration of the antioxidant response, as shown by a decrease in the enzymatic activity of catalase and superoxide dismutase. These effects on the oxidative response can be related to an inhibition of the Akt/Nrf2/HO-1 signaling pathway; however, further studies are needed in order to validate these in vitro data using in vivo trials in swine.
Asunto(s)
Apoptosis , Supervivencia Celular , Células Epiteliales , Lactonas , Estrés Oxidativo , Animales , Estrés Oxidativo/efectos de los fármacos , Porcinos , Línea Celular , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Supervivencia Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Lactonas/toxicidad , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismoRESUMEN
Oxidative stress is a pivotal factor in the pathogenesis of intestinal inflammation, leading to cellular damage and tissue injury. Natural antioxidants compounds found in agro-industrial by-products have proven their effectiveness in treatment of intestinal inflammation and oxidative stress, exhibiting many favourable effects. The aim of this study was to evaluate the capacity of a grape seed meal byproduct (GSM) to counteract the effects induced by E. coli lipopolysaccharide (LPS, 5µg/ml) in vitro on IPEC-1 cells and by dextran sulphate sodium (DSS, 1g/b.w./day) in vivo on piglets after weaning. Reactive oxygen species (ROS), pro-oxidant markers (malondialdehyde MDA, thiobarbituric acid reactive substances TBARS, protein carbonyl, DNA oxidative damage) antioxidant enzymes (catalase -CAT, superoxide dismutase -SOD, glutathione peroxidase -GPx, endothelial and inducible nitric oxide synthases -eNOS and iNOS) and several important components of Keap1/Nrf2 signalling pathway were analysed in IPEC-1 cells as well as in piglet's colon and lymph nodes. Our results demonstrated that GSM extract or 8% dietary GSM showed anti-oxidant properties counteracting the pro-oxidant response (ROS, MDA-TBARS, protein carbonyl, DNA/RNA damage) induced by LPS or DSS and restoring the levels of endogenous antioxidant enzymes, including CAT, SOD, GPx, eNOS and iNOS in colon and mesenteric lymph nodes. These beneficial effects were modulated via Nrf2 signalling pathway in both in vitro and in vivo studies.