Carcinogenesis, Teratogenesis & Mutagenesis ›› 2022, Vol. 34 ›› Issue (1): 20-24.doi: 10.3969/j.issn.1004-616x.2022.01.004

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Injury effects of gatifloxacin in livers of mice based on transcriptome sequencing

GUO Ruixian1,3, XIE Guangyun2, HAN Ying3   

  1. 1. School of Pharmacy, Minzu University of China, Beijing 100081;
    2. Nationnal Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050;
    3. Division of Antibiotics, Institute for Chemical Drug Control, National Institutes for Food and Drug Control, Beijing 102629, China
  • Received:2021-08-24 Revised:2021-11-15 Online:2022-01-31 Published:2022-02-15

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Abstract: OBJECTIVE: To investigate the injury effects of gatifloxacin in livers of mice and its possible mechanisms of action. METHODS: Thirty-two SPF male Kunming mice were selected as the research objects and randomly divided into 4 groups:normal (saline),low-dose (25 mg/kg),medium-dose (50 mg/kg) and high-dose (100 mg/kg). The administration volume was 10 mL/kg,and the intragastric administration was continued for 7 days. The normal group was given the corresponding volume of normal saline. Through the detection of alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (AKP),creatinine (CRE) and triglyceride (TG) in the serum of each group of mice, the preliminary data indicated that gatifloxacin caused damage to liver tissues in mice. Therefore,the transcriptome sequencing technology was used to detect gene expression profiles in livers from each group,to screen differentially expressed genes,and to perform gene ontology (GO) functional classification of differential genes and Kyoto encyclopedia of genes and genomes (KEGG) signal pathway enrichment analysis. RESULTS: Compared with the normal group,the qualities of the livers from the high-dose group were significantly reduced (P<0.01),and the liver coefficients for the low- and medium-dose groups were significantly reduced (P<0.01). The serum ALT levels from the high-dose group were significantly reduced (P<0.01);the serum AST levels from the middle and high-dose groups were significantly reduced (P<0.01). Compared with the normal group,a total of 27 differentially expressed genes (including 20 up-regulated genes and 7 down-regulated genes) were screened out in the medium-dose group. GO functional classifications suggest that these genes were mainly enriched in 17 biological processes including the immune system,multicellular organisms,and multibiological processes. KEGG pathway analyses indicate that the differential genes were mainly enriched in 22 pathways including lipid metabolism,terpenoids and polyketide metabolism. CONCLUSION: Gatifloxacin caused alterations in liver functions of mice by affecting the balance of endocrine system such as bile acid and cholesterol and lipid metabolism in the liver of mice.

Key words: gatifloxacin, hepatotoxicity, transcriptomics, differentially expressed genes, mice

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