Pre-Exposure to TiO2-NPs Aggravates Alcohol-Related Liver Injury by Inducing Intestinal Barrier Damage in Mice

The wide application of titanium dioxide nanoparticles (TiO2-NPs) and the increase in opportunities for its release into the environment undoubtedly compound the potential of these materials to harm people. Research on the effects of pre-exposure to TiO2-NPs on disease development is scarce. The purpose of this work was to assess whether pre-exposure to TiO2-NPs (20 and 200 mg/kg) for 28 days aggravates the development of alcohol-related liver injury in mice. Results showed that oral administration of 200 mg/kg TiO2-NPs induced only modest changes in liver function parameters, but could induce intestinal inflammation and destroy the integrity of intestinal barrier. After the subsequent alcohol intervention, pre-exposure to TiO2-NPs (200 mg/kg) was found to aggravate alcohol-related liver injury, including significantly increases in serum aspartate aminotransferase, alanine aminotransferase, total glycerol, and total cholesterol, as well as steatosis and inflammation in the liver. Further investigation revealed that alcohol could increase intestinal permeability and reduce the expression of tight junction proteins in mice pre-exposed high dosage of TiO2-NPs, thereby inducing the transfer of more lipopolysaccharides into the liver, ultimately triggering more severe liver inflammation. This study emphasizes that pre-exposed of TiO2-NPs (high doses of up to 200 mg/kg) can potentially promote the development of alcoholic liver diseases. Furthermore, this study provides new insights into evaluating the safety of NPs.