Indoleamine 2, 3-dioxygenase 1 aggravates acetaminophen-induced acute liver failure by triggering excess nitroxidative stress and iron accumulation
| Autor: | Menghan Yang, Shu Xu, Shuoyi Ma, Chaofeng Wu, Yunqing Wang, Qinxiang Tan, Jun Ma, Mu-keng Hong, Yunjia Li, Hao Shi, Yanhong Zhang, Ming Wang, Yuhong Song, Lei Gao, Haixin Ye, Huacong Huang, Juan Li, Yuyao Chen, Guanghui Deng, Zhiyun Zeng |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Iron Transferrin receptor medicine.disease_cause Biochemistry Dioxygenases Lipid peroxidation chemistry.chemical_compound Mice Physiology (medical) Internal medicine medicine Animals Indoleamine 2 3-dioxygenase Reactive nitrogen species Acetaminophen Liver injury chemistry.chemical_classification digestive oral and skin physiology Liver Failure Acute medicine.disease Mice Inbred C57BL Oxidative Stress Endocrinology chemistry Liver Transferrin Hepatocytes Chemical and Drug Induced Liver Injury Oxidative stress medicine.drug |
| Zdroj: | Free radical biologymedicine. 172 |
| ISSN: | 1873-4596 |
| Popis: | Acetaminophen (APAP) is the leading cause of acute liver failure (ALF), which is characterized by GSH depletion, oxidative stress and mitochondrial dysfunction. However, the specific mechanism of APAP-induced ALF remains to be clarified. In this study, we demonstrated that indoleamine 2,3-dioxygenase 1 (IDO1) aggravated APAP-induced ALF associated with excess lipid peroxidation, which was reversed by lipid peroxidation inhibitor (ferrostatin-1). Meanwhile, IDO1 deficiency effectively decreased the accumulation of reactive nitrogen species. Additionally, IDO1 deficiency prevented against APAP-induced liver injury through suppressing the activation of macrophages, thereby reduced their iron uptake and export, eventually reduced iron accumulation in hepatocytes through transferrin and transferrin receptor axis. In summary, our study confirmed that APAP-induced IDO1 aggravated ALF by triggering excess oxidative and nitrative stress and iron accumulation in liver. These results offer new insights for the clinical treatment of ALF or iron-dysregulated liver diseases in the future. |
| Databáze: | OpenAIRE |
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