Life Sciences Commons^™

Integrated Transcriptomics And Histopathology Approach Identifies A Subset Of Rejected Donor Livers With Potential Suitability For Transplantation, Ankita Srivastava, Alexandra Manchel, John Waters, Manju Ambelil, Benjamin K. Barnhart, Jan B. Hoek, Ashesh P. Shah, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Liver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation).

RESULTS: We identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, …

Pathogenesis And Therapeutic Considerations For Nonalcoholic Fatty Liver Disease, Elijah Chung

Senior Honors Theses

A product of the Westernized, high-fat diet, non-alcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease, affecting one-fourth of the world's population. NAFLD is a progressive disease arising from a multisystem response to excess lipids in the blood, adipose tissue, and liver. Despite the prevalence of NAFLD and its well-studied bidirectional association with obesity and type 2 diabetes mellitus and obesity, there is a shocking scarcity of available treatments aside from diet and lifestyle changes. Thus, further research on NAFLD and potential therapies is urgently needed. This paper will illustrate the major pathways associated …

Dataset Of Rna-Seq Transcriptome Of The Fetal Liver At Day 83 Of Gestation Associated With Periconceptual Maternal Nutrition In Beef Heifers, Wellison J.S. Diniz, Alison K. Ward, Kacie L. Mccathy, Cierrah J. Kassetas, Friederike Baumgaertner, Lawrence P. Reynolds, Pawel P. Borowicz, Kevin K. Sedivec, James D. Kirsch, Sheri T. Dorsam, Tammi L. Neville, J. Chris Forcherio, Ronald Scott, Joel S. Caton, Carl R. Dahlen

Department of Animal Science: Faculty Publications

Herein, we present a dataset based on the RNA-Seq analysis of liver tissue from bovine female fetuses at day 83 of gestation. The findings were reported in the main article, “Periconceptual maternal nutrition affects fetal liver programming of energy- and lipid-related genes”[1] . These data were generated to investigate the effects of periconceptual maternal vitamin and mineral supplementation and rates of body weight gain on the transcript abundance of genes associated with fetal hepatic metabolism and function. To this end, crossbred Angus beef heifers ( n = 35) were randomly assigned to 1 of 4 treatments in a 2 × …

Dataset Of Rna-Seq Transcriptome Of The Fetal Liver At Day 83 Of Gestation Associated With Periconceptual Maternal Nutrition In Beef Heifers, Wellison J.S. Diniz, Alison K. Ward, Kacie L. Mccathy, Cierrah J. Kassetas, Friederike Baumgaertner, Lawrence P. Reynolds, Pawel P. Borowicz, Kevin K. Sedivec, James D. Kirsch, Sheri T. Dorsam, Tammi L. Neville, J. Chris Forcherio, Ronald Scott, Joel S. Caton, Carl R. Dahlen

Department of Animal Science: Faculty Publications

Herein, we present a dataset based on the RNA-Seq analysis of liver tissue from bovine female fetuses at day 83 of gestation. The findings were reported in the main article, “Periconceptual maternal nutrition affects fetal liver programming of energy- and lipid-related genes”[1] . These data were generated to investigate the effects of periconceptual maternal vitamin and mineral supplementation and rates of body weight gain on the transcript abundance of genes associated with fetal hepatic metabolism and function. To this end, crossbred Angus beef heifers ( n = 35) were randomly assigned to 1 of 4 treatments in a 2 ×2 …

Beyond The Fat: Protein Metabolism And Muscle Function As Part Of The Migratory Syndrome Of Songbirds, Cory R. Elowe

Doctoral Dissertations

Migration allows animals to seasonally exploit favorable habitats that are geographically disparate, and migratory animals have a suite of adaptations to complete their extraordinary journeys. This “migratory syndrome” of traits is comprised of seasonally-responsive adaptations that together result in changes to metabolism, body composition, and reproductive status, all of which act to increase the probability of a successful migration. The focus of my dissertation is to investigate the suite of changes in metabolism and muscle function that enable birds to undertake long-duration flights. In chapter 1, I compare fuel use in flight between two related migratory warbler species that migrate …

Evaluation Of Feed Additives And Delivery Method For Receiving And Finishing Cattle, Thiago Lauro Maia Ribeiro

Electronic Theses and Dissertations

Trace minerals (TM) and vitamins are essential to improve production output and efficiency in beef cattle. The first experiment was conducted to investigate if the delivery method of TM and Saccharomyces cerevisiae yeast culture influence growth performance and hepatic TM content of receiving steers. The second experiment evaluated the effect of supplemental protected B - vitamins to finishing steers. Experiment 1 used Charolais x Angus steers calves (n = 192; 256 ± 14 kg) in a 49-d receiving experiment. Within 36h of weaning, steers were weighed, allotted to 24 pens (n = 8 steers/pen; 8 pens/treatment) and randomly assigned to …

Hepatotoxic Effect Of Cadmium And Available Therapeutic Options, Tomilola Olaolu, Favour Jibulu, Rotimi Damilare

The Thai Journal of Pharmaceutical Sciences

Hepatoxicity, also known as toxic hepatitis, is a condition, in which the liver becomes inflamed due to exposure to such substances as chemicals, medications, herbal products, or excessive alcohol consumption. Cadmium is a major environmental pollutant from agricultural and industrial sources and has been reported to induce hepatotoxicity. Cadmium can also be found in phosphate fertilizers, detergents, and refined petroleum products as an impurity and used industrially in the production of polyvinyl chloride product stabilizers and the fabrication of nickel-cadmium batteries. Cadmium can be absorbed into the human body through the gastrointestinal tract, respiratory, and dermal routes. Cadmium-induced hepatic damage …

Modulation Of Hepatic Amyloid Precursor Protein And Lipoprotein Receptor-Related Protein 1 By Chronic Alcohol Intake: Potential Link Between Liver Steatosis And Amyloid-Β, Jerome Garcia, Rudy Chang, Ross A. Steinberg, Aldo Arce, Joshua Yang, Peter Van Der Eb, Tamara Abdullah, Devaraj V. Chandrashekar, Syndey M. Eck, Pablo Meza, Zhang-Xu Liu, Enrique Cadenas, David H. Cribbs, Neil Kaplowitz, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Heavy alcohol consumption is a known risk factor for various forms of dementia and the development of Alzheimer’s disease (AD). In this work, we investigated how intragastric alcohol feeding may alter the liver-to-brain axis to induce and/or promote AD pathology. Four weeks of intragastric alcohol feeding to mice, which causes significant fatty liver (steatosis) and liver injury, caused no changes in AD pathology markers in the brain [amyloid precursor protein (APP), presenilin], except for a decrease in microglial cell number in the cortex of the brain. Interestingly, the decline in microglial numbers correlated with serum alanine transaminase (ALT) levels, suggesting …

Intensity-Specific Training Adaptations To Exercise In Females, Julianna P. Mereu

Undergraduate Student Research Internships Conference

Previous studies examining the effects of exercise training on metabolism have primarily used males as participants. It has been shown that as little as one hour of aerobic exercise in males leads to the alteration of several metabolic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphate (G6Pase). Changes in glycogen content and differences in the usage of glycogen for fuel following exercise training have also been shown in male rats. However, it is unclear whether females demonstrate the same training related metabolic adaptations as males.

Therefore, the purpose of this project was to examine various metabolic responses to an acute exercise …

Dysregulation Of Mir-10a Promotes Cancer Features In Cholangiocarcinoma, Matthieu Spriet

Theses & Dissertations

Cholangiocarcinoma is a primary liver cancer of the bile duct epithelium that exhibits microRNA-mediated control of tumor cell signaling. Strides toward new treatment rest on a better defining of cholangiocarcinoma tumor biology including the RNA-based layer of regulation. Additionally, there is a gap in knowledge on microRNA expression in human tissue. While there is RNA-seq data of microRNA expression in tissue, it does not differentiate between cell types, thus leaving unanswered questions about cell specific microRNA biology and expression.

Here, we identify miR-10a as an oncogenic microRNA acting through MAPK signaling. Using cholangiocarcinoma cell lines, we determined miR-10a is an …

Paternal Obesity And Effect Of Fish Oil Supplementation On Offspring Metabolic Health, Akriti Shrestha

Theses - ALL

Obesity and overweight arise due to an abnormal fat accumulation in the body that presents a risk to health. Individuals with body mass index (BMI) of greater than 30 kg/m2 are considered obese. CDC data show that 43% of the adults in the US are obese. The prevalence of obesity as well as its strong association with cardiovascular and metabolic diseases are the serious concerns of public health which calls for the need of appropriate diet/nutrition that can minimize the negative effect of obesity. Literature suggests that 50% of the contribution to obesity can be attributed to genetics. However, studies …

Transcriptomic Analysis Of Liver Indicates Novel Vaccine To Porcine Reproductive And Respiratory Virus Promotes Homeostasis In T-Cell And Inflammatory Immune Responses Compared To A Commercial Vaccine In Pigs, Damarius S. Fleming, Laura C. Miller, Jiuyi Li, Albert Van Geelen, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

One of the largest impediments for commercial swine production is the presence of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a devastating RNA viral infection that is responsible for over $1 billion in loss in the U.S. annually. The challenge with combating PRRSV is a combination of the effect of an extraordinary rate of mutation, the ability to infect macrophages, and subversion of host immune response through a series of actions leading to both immunomodulation and immune evasion. Currently there are a handful of commercial vaccines on the market that have been shown to be effective against homologous infections, but …

Pathological And Immunohistochemical Changes In The Liver Of Monocrotaline-Treated Rats, Şevket Soylu, Aydin Çevi̇k, Necati̇ Ti̇murkaan

Turkish Journal of Veterinary & Animal Sciences

Pathological and immunohistochemical changes in livers were investigated in monocrotaline-treated rats. Eighty adult-male Wistar rats were distributed in 5 groups, each containing 16 animals according to monocrotaline dose (Group I: 50 mg/kg, Group II: 100 mg/kg, Group III: 150 mg/kg, and Group IV: 200 mg/kg). The control group was administered with physiological saline. Half of the animals in each group were euthanized at the 18th hour while the remaining half at the 6th week postinoculation. At the end of the 18th hour, the most prominent lesion was hepatocytic apoptosis which was dose-dependent. Apoptotic cells were mostly located in periportal and …

Monensin Induces Apoptosis In The Liver Tissue And Primary Hepatocytes Of Chicks, Muhammet Yasi̇n Tekeli̇, Murat Kanbur

Turkish Journal of Veterinary & Animal Sciences

In this study, monensin (MON) was investigated for its apoptotic and genotoxic effects on chick liver tissue and cytotoxic and apoptotic effects on chick primary hepatocytes isolated from perfused liver tissue. Western blotting and real-time PCR (qPCR) were used to determine the apoptotic effect on primary hepatocytes and liver tissue, and the comet assay was used to determine the genotoxic effect on liver tissue. MON decreased cell viability in primary hepatocytes with increasing concentrations. When administered at concentrations of 1 and 10 μM, MON increased the levels of apoptotic p53, caspase-3, and caspase-9, and downregulated the expression of the antiapoptotic …

From Cell Death To Regeneration: Rebuilding After Injury, Kelly Tseng, Dylan Guerin, Cindy Kha

Life Sciences Faculty Research

The ability to regrow lost or damaged tissues is widespread, but highly variable among animals. Understanding this variation remains a challenge in regeneration biology. Numerous studies from Hydra to mouse have shown that apoptosis acts as a potent and necessary mechanism in regeneration. Much is known about the involvement of apoptosis during normal development in regulating the number and type of cells in the body. In the context of regeneration, apoptosis also regulates cell number and proliferation in tissue remodeling. Apoptosis acts both early in the process to stimulate regeneration and later to regulate regenerative patterning. Multiple studies indicate that …

Multiwalled Carbon Nanotubes Co-Delivering Sorafenib And Epidermal Growth Factor Receptor Sirna Enhanced Tumor-Suppressing Effect On Liver Cancer., Zhili Wen, Yuliang Feng, Youwen Hu, Lingyan Lian, Hongyan Huang, Li Guo, Shanwen Chen, Qian Yang, Moran Zhang, Lijun Wan, Kedong Xu, Degejirifu, Xiaohua Yan

Faculty Research 2021

OBJECTIVE: This study aimed to investigate the effects of multiwalled carbon nanotubes (MWNTs) co-delivering sorafenib (Sor) and epidermal growth factor receptor (EGFR) siRNA (MWNT/Sor/siRNA) on tumor growth in liver cancer (LC).

RESULTS: MWNT/Sor/siRNA was proved to possess increased Sor release, high siRNA stability, and enhanced cellular uptake. In addition, MWNT treatment has few effects on cell proliferation and apoptosis in HepG2 cells; however, MWNT/Sor/siRNA treatment significantly inhibited clone number and induced cell apoptosis, which shows a more favorable antitumor effect than MWNT/Sor and free Sor and free siRNA in HepG2 cells. Moreover MWNT/Sor/siRNA treatment has the most significant antitumor effect …

In Silico Approach For Hepatoprotective Activity Of Piper Crocatum Leaf Toward Cytochrome P450 2e1 Protein, I. Nyoman Ehrich Lister, Chrismis Novalinda Ginting, Ermi Girsang, Wahyu Widowati, Ika Adhani Sholihah

The Thai Journal of Pharmaceutical Sciences

Liver plays important roles in metabolism of harmful xenobiotics. Prolonged exposure to chemicals, daily dietary supplements, or pharmaceutical drugs may cause liver damage or hepatotoxicity. Acetaminophen is a well-known pharmaceutical drug causing hepatotoxicity through generation of reactive metabolite called N-acetyl-p-benzoquinone imine through Cytochrome P450 2E1 (CYP2E1) metabolism. In the present study, we intended to predict the possible hepatoprotective properties of red betel (Piper crocatum) leaves. Quantitative structure activity relationship (QSAR) was used to predict the antioxidant and anti-inflammatory potential of major compounds of red betel, namely, eugenol, isoeugenol, chavibetol, hydroxychavicol, and allylpyrocatechol. Molecular docking was performed to analyze binding mode …

Lipid Droplet Membrane Proteome Remodeling Parallels Ethanol-Induced Hepatic Steatosis And Its Resolution, Carol A. Casey, Terrence M. Donohue Jr., Jacy L. Kubik, Vikas Kumar, Michael J. Naldrett, Nicholas T. Woods, Cole P. Frisbie, Mark A. Mcniven, Paul G. Thomes

Nebraska Center for Biotechnology: Faculty and Staff Publications

Abstract Lipid droplets (LDs) are composed of neutral lipids enclosed in a phospholipid monolayer, which harbors membrane-associated proteins that regulate LD functions. Despite the crucial role of LDs in lipid metabolism, remodeling of LD protein composition in disease contexts, such as steatosis, remains poorly understood. We hypothesized that chronic ethanol consumption, subsequent abstinence from ethanol, or fasting differentially affects the LD membrane proteome content and that these changes influence how LDs interact with other intracellular organelles. Here, male Wistar rats were pair-fed liquid control or ethanol diets for 6 weeks, and then, randomly chosen animals from both groups were either …

Lipid Metabolites As Energy Stores In Four Stingray Species, Lauren Moniz

Electronic Theses and Dissertations

Assessing macronutrient transfer is important for estimating ecosystem health and structure. This nutrient transfer is facilitated through trophic position interactions and the consumption of biomass. Lipids are macronutrients that can be used to assess energy flow. Triglyceride (TAG) and free fatty acids (FFA) are important lipids that are obtained from diet and integrate into tissues. They are representative of energy stores and potential energy available for metabolic processes. In marine ecosystems, stingrays occupy the mesopredator niche, facilitating nutrient transfer from lower to higher trophic positions. Stingrays consume a variety of prey items ranging in lipid content, but how lipid metabolites …

Ontogeny Related Changes In The Pediatric Liver Metabolome., Christopher M. Wilson, Qian Li, R Gaedigk, Chengpeng Bi, Saskia N. De Wildt, J Steven Leeder, Brooke L. Fridley

Manuscripts, Articles, Book Chapters and Other Papers

Background: A major challenge in implementing personalized medicine in pediatrics is identifying appropriate drug dosages for children. The majority of drug dosing studies have been based on adult populations, often with modification of the dosing for children based on size and weight. However, the growth and development experienced by children between birth and adulthood represents a dynamically changing biological system, with implications for effective drug dosing, efficacy as well as potential drug toxicity. The purpose of this study was to apply a metabolomics approach to gain preliminary insights into the ontogeny of liver function from newborn to adolescent.

Methods: Metabolites …

The Synthesis Of Methotrexate-Loaded F127 Microemulsions And Their In Vivo Toxicity In A Rat Model, Abbas Rahdar, Mohammad Reza Hajinezhad, Sarah Nasri, Hamid Beyzaei, Mahmood Barani, John F. Trant

Chemistry and Biochemistry Publications

Methotrexate (MTX) has been often formulated as nano and micro-emulsions, nominally to address its poor solubility and off-target effects. Nanoformulated MTX is universally reported to be a more efficacious anti-cancer agent than direct-dissolved drug; however, these investigations generally fail to screen for in vivo toxicity. This study aims to remedy this oversight. MTX was formulated as a standard Pluronic oil-in-water microemulsion with good drug encapsulation efficiency (73.0% ± 8.4). Preliminary in vitro free radical scavenging studies found that formulation reduces drug oxidation four-fold. The toxic effects of formulated and unformulated MTX were investigated in a Wistar rat model. Rats received …

Gene Expression Regulation In The Mouse Liver By Mechanistic Target Of Rapamycin Complexes I And Ii, Anthony Poluyanoff

Masters Theses

The mechanistic target of rapamycin (mTOR) is a key serine/threonine protein kinase that functions in complexes mTORC1 and mTORC2. mTORC1, originally discovered due to its sensitivity towards the mTOR inhibitor rapamycin, responds to extracellular growth factor signaling, WNT signaling, and nutrient abundance via glucose and amino acid-triggered signaling. Downstream effectors of mTORC1 include autophagy, mitochondrial metabolic function, protein synthesis, and ribosome biogenesis. mTORC2, initially discovered as a rapamycin-insensitive complex of mTOR, responds to insulin, growth factor signaling, and inflammatory signaling such as tumor necrosis factor-alpha, with its downstream effectors being Akt, a key serine/threonine kinase that functions in cell division …

Food Preservative Sorbic Acid Deregulates Hepatic Fatty Acid Metabolism, Chia-Hui Chen, Sin-Ni Ho, Po-An Hu, Yu Ru Kou, Tzong-Shyuan Lee

Journal of Food and Drug Analysis

Sorbic acid (SA) is one of the most commonly used food preservatives worldwide. Despite SA having no hepatotoxicity at legal dosages, its effect on hepatic lipid metabolism is still unclear. We investigated the effect of SA on hepatic lipid metabolism and its mechanism of action in C57BL/6 mice. Daily treatment with SA (1 g/kg in diet) for 4 weeks did not alter the body weight, organ weight, and blood lipids in mice. However, hepatic lipid accumulation, particularly that of triglycerides, fatty acids, and glycerol, but not cholesteryl ester and free cholesterol, was increased with SA treatment. Mechanistically, SA decreased the …

The Effects Of Retinoic Acid And Insulin On Glycogenesis In Hl1c Hepatoma Cells, Addison J. Bond, Guoxun Chen Dr.

Chancellor’s Honors Program Projects

No abstract provided.

Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation, Ria C. Fyffe-Freil

Theses and Dissertations

Of the over 108,000 American awaiting a life-saving organ transplant today, over 12,000 (11%) of those need a new liver (OPTN, 2020). Last year, only 35% of patients on the waiting list for an organ were transplanted. Improving the quality of marginal organs by preventing or reversing preservation injury could vastly increase the number of transplants performed. Washout of circulating blood during liver procurement with cold University of Wisconsin solution flushes out any endogenous pro-survival signaling molecules. We investigated lysophospholipid (LPL) surface receptors (G-protein coupled receptors for lysophosphatidic acid (LPA) and sphingosine- 1-phosphate (S1P)) and their role in protecting hepatocytes …

Environmental Contaminants, Parasitism, And Neoplasia In White Perch Morone Americana From Chesapeake Bay, Usa, Mark Arnold Matsche

Graduate Theses, Dissertations, and Problem Reports

White perch are an abundant demersal fish species in freshwater and oligohaline habitats of the Chesapeake Bay. An avoidance of salinity > 12-15 ppt generally restricts the distribution and movements of fish to within tributaries in the mid to lower Bay, which over time has resulted in the formation of at least three separate stocks in Chesapeake Bay. Sub-populations of white perch that are partially isolated may serve as sentinels of the conditions or stressors in the tributaries in which they reside. Fish are exposed to a variety of environmental contaminants and other anthropogenic stressors that can vary in magnitude based …

Ultrasonographic Features Of Liver, Gallbladder, Spleen, Kidneys, And Urinary Bladder Ofrescued Long-Tailed Macaques, Macaca Fascicularis, Paul Cardenio, Jezie Acorda, Emilia Lastica-Ternura

Turkish Journal of Veterinary & Animal Sciences

This study was conducted to determine the ultrasonographic features of the liver, gallbladder, spleen, kidneys, and urinary bladder of 24 apparently healthy male and female long-tailed macaques (LTM) and the correlations of organ measurements with body weight and crown?rump length. The animals were grouped into 12 males and 12 females. Examination was performed in sedated LTM using an ultrasound machine with 6.0 MHz microconvex scanner. Ultrasound appearance, dimensions, and echotexture of the liver, gallbladder, kidneys, spleen, and urinary bladder were evaluated. The results showed that there were no sex-related differences in echo mean values, thickness, and length of the selected …

Hepatobiliary Analyses Suggest Chronic Pah Exposure In Hakes (Urophycis Spp.) Following The Deepwater Horizon Oil Spill, Rachel E. Struch, Erin Pulster, Andrea D. Schreier, Steven A. Murawski

C-IMAGE Publications

Prior to the Deepwater Horizon oil spill, we lacked a comprehensive baseline of oil contamination in the Gulf of Mexico's sediments, water column, and biota. Gaps in prespill knowledge limit our ability to determine the aftereffects of the Deepwater Horizon blowout or prepare to mitigate similar impacts during future oil spill disasters. We examined spatiotemporal differences in exposure to and metabolism of polycyclic aromatic hydrocarbons (PAHs) in 2 hake species (Urophycis spp.) to establish a current baseline for these ecologically important, abundant, and at-risk demersal fishes. Gulf hake (Urophycis cirrata) and southern hake (Urophycis floridana) were collected throughout the Gulf …

Effects Of Ivermectin And Perfluorobutanesulfonic Acid (Pfbs) On Lipid Metabolism, Weipeng Qi

Doctoral Dissertations

Accumulating evidence has shown a link between environmental contaminants and altered lipid metabolism. There is currently, however, limited knowledge regarding the causal molecular mechanisms. Therefore, we investigated the molecular mechanisms of two environmental contaminants, ivermectin and perfluorobutanesulfonic acid (PFBS), on lipid metabolism in adipocytes and hepatocytes using cell culture models. We first studied the effects of ivermectin, an anti-parasitic agent, on the adipogenesis of 3T3-L1 preadipocytes. Our current results suggest that ivermectin inhibits adipogenesis in 3T3-L1 preadipocytes and the expression of adipogenic genes where these effects were found to be partially via PPARγ-dependent, but not FXR-dependent, pathway. Additionally, ivermectin also …

Acetaminophen Protein Adducts In Hospitalized Children Receiving Multiple Doses Of Acetaminophen., Sibo Jiang, Valvanera Vozmediano, Susan M. Abdel-Rahman, Stephan Schmidt, Laura P. James

Manuscripts, Articles, Book Chapters and Other Papers

Previous reports have questioned the safety of multiple doses of acetaminophen administered to ill children. Acetaminophen protein adducts (adducts) are a biomarker of acetaminophen-induced liver injury and reflect the oxidative metabolism of acetaminophen, a known mechanism in acetaminophen toxicity. In this prospective observational study, we analyzed adduct concentrations in 1034 blood samples obtained from 181 hospitalized children (1 to 18 years inclusive) who received 2 or more doses of acetaminophen. Linear regression analysis showed that serum adduct concentrations increased as a function of the cumulative acetaminophen dose, which could be attributed, in part, to a long half-life of adducts (2.17 …