Increasing impact of drug‐induced liver injury

Hayashi, Paul H.; Chalasani, Naga

doi:10.1002/cld.469

Cited by 7 publications

(7 citation statements)

References 8 publications

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“…6−8 The incidence of anthracycline-induced liver injury (AILI) continues to increase as the number of tumor patient survivors increases and higher doses of anthracyclines are administered. 9 AILI is a potentially serious clinical issue and lethal complication. The mechanism of DNRinduced toxicity is reported to be mainly linked to oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

“…Anthracycline, including daunorubicin (DNR) and doxorubicin, an important antitumor drug class, is used to treat various cancers, such as leukemia and solid tumors . However, its application is limited owing to its adverse effects, such as organ toxicity. − The incidence of anthracycline-induced liver injury (AILI) continues to increase as the number of tumor patient survivors increases and higher doses of anthracyclines are administered . AILI is a potentially serious clinical issue and lethal complication.…”

Section: Introductionmentioning

confidence: 99%

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Prussian Blue Nanozymes Prevent Anthracycline-Induced Liver Injury by Attenuating Oxidative Stress and Regulating Inflammation

Bai

Kong

Feng

et al. 2021

ACS Appl. Mater. Interfaces

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Anthracycline-induced liver injury (AILI) is becoming an increasingly serious and potential clinical complication and is linked to reactive oxygen species (ROS) production and subsequent inflammatory response. Herein, we demonstrated that artificial Prussian blue nanozymes (PBZs) prevented daunorubicin-induced liver injury, a prototype of AILI, by attenuating ROS production and regulating inflammation. PBZs exhibited multienzyme activity and could scavenge ROS and free radicals. At the cellular level, PBZs could effectively eliminate ROS, suppress hepatocyte apoptosis, reduce deoxyribonucleic acid damage, and decrease the levels of inflammatory cytokines and chemokines. According to the results of the in vivo study, pretreatment with PBZs also resulted in a desirable protective effect against AILI, as indicated by both a decrease in biochemical indicator levels and hepatocyte necrosis. PBZs upregulated antioxidative genes by activating the Nrf2 pathway to reduce oxidative stress. Meanwhile, PBZs counteracted the inflammatory response based on the decreased expression levels of myeloperoxidase and F4/80 in the liver. Collectively, our findings indicate that PBZ-based nanotherapy is a novel strategy for protecting against AILI.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prussian Blue Nanozymes Prevent Anthracycline-Induced Liver Injury by Attenuating Oxidative Stress and Regulating Inflammation

Bai

Kong

Feng

et al. 2021

ACS Appl. Mater. Interfaces

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“…The true incidence of DILI is difficult to determine due to its lack of standardized diagnostic criteria, delay in diagnosis and unpredictable nature, but the population incidence is likely on the rise. DILI represents a serious clinical problem and potentially fatal course (Hayashi & Chalasani, 2015;Cano-Paniagua et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Identification of exosomal miRNAs associated with the anthracycline-induced liver injury in postoperative breast cancer patients by small RNA sequencing

Zhang

Wang

Shen

et al. 2020

PeerJ

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Background Anthracycline-induced liver injury (AILI) is one of the serious complications of anthracycline-based adjuvant chemotherapy for postoperative breast cancer patients. Exosomal miRNAs, as signaling molecules in intercellular communication, play the essential roles in drug-induced liver injury (DILI). However, the expression profiles of them in patients with AILI remains unknown. Methods Seven post-chemotherapy patients were recruited in this study. After isolated plasma-derived exosomes, small RNA sequencing revealed exosomal miRNA profiles and differentially expressed miRNAs (DE-miRNAs) were identified between the liver injury group and non-liver injury group. miRTarBase and miRDB were used to predict the potential target genes of DE-miRNAs. DILI-related genes were downloaded from the CTD Database. The intersection of predicted genes and DILI-related genes were identified as the AILI-related target genes of the DE-miRNAs. GO annotation and KEGG pathway enrichment analysis were performed by the DAVID database. Furthermore, the protein-protein interaction (PPI) network was established by the STRING database and essential exosomal miRNAs were identified via Cytoscape software. Results A total of 30 DE-miRNAs and 79 AILI-related target genes were identified. AILI-related target genes of the DE-miRNAs are significantly enriched in NOD-like receptor signaling pathway, the HIF-1 signaling pathway, and the FoxO signaling pathway. Then, the hub genes were screened and we discovered that IL-6 and SOD2 are the most critical genes that may be involved in the development of AILI through the activation of immune response and the occurrence of oxidative stress, respectively. In addition, we found that miR-1-3p could potentially regulate most of the hub genes in the miRNA-hub gene network. Conclusion We explored the potential functions of DE-miRNAs and suggested exosomal miR-1-3p might be the essential exosomal miRNA in the pathogenesis of AILI. Moreover, our study provided an experimental basis for experimental verification to reveal the actual function and mechanism of miRNAs in AILI.

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“…The incidence of DILI continues to increase largely due to the exponential growth in the cumulative number of approved clinical medications in recent years. 265 Moreover, the increase in the average life expectancy worldwide is coupled with the growth in the number of individuals with multiple chronic illnesses, who concomitantly use multiple medications. 266,267 This sets up another layer of complexity as the occurrence of DILI is hardly predictable in the presence of multiple xenobiotics given the potential competitive and/or inhibitory effect of each compound on drug-metabolizing enzymes.…”

Section: Drug Metabolism and Pharmacokineticsmentioning

confidence: 99%

Art of Making Artificial Liver: Depicting Human Liver Biology and Diseases in Mice

et al. 2020

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Advancement in both bioengineering and cell biology of the liver led to the establishment of the first-generation humanized liver chimeric mouse (HLCM) model in 2001. The HLCM system was initially developed to satisfy the necessity for a convenient and physiologically representative small animal model for studies of hepatitis B virus and hepatitis C virus infection. Over the last two decades, the HLCM system has substantially evolved in quality, production capacity, and utility, thereby growing its versatility beyond the study of viral hepatitis. Hence, it has been increasingly employed for a variety of applications including, but not limited to, the investigation of drug metabolism and pharmacokinetics and stem cell biology. To date, more than a dozen distinctive HLCM systems have been established, and each model system has similarities as well as unique characteristics, which are often perplexing for end-users. Thus, this review aims to summarize the history, evolution, advantages, and pitfalls of each model system with the goal of providing comprehensive information that is necessary for researchers to implement the ideal HLCM system for their purposes. Furthermore, this review article summarizes the contribution of HLCM and its derivatives to our mechanistic understanding of various human liver diseases, its potential for novel applications, and its current limitations.

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Increasing impact of drug‐induced liver injury

Cited by 7 publications

References 8 publications

Prussian Blue Nanozymes Prevent Anthracycline-Induced Liver Injury by Attenuating Oxidative Stress and Regulating Inflammation

Prussian Blue Nanozymes Prevent Anthracycline-Induced Liver Injury by Attenuating Oxidative Stress and Regulating Inflammation

Identification of exosomal miRNAs associated with the anthracycline-induced liver injury in postoperative breast cancer patients by small RNA sequencing

Art of Making Artificial Liver: Depicting Human Liver Biology and Diseases in Mice

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