Liver and Kidney Toxicity of Celastrol and Its Regulating Action of Gut Microbiota on a High-fat Diet Mice
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Abstract:
The effects of a high-fat diet and celastrol treatment on gut microbiota and liver and kidney toxicity in mice were examined. Mice were fed a normal or high-fat rat diet, with a celastrol treatment at high, medium and low doses. High-throughput sequencing was used to analyze the intestinal flora of mice, and the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the contents of creatinine (Cr) and blood urea nitrogen (Bun) were measured. Studies have shown that a high-fat diet and celastrol treatment significantly affect the composition of gut microbiota in mice. The high-fat diet reduced significantly the abundance and diversity of gut microbiota in mice. The celastrol treatment increased the abundance and diversity of gut microbiota in the mice fed the high-fat diet, while enriching the bacteria of the genus Ruminiclostridium and Anaerotruncus. Compared to the control group, the contents of Ruminiclostridium and Anaerotruncus in the low-, medium- and high-dose groups increased by 51.26%, -44.62% and 129.98%, and 62.45%, 28.73% and 17.86%, respectively. The treatment with celastrol at 100~400 μg/kg led to insignificant changes in the AST and ALT activities, and Cr and Bun contents. These results showed that the high-fat diet and celastrol treatment affected significantly the gut microbial structure of mice, and celastrol exhibited imsignificant toxicity at the treatment dose of 100~400 μg/kg.