Objective:To investigate the arsenic-induced small intestinal toxicity and the protective effect of grape skin extract(GSE)against arsenic toxicity.Methods:The small intestinal toxicity was induced by 10 mg/L arsenic via drinking water for 56 days,and was intervened with GSE(150 mg/kg bw and 300 mg/kg bw)by gavage every other day in mice.Small intestine tissue samples of mice were collected and observed by microscope.Glutathione(GSH),malondialdehyde(MDA)and H2O2 contents,as well as total superoxide dismutase(T-SOD)were determined by using commercial kits.qRT-PCR was used to detect expression levels of the tight junction genes and the inflammatory pathway IL-6/JAK2/STAT-3 genes.Results:The results showed that 56 days exposure to 10 mg/L arsenic via drinking water resulted in shortened and disordered intestinal villi,with large numbers of inflammatory cells infiltrating the mucosa propria and submucosa.GSH content and T-SOD activity decreased by 17.1%and 25.2%,while MDA and H2O2 contents increased by 68.8%and 54.3%,respectively(P<0.05)in the small intestinal tissue of arsenic-treated mice.The mRNA levels of IL-6,JAK2 and STAT-3 were upregulated in the small intestinal tissue of mice exposed to arsenic(P<0.05).Meanwhilethe mRNA levels of the ZO-1,ZO-2,occludin,claudin1 and claudin7 genes,which encode the key components of tight junction(TJ)complexes,were downregulated(P<0.05).However,the application of GSE(300 mg/kg bw)significantly alleviated the damage and inflammatory infiltration in small intestine.Compare to the As group,GSH content and T-SOD activity increased by 17.9%and 14.3%.MDA and H2O2 contents decreased by 33.8%and 25.4%(P<0.05).Arsenic-mediated gene expression in the IL-6/JAK2/STAT3 pathway was down-regulated(P<0.05).Moreover,the arsenic-induced down-regulation of TJ genes were markedly relieved in the As+GSE(300 mg/kg bw)group(P<0.05).The As+GSE(150 mg/kg bw)group had a certain alleviating effect on arsenic toxicity,but the difference had no statistical significance(P>0.05).Conclusion:The application of GSE provides significant protection against arsenic-induced small intestinal toxicity by attenuating the oxidative stress and inflammatory responses,and inhibiting the down-regulation of some functional genes.
维普
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