scholarly journals Differentiation of Necrotic Cell Death With or Without Lysosomal Activation: Application of Acute Liver Injury Models Induced by Carbon Tetrachloride (CCL4) and Dimethylnitrosamine (DMN)

2000 ◽  
Vol 48 (10) ◽  
pp. 1331-1339 ◽  
Author(s):  
Masanori Yasuda ◽  
Tsuyoshi Okabe ◽  
Johbu Itoh ◽  
Susumu Takekoshi ◽  
Hideaki Hasegawa ◽  
...  
2011 ◽  
Vol 31 (8) ◽  
pp. 1127-1136 ◽  
Author(s):  
Darren G. N. Craig ◽  
Patricia Lee ◽  
Elizabeth A. Pryde ◽  
Gail S. Masterton ◽  
Peter C. Hayes ◽  
...  

Cytokine ◽  
2016 ◽  
Vol 86 ◽  
pp. 21-28 ◽  
Author(s):  
Keisuke Kakisaka ◽  
Kojiro Kataoka ◽  
Yuji Suzuki ◽  
Yohei Okada ◽  
Yuichi Yoshida ◽  
...  

2019 ◽  
Vol 170 (2) ◽  
pp. 549-561 ◽  
Author(s):  
Matthew McMillin ◽  
Stephanie Grant ◽  
Gabriel Frampton ◽  
Anca D Petrescu ◽  
Elaina Williams ◽  
...  

Abstract Acute liver failure is a serious consequence of acetaminophen (APAP)-induced hepatotoxic liver injury with high rates of morbidity and mortality. Transforming growth factor beta 1 (TGFβ1) is elevated during liver injury and influences hepatocyte senescence during APAP-induced hepatotoxicity. This study investigated TGFβ1 signaling in the context of inflammation, necrotic cell death, and oxidative stress during APAP-induced liver injury. Male C57Bl/6 mice were injected with 600 mg/kg APAP to generate liver injury in the presence or absence of the TGFβ receptor 1 inhibitor, GW788388, 1 h prior to APAP administration. Acetaminophen-induced liver injury was characterized using histological and biochemical measures. Transforming growth factor beta 1 expression and signal transduction were assessed using immunohistochemistry, Western blotting and ELISA assays. Hepatic necrosis, liver injury, cell proliferation, hepatic inflammation, and oxidative stress were assessed in all mice. Acetaminophen administration significantly induced necrosis and elevated serum transaminases compared with control mice. Transforming growth factor beta 1 staining was observed in and around areas of necrosis with phosphorylation of SMAD3 observed in hepatocytes neighboring necrotic areas in APAP-treated mice. Pretreatment with GW788388 prior to APAP administration in mice reduced hepatocyte cell death and stimulated regeneration. Phosphorylation of SMAD3 was reduced in APAP mice pretreated with GW788388 and this correlated with reduced hepatic cytokine production and oxidative stress. These results support that TGFβ1 signaling plays a significant role in APAP-induced liver injury by influencing necrotic cell death, inflammation, oxidative stress, and hepatocyte regeneration. In conclusion, targeting TGFβ1 or downstream signaling may be a possible therapeutic target for the management of APAP-induced liver injury.


2000 ◽  
Vol 87 (5) ◽  
pp. 229-233 ◽  
Author(s):  
Beatrice Arosio ◽  
Nicoletta Gagliano ◽  
Lorena Maria Pia Fusaro ◽  
Luciano Parmeggiani ◽  
Jacopo Tagliabue ◽  
...  

Planta Medica ◽  
2009 ◽  
Vol 75 (09) ◽  
Author(s):  
CM Strüh ◽  
S Jäger ◽  
CM Schempp ◽  
T Jakob ◽  
A Scheffler ◽  
...  

Author(s):  
Haixia Yun ◽  
Xinyu Wu ◽  
Yiwei Ding ◽  
Wendou Xiong ◽  
Xianglan Duan ◽  
...  

Background and Objective : A Tibetan traditional herb named Swertia mussotii Franch., also called “Zangyinchen” by the local people of Qinghai-Tibet area, has been used to protect the liver from injury for many years. However, the curative effect and molecular mechanism of the herb have not been demonstrated clearly. Materials and Methods: In our study, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin levels were examined after S. mussotii Franch. treatment in the acute liver injury of the carbon tetrachloride-induced rat model. Then, Proteome Analysis was applied to explore the potential mechanism of SMT for hepatoprotective effects after iTRAQLC-MS/MS analysis (isobaric tag for relative and absolute quantification-liquid chromatograph-mass spectrometer with tandem mass spectrometry). Results: Serum results showed, alanine aminotransferase, aspartate aminotransferase, total bilirubin levels of rats with acute liver injury were all improved with SMT treatment. Moreover, Proteome Analysis suggested that, with S. Mussotii Franch. treatment, the levels of lipid catabolic process and lipid homeostasis were all enhanced. And the results of protein-protein interaction (PPI) analysis illustrated that these proteins assembled in PPI networks were found almost significantly enriched in response to lipid, negative regulation of lipase activity, response to lipopolysaccharide etc. Furthermore, the downregulated MRP14 and MRP8 proteins were found involved in the lipid metabolism, which may indicate the mechanism of SMT protection liver from ALI induced by carbon tetrachloride. Conclusion: SMT herb could play a role in hepatoprotection and alleviate the effect of acute liver injury by impacting the lipid metabolism associated biological process.


2021 ◽  
Vol 11 (1) ◽  
pp. 390
Author(s):  
Beom-Rak Choi ◽  
Il-Je Cho ◽  
Su-Jin Jung ◽  
Jae-Kwang Kim ◽  
Dae-Geon Lee ◽  
...  

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.


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