Arsenic (As) is known to induce toxic responses in many organs of human beings and animals. However, research concerning toxicity in the stomach is limited. In this study,
arsenic-induced gastric toxicity was investigated in a mouse model, and grape skin extract (GSE) was confirmed to have protective effects against
arsenic toxicity. Our experimental results showed that exposure to 10 mg/l
arsenic via
drinking water for 56 days caused oxidative damage and inflammatory responses. The H2O2 and
malondialdehyde (MDA) contents were significantly increased, accompanied by significant decreases in total
superoxide dismutase (T-SOD) activity and
glutathione (GSH) content in the gastric tissue of
arsenic-treated mice. Two inflammatory signalling pathways, i.e., TLR2/MyD88/NF-κB and IL-6/STAT-3, were activated, along with inflammatory cell infiltration and the elevated
mRNA expression of pro-inflammatory
cytokines (TNF-α, IL-1β and IFN-γ) and
myeloperoxidase (MPO) in the gastric tissue of mice exposed to
arsenic. Meanwhile, the
mRNA levels of the ZO-1, ZO-2 and
occludin genes, which encode the key components of tight junction (TJ) complexes, were downregulated. However, the application of GSE (300 mg/kg bw) significantly inhibited the
arsenic-induced increases in H2O2 and MDA contents and the decreases in T-SOD activity and GSH content. The
arsenic-mediated gene expression of pro-inflammatory
cytokines (TNF-α, IL-1β and IFN-γ), MPO and IL-6/STAT3 and TLR2/MyD88/NF-κB pathways was found down-regulated. Moreover, the
arsenic-induced inflammatory cell infiltration and inhibition of TJ genes transcription were markedly attenuated in the As+GSE (300 mg/kg bw) group. Based on the present findings,
arsenic intake appears to cause gastric toxicity via oxidative stress and
inflammation, and the application of GSE offers significant protection against
arsenic toxicity in a mouse model by attenuating the oxidative stress and inflammatory response. Our results suggest that GSE by
oral administration might function as a candidate therapeutic supplement to antagonize
arsenic toxicity.