Induction of Nuclear Factor κB in Different First-Line Anti-tubercular Drug-induced Liver Injuries in Mice
Induction of Nuclear Factor κB in Different First-Line Anti-tubercular Drug-induced Liver Injuries in Mice
Yuhong Li1, Dongxue Wu1, Xue Wang1, Mi Zhang1, Hanyu Zhu1, Zhe Shi1 and Fumin Feng1,2*
ABSTRACT
Nuclear factor κB (NF-κB) regulates the gene expression of eukaryotic cells. This study aims to reveal the changes in NF-κB during the development and progression of liver injury induced by anti-tuberculosis drugs in mice. A total of 168 Kunming mice were randomly divided into four experimental groups and one baseline group. The drug groups were orally administered with isoniazid (H), rifampicin (R), pyrazinamide (Z), and combination of these three drugs (HRZ) at 3, 5, 7, 10, and 15 days, respectively. Liver tissue pathologies and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities changed, indicating the occurrence of liver injury. Compared with the baseline group, the content of malondialdehyde (MDA) in each drug group gradually increased, and the activity of superoxide dismutase (SOD) gradually decreased, suggesting that oxidative stress reaction occurred in all drug groups. Compared with the baseline group, the mRNA and protein levels of NF-κB and TNF-α in the H group showed an increasing trend, and p-NF-κB and p-IκB also showed an increasing trend. However, these indicators increased first and then slightly decreased in the R, Z and HRZ groups. Among them, the significant changes in the indicators of the HRZ group were earlier than those of other drug groups and the changes were most obvious. The mRNA and protein of IκB in each drug group showed a gradual decline. The NF-κB pathway is activated in different mouse models of first-line anti-tuberculosis drug-induced liver injury and the activation level is different in each drug group. Among them, the NF-κB activation level of the combination therapy group is the highest, and the damage to hepatocyte is more serious than the single drug.
To share on other social networks, click on any share button. What are these?
October 2020
Vol. 52, Iss. 5, Pages 1631-2026
