Analysis of Characteristic Indexes of Liver Injury Model Induced by Different Antituberculosis Drugs in Mice

Nihong LU; Honglu LIU; Yangjun CHEN; Meiyan LIU; Yongrui YANG; Yingrong DU

doi:10.12259/j.issn.2095-610X.S20230615

Volume 44 Issue 6

Jun. 2023

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Nihong LU, Honglu LIU, Yangjun CHEN, Meiyan LIU, Yongrui YANG, Yingrong DU. Analysis of Characteristic Indexes of Liver Injury Model Induced by Different Antituberculosis Drugs in Mice[J]. Journal of Kunming Medical University, 2023, 44(6): 6-13. doi: 10.12259/j.issn.2095-610X.S20230615

Citation:

Nihong LU, Honglu LIU, Yangjun CHEN, Meiyan LIU, Yongrui YANG, Yingrong DU. Analysis of Characteristic Indexes of Liver Injury Model Induced by Different Antituberculosis Drugs in Mice[J]. Journal of Kunming Medical University, 2023, 44(6): 6-13. doi: 10.12259/j.issn.2095-610X.S20230615

Citation:

Nihong LU, Honglu LIU, Yangjun CHEN, Meiyan LIU, Yongrui YANG, Yingrong DU. Analysis of Characteristic Indexes of Liver Injury Model Induced by Different Antituberculosis Drugs in Mice[J]. Journal of Kunming Medical University, 2023, 44(6): 6-13. doi: 10.12259/j.issn.2095-610X.S20230615

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Analysis of Characteristic Indexes of Liver Injury Model Induced by Different Antituberculosis Drugs in Mice

doi: 10.12259/j.issn.2095-610X.S20230615

The Third People’s Hospital of Kunming，Yunnan Provincial Clinical Medical Center for Infectious Diseases，Kunming Yunnan 650041，China

Received Date: 2023-03-23
Available Online: 2023-06-17
Publish Date: 2023-06-25

Abstract

Abstract

Objective To establish a mouse model of anti-tuberculous drug-induced liver injury, to explore the mechanism of anti-tuberculous drug induced liver injury, and to provide the basis of animal model. Methods Experimental mice were divided into 7 groups, including control group, group infected with Mycobacterium tuberculosis （MTB）, the other 5 groups were given different drugs after infection with MTB, namely isoniazid （INH） 45 mg/（kg·d）, rifampicin （RIF） 90 mg/（kg·d）, ethambutol （EB）135 mg/（kg·d）, pyrazinamide （PZA）180 mg/（kg·d）, tetrad antituberculosis drugs （INH+RIF+EB+PZA）, respectively. All doses were converted according to human dose and experimental animal dose. After 12 hours and 1-3 weeks of administration, the biochemical, liver index and pathological indexes were measured. Results After a single intragastric administration of INH, RIF, EB, PZA and tetrad anti-tuberculosis drugs for 12 hours, the levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in RIF group and tetrad group mice increased （P < 0.05）. After continuous intragastric administration of INH, RIF, EB, PZA and tetrad anti-tuberculosis drugs for 1 week, the serum indexes of ALT, AST and TBIL in the liver of INH, RIF and tetrad group mice were significantly increased （P < 0.05）, and the liver index and pathological range were gradually increased and enlarged （P < 0.05）. After continuous intragastric administration for 2-3 weeks, the serum indexes of liver ALT, AST, GGT and TBIL in INH, RIF and tetrad groups continued to increase （P < 0.05）, the liver index continued to increase （P < 0.05） and the range of lesions expanded （P < 0.05）. The correlation analysis showed that INH and RIF had a time cumulative effect, and the time of administration was significantly correlated with the serological index, liver index and lesion range of liver injury （P < 0.05）, while the time of administration in other groups was not significantly correlated with the liver injury index （P > 0.05）. Conclusion There is a trend of antagonistic liver toxicity among four combination anti-tuberculosis drugs, and INH and RIF are the main factors causing liver damage in mice. The pathological changes are mainly liver cell damage, and the abnormal degree of pathological indicators is earlier than serological indicators. The use of drugs to protect liver cell lesions in advance may have some clinical significance in preventing liver injury caused by anti-tuberculosis drugs.
- Anti-tuberculosis drugs,
- Liver injury,
- Mouse model,
- Indicators,
- Analysis

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