Article
Pharmacology & Pharmacy
Wen Su, Mingji Feng, Yuan Liu, Rong Cao, Yiao Liu, Junyao Tang, Ke Pan, Rongfeng Lan, Zhuo Mao
Summary: Deficiency of ZnT8 in mice alleviates APAP-induced liver injury by inhibiting oxidative stress and promoting hepatocyte proliferation.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Linlin Qu, Rongzhan Fu, Xiaoxuan Ma, Daidi Fan
Summary: Ginsenoside Rk3 shows promising therapeutic potential in protecting against APAP-induced acute liver injury by reducing hepatotoxicity, inhibiting liver inflammation and oxidative stress, and promoting continuous activation of autophagy.
Article
Biochemistry & Molecular Biology
Anup Ramachandran, Hartmut Jaeschke
Summary: Despite extensive research on APAP hepatotoxicity over almost 50 years, recent progress has been made in understanding the involvement of oxidative and nitrosative stress in the pathophysiology, as well as the accurate reflection of liver injury mechanisms in animals to humans. Future directions include refining the mechanistic understanding of APAP hepatotoxicity, identifying additional drugs to prevent cell death, and exploring mechanisms of regeneration and drug development to promote recovery.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Biology
Zhao Shan, Leike Li, Constance Lynn Atkins, Meng Wang, Yankai Wen, Jongmin Jeong, Nicolas F. Moreno, Dechun Feng, Xun Gui, Ningyan Zhang, Chun Geun Lee, Jack A. Elias, William M. Lee, Bin Gao, Fong Wilson Lam, Zhiqiang An, Cynthia Ju
Summary: The study uncovered the critical role of Chi3I1 in mediating APAP-induced hepatic platelet recruitment, signaling through CD44 and C-type lectin-like receptor 2. Inhibiting Chi3I1 effectively attenuated liver injury induced by APAP.
Article
Cell Biology
Zhiyuan Fang, Yanyong Xu, Guowen Liu, Qi Shao, Xiaodi Niu, Wenjun Tai, Taiyu Shen, Minghe Fan, Meng Chen, Lin Lei, Wenwen Gao, Yuxiang Song, Zhe Wang, Xiliang Du, Xinwei Li
Summary: The main bioactive constituents in citrus peels, narirutin (NR), can alleviate APAP-induced liver injury by activating a PPP3/calcineurin-TFEB-ALP axis, suggesting its potential as a treatment for APAP overdose.
Article
Immunology
Hao Wu, Chunqing Guo, Zheng Liu, Jinyang Cai, Chong Wang, Huanfa Yi, Arun Sanyal, Puneet Puri, Huiping Zhou, Xiang-Yang Wang
Summary: Drug-associated hepatotoxicity, particularly acetaminophen-induced liver injury (AILI), is a major cause of acute liver failure. This study reveals that serum levels of the pro-inflammatory cytokine interferon (IFN)- γ correlate with disease severity in patients with drug hepatotoxicity. The researchers found that hepatic neutrophils are the primary source of IFN- γ production in response to APAP-injured hepatocytes, and inhibition of IFN- γ effectively reduces hepatotoxicity.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Gastroenterology & Hepatology
Zhenzhen Sun, Qian Wang, Le Sun, Mengying Wu, Shuzhen Li, Hu Hua, Ying Sun, Tong Ni, Chunlei Zhou, Songming Huang, Aihua Zhang, Yue Zhang, Zhanjun Jia
Summary: This study revealed the important role of NEK7 in acetaminophen-induced acute liver injury. Reduced NEK7 exacerbates liver damage and provides protection against APAP-induced injury by regulating the cell cycle progression.
Article
Biochemistry & Molecular Biology
Yuguo Yi, Weigao Zhang, Liang Tao, Qianchao Shao, Qian Xu, Yuxin Chen, Haibing Zhang, Jianfa Zhang, Dan Weng
Summary: This study investigated the role of RIP1 kinase in APAP-induced acute liver injury through genetic or pharmacological inhibition, providing evidence that RIP1 kinase activity plays an important role in the pathogenesis of APAP-induced liver injury. The results demonstrated that RIP1 kinase inactivation significantly attenuated APAP-induced liver injury and mortality, and that Nec-1, a RIP1 kinase inhibitor formulated with PEG400, could efficiently alleviate hepatotoxicity induced by APAP.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Cell Biology
Xin Hou, Qi Liu, Yimin Gao, Liang Yong, Huiyuan Xie, Wenting Li, Yuping Zhou, Jun Liu, Lijie Feng, Long Xu, Yuxian Shen, Hua Wang
Summary: The levels of mesencephalic astrocyte-derived neurotrophic factor (MANF) were found to be elevated in drug-induced liver injury, and MANF plays an important role in immune regulation and liver repair. MANF may enhance IL-10 expression and phagocytosis in macrophages via the p38 MAPK pathway, promoting the phenotype conversion of inflammatory macrophages to pro-restorative macrophages.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Chen Zhang, Xiao Shi, Zhongping Su, Chao Hu, Xianmin Mu, Jinshun Pan, Mengjing Li, Fengmeng Teng, Tao Ling, Ting Zhao, Che Xu, Guozhong Ji, Qiang You
Summary: The study demonstrated that CD36 deficiency ameliorated APAP-induced acute liver injury and inflammatory responses by decreasing JNK activation. CD36 might serve as a new target to reduce acute liver injury.
MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Jinke Zhang, Mengcheng Li, Tianrui Zhao, Jianxin Cao, Yaping Liu, Yongpeng Wang, Yifen Wang, Guiguang Cheng
Summary: This study found that E Se tea, enriched in dihydrochalcones, has a protective effect on acetaminophen-induced acute liver injury by reducing inflammation and oxidative stress, and upregulating antioxidant genes.
Article
Cell Biology
Mingzhu Yan, Chong Zhao, Shangyun Lu, Jinling Cui, Zhenou Sun, Xiaoyi Liu, Shuo Liu, Yazhen Huo, Shutao Yin, Hongbo Hu
Summary: TMAO exacerbates APAP-induced liver toxicity by hindering macrophage-mediated liver repair, possibly stemming from the inhibition of Mmp12. Liver damage in patients with high circulating TMAO levels may be more severe in AILI, caution should be exercised in treatment.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Cell Biology
Mengjing Li, Tao Ling, Fengmeng Teng, Chao Hu, Zhongping Su, Chen Zhang, Xiang Li, Ting Zhao, Xianmin Mu, Yingchang Li, Jinshun Pan, Qiang You
Summary: CD5 molecule like (CD5L) is increased in mouse livers following acetaminophen (APAP) overdose, and CD5L deficiency can mitigate APAP-induced liver injury. This suggests that CD5L may be a potential therapeutic target for the prevention and treatment of APAP hepatotoxicity.
CELL DEATH DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Jae Ho Choi, Sun Woo Jin, Gi Ho Lee, Eun Hee Han, Yong Pil Hwang, Hye Gwang Jeong
Summary: Rutaecarpine shows protective effects against acetaminophen-induced liver toxicity by reducing liver damage indicators, inhibiting inflammatory cytokine expression, and enhancing antioxidant enzyme activity, indicating its great therapeutic potential in treating liver injury.
Review
Pharmacology & Pharmacy
Anna Licata, Maria Giovanna Minissale, Simona Stankeviciute, Judith Sanabria-Cabrera, Maria Isabel Lucena, Raul J. Andrade, Piero Luigi Almasio
Summary: N-acetylcysteine (NAC) is an effective therapeutic option for acetaminophen (APAP) overdose, improving hepatotoxicity and reducing mortality. The timing of treatment initiation, within 8 to 24 hours after APAP overdose, is crucial for preventing or minimizing liver damage.
FRONTIERS IN PHARMACOLOGY
(2022)