Article
Toxicology
Nga T. Nguyen, Jephte Y. Akakpo, James L. Weemhoff, Anup Ramachandran, Wen-Xing Ding, Hartmut Jaeschke
Summary: Acetaminophen is a commonly used analgesic, but overdose can be hepatotoxic. This study investigated liver injury after multiple subtoxic doses and the role of autophagy in responding to this regimen.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Plant Sciences
Gislane dos Santos Ribeiro, Diegue Henrique Nascimento Martins, Joao Victor Dutra Gomes, Noel William Davies, Christopher William Fagg, Luiz Alberto Simeoni, Mauricio Homem-de-Mello, Perola Oliveira Magalhaes, Damaris Silveira, Yris Maria Fonseca-Bazzo
Summary: This study investigated the protective effects of four Cerrado plant species against acetaminophen toxicity in HepG2 cells. The results showed that the extracts could provide cell protection and did not increase the toxic effect of acetaminophen. This protection may be attributed to antioxidant compounds present in the extracts.
Article
Nutrition & Dietetics
Zhixiang Xu, Yue Jia, Jun Liu, Xiaomin Ren, Xiaoxia Yang, Xueshan Xia, Xuejun Pan
Summary: This study aimed to investigate the synergistic antitumor effects of tamoxifen and naringenin/quercetin on human hepatic carcinoma, and to explore the potential molecular mechanisms involved. The results demonstrated that a combination of tamoxifen and higher concentrations of naringenin or quercetin significantly inhibited cell growth and migration, stimulated apoptosis, and resulted in loss of mitochondrial membrane potential. These effects were regulated by ROS-mediated p53 signaling cascades. On the other hand, lower concentrations of naringenin and quercetin regulated cell migration, invasion, cycle, and apoptosis, thereby inhibiting the tamoxifen-induced antiproliferative effects.
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
Food Science & Technology
Sreelekshmi Mohan, Genu George, K. G. Raghu
Summary: The study found that vanillic acid has potential nutraceutical effects by reducing oxidative stress and lipid peroxidation, protecting mitochondria, and preventing glycation during hyperinsulinemia. It acts through the AMPK/Sirt1/PGC-1 alpha pathway to achieve its beneficial activities.
Article
Food Science & Technology
Enrique Garcia-Perez, Dojin Ryu, Chan Lee, Hyun Jung Lee
Summary: Ochratoxin A (OTA) is a mycotoxin found in foods that can cause oxidative stress, leading to cytotoxicity in HepG2 cells, including an increase in ROS and a depletion of GSH. Additionally, OTA downregulates the mRNA level of catalase (CAT) and decreases CAT enzymatic activity in a dose-dependent manner.
Article
Engineering, Environmental
Tin Yan Wong, Neng Yan, Kenneth Kin Leung Kwan, Yanrong Pan, Jingjing Liu, Yao Xiao, Long Wu, Henry Lam
Summary: Silver nanoparticles (AgNPs) have raised concerns due to their potential harmful effects on human beings. This study investigated the hepatotoxic effects of AgNPs using a comparative proteomics approach. The results showed that cancerous liver cells and normal cells respond to AgNPs exposure through different pathways, providing new insights into mechanisms underlying AgNPs-induced hepatotoxicity.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Review
Pharmacology & Pharmacy
Hartmut Jaeschke, Olamide B. Adelusi, Jephte Y. Akakpo, Nga T. Nguyen, Giselle Sanchez-Guerrero, David S. Umbaugh, Wen-Xing Ding, Anup Ramachandran
Summary: The APAP model is used to study drug-induced liver injury mechanisms and test potential therapeutic interventions. A thorough understanding of the pathophysiology is required to obtain valid results and clinically relevant information. Key factors to consider when studying APAP hepatotoxicity include drug metabolism, mitochondrial dysfunction, necrotic cell death, autophagy, and sterile inflammatory response.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Biochemistry & Molecular Biology
Yanqi Lin, Xiaowen Wu, Lingli Lin, Yuanyuan Mei, Jing Zhou, Chaoxiang Chen, Jian Li, Daren Wu, Jingwen Liu, Guiling Li
Summary: This study found that EPA can upregulate miR-494-5p to regulate cellular oxidative stress and enhance antioxidant capacity. miR-494-5p inhibits the expression of MIEF1 gene, leading to the modulation of mitochondrial structure and activity, thus improving cellular antioxidant capacity. This study provides novel insights into the post-translational regulation of antioxidation reactions involving mitochondria.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Food Science & Technology
Julia Beisl, Gudrun Pahlke, Monika Ehling-Schulz, Giorgia Del Favero, Doris Marko
Summary: Food contaminants of bacterial or fungal origin frequently contaminate staple foods. The toxins CER and DON are commonly found in these foods and can be absorbed by the human body, causing mitochondrial and lysosomal toxicity. The study suggests that CER induces autophagy through the LC3 pathway, leading to the elimination of damaged mitochondria.
Article
Pharmacology & Pharmacy
Fang Liu, Yan Liu, Qifeng Peng, Guodong Wang, Qing Tan, Zhongyue Ou, Qishan Xu, Chixiang Liu, Daming Zuo, Jianbo Zhao
Summary: This study revealed that creatinine is closely related to drug-induced liver injury and exacerbates APAP-induced hepatocyte death by promoting the production and activation of reactive oxygen species and c-Jun N-terminal kinase.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maud Maillard, Cecile Arellano, Christelle Vachoux, Christine Chevreau, Nicolas J. Cabaton, Frederic Pont, Nathalie Saint-Laurent, Thierry Lafont, Etienne Chatelut, Fabienne Thomas
Summary: This study found that the aldehyde derivatives of tyrosine kinase inhibitors pazopanib and sunitinib, P-CHO and S-CHO, affect hepatocyte integrity and may be involved in their hepatotoxicity.
Article
Pharmacology & Pharmacy
Yanying Zhou, Xiaomei Fan, Tingying Jiao, Wenzhou Li, Panpan Chen, Yiming Jiang, Jiahong Sun, Yixin Chen, Pan Chen, Lihuan Guan, Yajie Wen, Min Huang, Huichang Bi
Summary: SIRT6 plays a protective role in APAP-induced liver injury by alleviating oxidative stress and promoting hepatocyte proliferation. In addition, SIRT6 also exerts important regulatory functions by interacting with NRF2 and P53.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Plant Sciences
Zixia Hu, Yanjia Zhao, Yi Yang, Wei Li, Rong Tan, Linhua Zhao, Xiaolin Tong, Ying Peng, Jiang Zheng
Summary: In this study, a mechanism-based biomarker based on plasma protein adduction was developed to determine the exposure to Dioscorea bulbifera L. (DBL) and predict DBL-induced hepatotoxicity. The results showed that the adduction of DBL metabolite to plasma proteins correlated well with the exposure of DBL in rats, making it a potential biomarker for diagnosing DBL-induced liver injury and an indicator for DBL medication plans.
Article
Agriculture, Multidisciplinary
Chunjing Guan, Guode Zhao, Chen Sun, Mingyu Zhang, Siyu Liu, Ziying Jiang, Weiwei Li, Ying Peng, Jiang Zheng
Summary: This study aims to characterize the reactive metabolites of IPC in vitro and in vivo, identify the cytochrome P450 enzymes responsible for metabolic activation, and determine the correlation between metabolic activation and cytotoxicity of IPC. Results showed that GSH and NAC conjugates were detected after IPC exposure in GSH- or NAC-supplemented microsomal incubations. These conjugates were also found in mouse liver homogenates and urine after IPC administration. IPC was found to be metabolized to a quinone intermediate reactive to GSH, and it induced cytotoxicity in cultured mouse primary hepatocytes. The cytotoxicity was attenuated by the selective CYP3A4/5 enzyme inhibitor, ketoconazole.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Editorial Material
Medical Laboratory Technology
Mitchell R. McGill, Ann M. Gronowski
CLINICAL CHEMISTRY
(2018)
Article
Food Science & Technology
Andrew J. Lutkewitte, George G. Schweitzer, Stefanie Kennon-McGill, Melissa M. Clemens, Laura P. James, Hartmut Jaeschke, Brian N. Finck, Mitchell R. McGill
FOOD AND CHEMICAL TOXICOLOGY
(2018)
Article
Toxicology
Steven R. McGreal, Bharat Bhushan, Chad Walesky, Mitchell R. McGill, Margitta Lebofsky, Sylvie E. Kandel, Robert D. Winefield, Hartmut Jaeschke, Natasha E. Zachara, Zhen Zhang, Ee Phie Tan, Chad Slawson, Udayan Apte
TOXICOLOGICAL SCIENCES
(2018)
Letter
Toxicology
Mitchell R. McGill
TOXICOLOGICAL SCIENCES
(2018)
Review
Biochemistry & Molecular Biology
Mitchell R. McGill, Hartmut Jaeschke
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2019)
Article
Pathology
Mitchell R. McGill, Hartmut Jaeschke
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2018)
Article
Pharmacology & Pharmacy
Joshua L. Kennedy, Richard C. Kurten, Sandra McCullough, Reynold A. Panettieri, Cynthia Koziol-White, Stacie M. Jones, Katherine Caid, Pritmohinder S. Gill, Dean Roberts, Hartmut Jaeschke, Mitchell R. McGill, Laura James
Article
Food Science & Technology
Melissa M. Clemens, Stefanie Kennon-McGill, Udayan Apte, Laura P. James, Brian N. Finck, Mitchell R. McGill
FOOD AND CHEMICAL TOXICOLOGY
(2019)
Article
Toxicology
Ryan C. Kennedy, Andrew K. Smith, Glen E. P. Ropella, Mitchell R. McGill, Hartmut Jaeschke, C. Anthony Hunt
TOXICOLOGICAL SCIENCES
(2019)
Article
Biochemistry & Molecular Biology
Laura E. Ewing, Charles M. Skinner, Charles M. Quick, Stefanie Kennon-McGill, Mitchell R. McGill, Larry A. Walker, Mahmoud A. ElSohly, Bill J. Gurley, Igor Koturbash
Article
Nutrition & Dietetics
Bill J. Gurley, Isabelle R. Miousse, Intawat Nookaew, Laura E. Ewing, Charles M. Skinner, Piroon Jenjaroenpun, Thidathip Wongsurawat, Stefanie Kennon-McGill, Bharathi Avula, Ji-Yeong Bae, Mitchell R. McGill, David Ussery, Ikhlas A. Khan, Igor Koturbash
Article
Pharmacology & Pharmacy
Michael D. Hambuchen, Michael D. Berquist, Christy M. Simecka, Mitchell R. McGill, Melinda G. Gunnell, Howard P. Hendrickson, S. Michael Owens
JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
(2019)
Article
Biochemistry & Molecular Biology
Laura E. Ewing, Mitchell R. McGill, Eric U. Yee, Charles M. Quick, Charles M. Skinner, Stefanie Kennon-McGill, Melissa Clemens, Joel H. Vazquez, Sandra S. McCullough, D. Keith Williams, Kristy R. Kutanzi, Larry A. Walker, Mahmoud A. ElSohly, Laura P. James, Bill J. Gurley, Igor Koturbash
Article
Audiology & Speech-Language Pathology
Stefanie Kennon-McGill, Melissa M. Clemens, Mitchell R. McGill
Article
Toxicology
Joel H. Vazquez, Melissa M. Clemens, Felicia D. Allard, Eric U. Yee, Stefanie Kennon-McGill, Samuel G. Mackintosh, Hartmut Jaeschke, Michael D. Hambuchen, Mitchell R. McGill
TOXICOLOGICAL SCIENCES
(2020)
