Article
Pharmacology & Pharmacy
Yiwei Zhu, Lin Lei, Xinghui Wang, Linfang Chen, Wei Li, Jinxia Li, Chenchen Zhao, Xiliang Du, Yuxiang Song, Wenwen Gao, Guowen Liu, Xinwei Li
Summary: This study investigates the role of NEDD4-1 in the pathogenesis of acetaminophen-induced liver injury (AILI). The results demonstrate that NEDD4-1 acts as a suppressor of AILI by regulating the degradation of VDAC1.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Biochemistry & Molecular Biology
Jing Li, Xuewen Tang, Xing Wen, Xiaoyuan Ren, Huihui Zhang, Yatao Du, Jun Lu
Summary: Acetaminophen overdose is a common cause of drug-induced liver injury. The reaction between APAP metabolite and thiol molecules is the main cause of APAP-induced hepatotoxicity, but the role of other thiol-related regulators is unclear. In this study, the deletion of the Glrx2 gene worsened APAP-induced liver damage by interrupting the thiol-redox compensatory response and enhancing the AIF pathway-mediated oxidative damage.
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
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
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
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
Y. Li, M. Gao, L. -H. Yin, L. -N. Xu, Y. Qi, Pengyuan Sun, J. -Y. Peng
Summary: Dioscin can alleviate MTX-induced hepatorenal damages by regulating oxidative stress mediated by miR-145-5p. This natural product may be considered as an effective drug for treating this disorder in the future.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Jaewon Lee, Jihoon Ha, Jun-Hyeong Kim, Dongyeob Seo, Minbeom Kim, Yerin Lee, Seong Shil Park, Dahee Choi, Jin Seok Park, Young Jae Lee, Siyoung Yang, Kyung-Min Yang, Su Myung Jung, Suntaek Hong, Seung-Hoi Koo, Yong-Soo Bae, Seong-Jin Kim, Seok Hee Park
Summary: A study has shown that the enzyme Pellino3 plays a critical role in triggering liver damage caused by acetaminophen. Mice lacking Pellino3 showed reduced liver damage, suggesting that drugs targeting Pellino3 activation could help protect the liver from APAP-induced injury.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
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
Toxicology
David S. Umbaugh, Nga T. Nguyen, Hartmut Jaeschke, Anup Ramachandran
Summary: Mitochondrial morphology changes play a critical role in acetaminophen (APAP) hepatotoxicity, with distinct morphologies corresponding to differences in mitochondrial respiratory function and polarization. These changes in morphology are dose-dependent and can be reversible or irreversible depending on the severity of APAP overdose.
TOXICOLOGICAL SCIENCES
(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)
Article
Pharmacology & Pharmacy
Mohamed E. Shaker, Hesham A. M. Gomaa, Sara H. Hazem, Mohamed A. Abdelgawad, Mohamed El-Mesery, Ahmed A. Shaaban
Summary: The study investigated the role of PI3K alpha in hepatic sterile inflammation caused by APAP-overdose and found that the selective modulation of PI3K alpha activity by alpelisib can inhibit the inflammatory response and immune cell infiltration. Alpelisib reduced the escalation of liver function biomarkers and hepatic necroinflammation score, as well as apoptosis and proliferation in liver hepatocytes induced by APAP. It also limited the overproduction of pro-inflammatory cytokines and the activation of several signal transduction proteins.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Materials Science, Biomaterials
Chongqing Chen, Haitao Wu, Qianhui Li, Menghua Liu, Fan Yin, Miaomiao Wu, Xiaoli Wei, Hua Wang, Zhengbao Zha, Fei Wang
Summary: As one of the leading cases of acute liver failure triggered by excessive Acetaminophen (APAP), the mechanisms of APAP-induced liver injury (AILI) involve breakdown of the antioxidant system, inflammatory response, and apoptosis due to the overaccumulation of reactive oxygen species (ROS). To prevent the overproduction of ROS, manganese Prussian blue nanozymes (MPBZs) with superior antioxidant enzyme-like activity are used for hepatocyte protection. These MPBZs accumulate in the liver and scavenge excess ROS, thus alleviating oxidative stress and mediating various biological signaling pathways for enhanced tolerance against AILI.
BIOMATERIALS SCIENCE
(2023)
Article
Medicine, Research & Experimental
Xue-Liang Dang, Long-Fei Yang, Lei Shi, Long-Fei Li, Ping He, Jie Chen, Bei-Jie Zheng, Peng Yang, Ai-Dong Wen
Summary: The study indicates that post-treatment with glycyrrhizin can dose-dependently attenuate hepatic mitochondrial damage and inhibit the up-regulation of hepatic nNOS induced by APAP. Glycyrrhizin shows promise as a drug for the treatment of APAP hepatotoxicity.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2021)
