Loperamide Induces Excessive Accumulation of Bile Acids in the Liver of Mice with Different Diets

Toxicology. 2022 Aug 1:153278. doi: 10.1016/j.tox.2022.153278. Online ahead of print.ABSTRACTLoperamide is a non-prescription medicine normally used for the treatment of diarrhea. The abuse and misuse of loperamide have been demonstrated to have toxic effects on heart. It is still unclear whether the abuse of loperamide can cause hepatic toxicity. The C57BL/6 mice fed with high fat diet (HFD) or normal food diet (NFD) were administrated with loperamide (5mg/kg/day) intragastrically once a day for two weeks, after that, the feces, blood, hepatic tissues and intestines were harvested for biochemical and histological detection, and the expression of genes related with lipid metabolism was further checked by qRT-PCR (quantitative real-time polymerase chain reaction) and Western blot. The administration of loperamide caused the constipation in mice fed with NFD or HFD. The content of bile acids was significantly reduced in the feces of mice treated with loperamide, but the content of bile acids was significantly increased in the liver of these mice. The results of H&E staining showed that loperamide administration caused the damage of hepatic tissues, especially for mice fed with HFD. The expression of genes related with the biosynthesis of cholesterol and bile acids, including Hmgcr, Lss, Sqle, Fdps, Idi1, Mvk, Cyp7a1 and Ch25h, was all upregulated in the liver of mice treated with loperamide. Conversely, the expression of Abcg5, Abcb11 and Abcc2, which encode genes for trans...

Source: Toxicology - August 4, 2022 Category: Toxicology Authors: Zili Lei Hedong Rong Yanhong Yang Siping Yu Tianle Zhang Lei Chen Ya Nie Qi Song Qing Hu Jiao Guo Source Type: research