Ecotoxicology and Environmental Safety (Mar 2022)
Arsenic intake-induced gastric toxicity is blocked by grape skin extract by modulating inflammation and oxidative stress in a mouse model
Abstract
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.
