Propylthiouracil-Induced Liver Injury in Mice and the Protective Role of Taurine

Nitric oxide (NO) is suggested to play a role in liver injury elicited by acetaminophen (APAP). Hepatic microcirculatory dysfunction also is reported to contribute to the development of the injury. As a result, the role of NO in hepatic microcirculatory alterations in response to APAP was examined in mice by in vivo microscopy. A selective inducible NO synthase (iNOS) inhibitor,l- N6-(1-iminoethyl)-lysine (l-NIL), or a nonselective NOS inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), was intraperitoneally administered to animals 10 min before APAP gavage. l-NIL suppressed raised alanine aminotransferase (ALT) values 6 h after APAP, whereas l-NAME increased those 1.7-fold. Increased ALT levels were associated with hepatic expression of iNOS. l-NIL, but not l-NAME, reduced the expression. APAP caused a reduction (20%) in the numbers of perfused sinusoids. l-NIL restored the sinusoidal perfusion, but l-NAME was ineffective. APAP increased the area occupied by infiltrated erythrocytes into the extrasinusoidal space. l-NIL tended to minimize this infiltration, whereas l-NAME further enhanced it. APAP caused an increase (1.5-fold) in Kupffer cell phagocytic activity. This activity in response to APAP was blunted by l-NIL, whereas l-NAME further elevated it. l-NIL suppressed APAP-induced decreases in hepatic glutathione levels. These results suggest that NO derived from iNOS contributes to APAP-induced parenchymal cell injury and hepatic microcirculatory disturbances. l-NIL exerts preventive effects on the liver injury partly by inhibiting APAP bioactivation. In contrast, NO derived from constitutive isoforms of NOS exerts a protective role in liver microcirculation against APAP intoxication and thereby minimizes liver injury.

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Sophocarpine Attenuates LPS-Induced Liver Injury and Improves Survival of Mice through Suppressing Oxidative Stress, Inflammation, and Apoptosis

Mediators of Inflammation ◽

10.1155/2018/5871431 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 11

Author(s):

Zhengyu Jiang ◽

Yan Meng ◽

Lulong Bo ◽

Changli Wang ◽

Jinjun Bian ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Great Part ◽

Protective Role ◽

Stress Indicators ◽

Oxidative Reaction ◽

Hepatic Expression ◽

Jnk Cascade ◽

Oxidative Stress Indicators

Septic liver injury/failure that is mainly characterized by oxidative stress, inflammation, and apoptosis led to a great part of terminal liver pathology with limited effective intervention. Here, we used a lipopolysaccharide (LPS) stimulation model to simulate the septic liver injury and investigated the effect of sophocarpine on LPS-stimulated mice with endotoxemia. We found that sophocarpine increases the survival rate of mice and attenuates the LPS-induced liver injury, which is indicated by pathology and serum liver enzymes. Further research found that sophocarpine ameliorated hepatic oxidative stress indicators (H2O2, O2∙−, and NO) and enhanced the expression of antioxidant molecules such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). In addition, sophocarpine also attenuated regional and systematic inflammation and further reduced apoptosis of hepatocytes. Mechanistic evidence was also investigated in the present study as sophocarpine inhibited hepatic expression of the CYP2E/Nrf2 pathway during oxidative stress, inactivated p38/JNK cascade and NF-κB pathway, and, meanwhile, suppressed PI3K/AKT signaling that reduced apoptosis. Conclusively, the present study unveiled the protective role of sophocarpine in LPS-stimulated oxidative reaction, inflammation, and apoptosis by suppressing the CYP2E/Nrf2/ROS as well as PI3K/AKT pathways, suggesting its promising role in attenuating inflammation and liver injury of septic endotoxemia.

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The protective role of Hepatopoietin Cn on liver injury induced by carbon tetrachloride in rats

Hepatology Research ◽

10.1111/j.1872-034x.2008.00447.x ◽

2009 ◽

Vol 39 (2) ◽

pp. 200-206 ◽

Cited By ~ 11

Author(s):

Chun-Ping Cui ◽

Ping Wei ◽

Yang Liu ◽

Da-Jin Zhang ◽

Li-Sheng Wang ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Protective Role

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The protective role of pregnane X receptor in lipopolysaccharide/D-galactosamine-induced acute liver injury

Laboratory Investigation ◽

10.1038/labinvest.2009.129 ◽

2009 ◽

Vol 90 (2) ◽

pp. 257-265 ◽

Cited By ~ 41

Author(s):

Kun Wang ◽

Ivan Damjanov ◽

Yu-Jui Yvonne Wan

Keyword(s):

Liver Injury ◽

Acute Liver Injury ◽

Pregnane X Receptor ◽

Protective Role

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Hepatic progenitor cells promote the repair of schistosomiasis liver injury by inhibiting IL-33 secretion in mice

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02589-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Beibei Zhang ◽

Xiaoying Wu ◽

Jing Li ◽

An Ning ◽

Bo Zhang ◽

...

Keyword(s):

Liver Injury ◽

Progenitor Cells ◽

Normal Liver ◽

Protective Role ◽

Dependent Manner ◽

Hepatic Progenitor Cells ◽

Wild Type ◽

Mice Model

Abstract Background Hepatic schistosomiasis, a chronic liver injury induced by long-term Schistosoma japonicum (S. japonicum) infection, is characterized by egg granulomas and fibrotic pathology. Hepatic progenitor cells (HPCs), which are nearly absent or quiescent in normal liver, play vital roles in chronic and severe liver injury. But their role in the progression of liver injury during infection remains unknown. Methods In this study, the hepatic egg granulomas, fibrosis and proliferation of HPCs were analyzed in the mice model of S. japonicum infection at different infectious stages. For validating the role of HPCs in hepatic injury, tumor necrosis factor-like-weak inducer of apoptosis (TWEAK) and TWEAK blocking antibody were used to manipulate the proliferation of HPCs in wild-type and IL-33−/− mice infected with S. japonicum. Results We found that the proliferation of HPCs was accompanied by inflammatory granulomas and fibrosis formation. HPCs expansion promoted liver regeneration and inhibited inflammatory egg granulomas, as well as the deposition of fibrotic collagen. Interestingly, the expression of IL-33 was negatively associated with HPCs’ expansion. There were no obvious differences of liver injury caused by infection between wild-type and IL-33−/− mice with HPCs’ expansion. However, liver injury was more attenuated in IL-33−/− mice than wild-type mice when the proliferation of HPCs was inhibited by anti-TWEAK. Conclusions Our data uncovered a protective role of HPCs in hepatic schistosomiasis in an IL-33-dependent manner, which might provide a promising progenitor cell therapy for hepatic schistosomiasis.

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