Application of the PKCYP Test to Predict Caffeine Clearance Mediated by CYP1A2 in a Rat Acute Liver Injury Model

2003 ◽  
Vol 18 (5) ◽  
pp. 296-302 ◽  
Author(s):  
Noriko Kose ◽  
Minae Isawa ◽  
Junko Kizu ◽  
Norio Miyazaki ◽  
Akira Takanaka ◽  
...  
2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Chunguang Wang ◽  
Tie Zhang ◽  
Xuemei Cui ◽  
Shuang Li ◽  
Xinghua Zhao ◽  
...  

The objective of this study is to establish poultry liver injury model induced by (CCl4) and seek effective hepatoprotective herbals for clinical application. Different doses of CCl4dissolved in vegetable oil (1 : 1,V/V) were injected via pectoral muscle to induce acute liver injury model in chickens. An herbal formula, Longyin decoction, was prepared for hepatoprotection test on chicken acute liver injury models. The pathologic changes of the liver were observed, and the activities of ALT and AST were, respectively, detected to evaluate the hepatoprotective effects of Longyin decoction on chickens. The chicken acute liver injury model was successfully established by injecting CCl4via pectoral muscle. The best dose of CCl4inducing chicken liver injury was 4.0 mL/kg·BW (body weight). The results of qualitative determination by HPTLC showed that the components of Longyin decoction containedGentian, Capillaries, Gardenia,andBupleurum root. In the high-dose Longyin group and the middle-dose Longyin group, the pathological changes of the damaged liver were mitigated and the activities of ALT and AST in serum were reduced significantly. Longyin decoction has obvious hepatoprotective effect on acute liver injury induced by CCl4.


2020 ◽  
Vol 98 (3) ◽  
pp. 162-168 ◽  
Author(s):  
Yong-mei Jin ◽  
Xiang-ming Tao ◽  
Yi-ning Shi ◽  
Youjin Lu ◽  
Jin-yu Mei

Salvianolic acid B (Sal B) exerts strong antioxidant activity and eliminates the free radical effect. However, how it affects the antioxidant pathway is not very clear. The objective of this study was to investigate the underlying mechanism of Sal B in CCl4-induced acute liver injury, especially its effect on the Nrf2/HO-1 signaling pathway. For the in vivo experiment, an acute liver injury model was induced using CCl4 and treated with Sal B. For the in vitro experiment, an oxidative damage model was established followed by Sal B treatment. Serum biochemical indicators and reactive oxygen species activity were detected using corresponding kits. Oxidant/antioxidant status was determined based on the levels of malondialdehyde, glutathione, and superoxide dismutase. Nrf2 and HO-1 levels were analyzed by Western blotting and immunohistochemical staining. Sal B treatment improved liver histology, decreased the aminotransferase levels, and attenuated oxidative stress in the acute liver injury model. Nrf2 and HO-1 levels were increased both in vivo and in vitro. Sal B suppresses acute liver injury and Nrf2/HO-1 signaling plays a key role in this process.


2017 ◽  
Vol 66 (1) ◽  
pp. S656-S657
Author(s):  
Y.J. Chae ◽  
D.W. Jun ◽  
S.B. Ahn ◽  
W.K. Saeed ◽  
J.S. Lee ◽  
...  

Redox Biology ◽  
2021 ◽  
pp. 102068
Author(s):  
Chen Jin ◽  
Pengfei Wu ◽  
Yushun Yang ◽  
Zhenxiang He ◽  
Hailiang Zhu ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Mei-Ying Huang ◽  
Dian-Wei Wan ◽  
Jie Deng ◽  
Wen-Jie Guo ◽  
Yue Huang ◽  
...  

Background. Activating transcription factor 6 (ATF6) and receptor-interacting protein 3 (RIP3) are important signaling proteins in endoplasmic reticulum (ER) stress and necroptosis, respectively. However, their regulatory relationship and clinical significance are unknown. We investigate the impact of ATF6 on RIP3 expression, and its role in hepatocyte necroptosis in an acute liver injury model. Methods. In vivo and in vitro experiments were carried out. LO2 cells were treated with thapsigargin (TG). In vivo, male BALB/c mice were treated with carbon tetrachloride (CCl4, 1 mL/kg) or tunicamycin (TM, 2 mg/kg). Then, the impact of ATF6 or RIP3 silencing on liver injury, hepatocyte necroptosis, and ER stress-related protein expression was examined. Results. TG induced ER stress and necroptosis and ATF6 and RIP3 expression in LO2 cells. The knockdown of ATF6 significantly decreased RIP3 expression ( p < 0.05 ) and increased ER stress and necroptosis. The downregulation of RIP3 significantly reduced necroptosis and ER stress ( p < 0.05 ). Similar results were observed in CCl4 or the TM-induced mouse model. The knockdown of ATF6 significantly decreased CCl4-induced RIP3 expression and increased liver injury, necroptosis, and ER stress in mice livers ( p < 0.05 ). In contrast, the downregulation of RIP3 significantly reduced liver injury, hepatocyte necroptosis, and ER stress. Conclusions. Hepatocyte ATF6 has multiple roles in acute liver injury. It reduces hepatocyte necroptosis via negative feedback regulation of ER stress. In addition, ATF6 can upregulate the expression of RIP3, which is not helpful to the recovery process. However, downregulating RIP3 reduces hepatocyte necroptosis by promoting the alleviation of ER stress. The findings suggest that RIP3 could be a plausible target for the treatment of liver injury.


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