High-mobility group box 1 exacerbates CCl4-induced acute liver injury in mice

2014 ◽  
Vol 153 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Maojian Chen ◽  
Wenjian Huang ◽  
Chao Wang ◽  
Hao Nie ◽  
Gang Li ◽  
...  
Hepatology ◽  
2016 ◽  
Vol 64 (5) ◽  
pp. 1699-1710 ◽  
Author(s):  
Peter Lundbäck ◽  
Jonathan D. Lea ◽  
Agnieszka Sowinska ◽  
Lars Ottosson ◽  
Camilla Melin Fürst ◽  
...  

2021 ◽  
Author(s):  
Zeping Xu ◽  
Xiaofeng Li ◽  
Yuying Li ◽  
Ping Wang ◽  
Junnan Wu ◽  
...  

Abstract Background: Acute liver injury (ALI) involves excessive oxidative stress(OS) and inflammatory responses, leading to a high mortality rate due to lack of effective therapy. Carbon tetrachloride (CCl4) is widely used to induce ALI by induction of reactive oxygen species. Probiotics, including Lactobacillus plantarum ST-III, have been shown to produce antibacterial and antioxidant substances such as organic acids or bacteriocins that reduce liver damage. Nevertheless, the effect of Lactobacillus plantarum ST-III culture supernatant (L-P-cs) on CCl4-induced liver injury remains unclear.Methods: Mice were pretreated with L-P-cs or medium for 14days before one dose of 0.2% CCl4 at 10ml/kg body weight delivered by intraperitoneal injection. CCl4-induced liver injury was examined by measuring serum levels of liver transaminases and high mobility-group box 1 protein (HMGB1) and liver histological staining. Inflammation and apoptosis in liver were evaluated by real-time PCR, enzyme-linked immunosorbent assay (ELISA), and TUNEL staining. Apoptosis in NCTC 1469 cells was detected using CCK8 and western blotting (WB). In liver, OS and endoplasmic reticulum stress(ERS)-related proteins were measured using kits and WB.Results: L-P-cs significantly ameliorated CCl4-induced liver injury and reduced CCl4- induced inflammatory response and apoptosis, consistent with NCTC 1469 cells' results. L-P-cs also restored CCl4-induced increases in cell OS and ERS to normalize liver function. Specifically, L-P-cs pretreatment decreased CCl4-induced increases in nuclear factor (erythroid-2 related) factor 2, HO-1, superoxide dismutase, glucose regulatory protein, and activating transcription factor 6.Conclusion: L-P-cs synergistically improves liver lobule necrosis, hepatocyte inflammation, and apoptosis by reducing liver OS and ERS.


2020 ◽  
Vol 11 ◽  
Author(s):  
Qiushi Xu ◽  
Yunhui Fan ◽  
Juan J. Loor ◽  
Yusheng Liang ◽  
Xudong Sun ◽  
...  

Cardamonin (CD), a naturally occurring chalcone derived from the Alpinia species, has been shown to exert antioxidant and anti-inflammatory activity, but its role in the prevention of acetaminophen- (APAP-) induced hepatotoxicity remains elusive. The objective of this study was to determine the protective effects of CD against APAP-induced acute liver injury (ALI) and the underlying mechanisms. Wild-type or transcription factor nuclear factor erythroid 2-related factor 2- (NFE2L2-) deficient mice were treated with CD (50 or 100 mg/kg, i.p.) or vehicle for 24 h. Subsequently, these mice were challenged with APAP (400 mg/kg, i.p.) for 6 h. Liver and blood samples were collected to evaluate liver injury and protein abundance. Treatment with CD significantly reduced APAP-induced hepatotoxicity. Furthermore, CD effectively reduced APAP-induced inflammation by inhibiting high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), and NOD-like receptor protein 3 (NLRP3) signaling. In addition, CD induced activation of sequestosome 1 (p62) and NFE2L2 signaling and facilitated autophagy. By applying autophagy inhibitor 3-methyladenine (3-MA; 20 mg/kg, i.p.), further mechanistic exploration revealed that NFE2L2 deficiency promoted autophagic activity induced by CD treatment, which was conducive to the hepatoprotective effect of CD against APAP-induced hepatoxicity in NFE2L2−/− mice. Overall, data suggest that CD has hepatoprotective effect against APAP-induced ALI, which might contribute to the activation of NFE2L2 and autophagy.


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