Full Text Journal Articles by
Author Nathan J Cherrington

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Multiple Computational Approaches for Predicting Drug Interactions with Human Equilibrative Nucleoside Transporter 1.

Siennah R Miller, Thomas R Lane, Kimberley M Zorn, Sean Ekins, Stephen H Wright, Nathan J Cherrington,

Equilibrativenucleoside transporters (ENTs) participate in the pharmacokinetics and disposition of nucleoside analog drugs. Understanding drug interactions with the ENTs may inform and facilitate the development of new drugs, including chemotherapeutics and antivirals that require access to sanctuary sites such as the male genital tract. This study created three-dimensional pharmacophores for ... Read more >>

Drug Metab Dispos (Drug metabolism and disposition: the biological fate of chemicals)
[2021, 49(7):479-489]

Cited: 1 time

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Implications of Species Differences in Function and Localization of Transporters at the Blood-Testis Barrier.

Raymond K Hau, Siennah R Miller, Nathan J Cherrington,

Toxicol Sci (Toxicological sciences : an official journal of the Society of Toxicology)
[2021, 181(1):1-2]

Cited: 0 times

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Predicting Drug Interactions with Human Equilibrative Nucleoside Transporters 1 and 2 Using Functional Knockout Cell Lines and Bayesian Modeling.

Siennah R Miller, Xiaohong Zhang, Raymond K Hau, Joseph L Jilek, Erin Q Jennings, James J Galligan, Daniel H Foil, Kimberley M Zorn, Sean Ekins, Stephen H Wright, Nathan J Cherrington,

Equilibrative nucleoside transporters (ENTs) 1 and 2 facilitate nucleoside transport across the blood-testis barrier (BTB). Improving drug entry into the testes with drugs that use endogenous transport pathways may lead to more effective treatments for diseases within the reproductive tract. In this study, CRISPR/CRISPR-associated protein 9 was used to generate ... Read more >>

Mol Pharmacol (Molecular pharmacology)
[2021, 99(2):147-162]

Cited: 2 times

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Generation of a hTERT-Immortalized Human Sertoli Cell Model to Study Transporter Dynamics at the Blood-Testis Barrier.

Raymond K Hau, Siennah R Miller, Stephen H Wright, Nathan J Cherrington,

The blood-testis barrier (BTB) formed by adjacent Sertoli cells (SCs) limits the entry of many chemicals into seminiferous tubules. Differences in rodent and human substrate-transporter selectivity or kinetics can misrepresent conclusions drawn using rodent in vitro models. Therefore, human in vitro models are preferable when studying transporter dynamics at the ... Read more >>

Pharmaceutics (Pharmaceutics)
[2020, 12(11):]

Cited: 1 time

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Folate receptor-beta expression as a diagnostic target in human & rodent nonalcoholic steatohepatitis.

April D Lake, Rhiannon N Hardwick, Christopher P Leamon, Philip S Low, Nathan J Cherrington,

<h4>Introduction</h4>Nonalcoholic steatohepatitis (NASH) afflicts 20-36% of individuals with nonalcoholic fatty liver disease (NAFLD). A lipotoxic hepatic environment, altered innate immune signaling and inflammation are defining features of progression to NASH. Activated resident liver macrophages express folate receptor beta (FR-β) which may be an indicator of progression from steatosis to NASH. ... Read more >>

Toxicol Appl Pharmacol (Toxicology and applied pharmacology)
[2019, 368:49-54]

Cited: 1 time

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Alcohol Metabolism in the Progression of Human Nonalcoholic Steatohepatitis.

Hui Li, Erica Toth, Nathan J Cherrington,

Alcohol metabolism is a well-characterized biological process that is dominated by the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) families. Nonalcoholic steatohepatitis (NASH) is the advanced inflammatory stage of nonalcoholic fatty liver disease (NAFLD) and is known to alter the metabolism and disposition of numerous drugs. The purpose of this ... Read more >>

Toxicol Sci (Toxicological sciences : an official journal of the Society of Toxicology)
[2018, 164(2):428-438]

Cited: 6 times

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Asking the Right Questions With Animal Models: Methionine- and Choline-Deficient Model in Predicting Adverse Drug Reactions in Human NASH.

Hui Li, Erica Toth, Nathan J Cherrington,

In the past few decades, great conceptual and technological advances have been made in the field of toxicology, but animal model-based research still remains one of the most widely used and readily available tools for furthering our current knowledge. However, animal models are not perfect in predicting all systemic toxicity ... Read more >>

Toxicol Sci (Toxicological sciences : an official journal of the Society of Toxicology)
[2018, 161(1):23-33]

Cited: 6 times

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Misregulation of membrane trafficking processes in human nonalcoholic steatohepatitis.

Anika L Dzierlenga, Nathan J Cherrington,

Nonalcoholic steatohepatitis (NASH) remodels the expression and function of genes and proteins that are critical for drug disposition. This study sought to determine whether disruption of membrane protein trafficking pathways in human NASH contributes to altered localization of multidrug resistance-associated protein 2 (MRP2). A comprehensive immunoblot analysis assessed the phosphorylation, ... Read more >>

J Biochem Mol Toxicol (Journal of biochemical and molecular toxicology)
[2018, 32(3):e22035]

Cited: 2 times

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Pediatric Cytochrome P450 Activity Alterations in Nonalcoholic Steatohepatitis.

Hui Li, Mark J Canet, John D Clarke, Dean Billheimer, Stavra A Xanthakos, Joel E Lavine, Robert P Erickson, Nathan J Cherrington,

Variable drug responses depend on individual variation in the activity of drug-metabolizing enzymes, including cytochrome P450 enzymes (CYP). As the most common chronic liver disease in children and adults, nonalcoholic steatohepatitis (NASH) has been identified as a source of significant interindividual variation in hepatic drug metabolism. Compared with adults, children ... Read more >>

Drug Metab Dispos (Drug metabolism and disposition: the biological fate of chemicals)
[2017, 45(12):1317-1325]

Cited: 6 times

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Metabolomic profiling distinction of human nonalcoholic fatty liver disease progression from a common rat model.

JianHua Han, Anika L Dzierlenga, Zhengqiang Lu, Dean D Billheimer, Elmira Torabzadeh, April D Lake, Hui Li, Petr Novak, Petia Shipkova, Nelly Aranibar, Donald Robertson, Michael D Reily, Lois D Lehman-McKeeman, Nathan J Cherrington,

<h4>Objective</h4>Characteristic pathological changes define the progression of steatosis to nonalcoholic steatohepatitis (NASH) and are correlated to metabolic pathways. A common rodent model of NASH is the methionine and choline deficient (MCD) diet. The objective of this study was to perform full metabolomic analyses on liver samples to determine which pathways ... Read more >>

Obesity (Silver Spring) (Obesity (Silver Spring, Md.))
[2017, 25(6):1069-1076]

Cited: 21 times

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Dysregulated expression of proteins associated with ER stress, autophagy and apoptosis in tissues from nonalcoholic fatty liver disease.

Seungwoo Lee, Soohee Kim, Seungwoo Hwang, Nathan J Cherrington, Doug-Young Ryu,

Nonalcoholic fatty liver disease (NAFLD) is categorized into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) and has emerged as a risk factor for more critical clinical conditions. However, the underlying mechanisms of NAFLD pathogenesis are not fully understood. In this study, expression of proteins associated with endoplasmic reticulum (ER) ... Read more >>

Oncotarget (Oncotarget)
[2017, 8(38):63370-63381]

Cited: 25 times

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Regulation of drug metabolism and toxicity by multiple factors of genetics, epigenetics, lncRNAs, gut microbiota, and diseases: a meeting report of the 21st International Symposium on Microsomes and Drug Oxidations (MDO).

Ai-Ming Yu, Magnus Ingelman-Sundberg, Nathan J Cherrington, Lauren M Aleksunes, Ulrich M Zanger, Wen Xie, Hyunyoung Jeong, Edward T Morgan, Peter J Turnbaugh, Curtis D Klaassen, Aadra P Bhatt, Matthew R Redinbo, Pengying Hao, David J Waxman, Li Wang, Xiao-Bo Zhong,

Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21<sup>st</sup> International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2-6, 2016, a number of speakers reported some new ... Read more >>

Acta Pharm Sin B (Acta pharmaceutica Sinica. B)
[2017, 7(2):241-248]

Cited: 9 times

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Impaired N-linked glycosylation of uptake and efflux transporters in human non-alcoholic fatty liver disease.

John D Clarke, Petr Novak, April D Lake, Rhiannon N Hardwick, Nathan J Cherrington,

<h4>Background & aims</h4>N-linked glycosylation of proteins is critical for proper protein folding and trafficking to the plasma membrane. Drug transporters are one class of proteins that have reduced function when glycosylation is impaired. N-linked glycosylation of plasma proteins has also been investigated as a biomarker for several liver diseases, including ... Read more >>

Liver Int (Liver international : official journal of the International Association for the Study of the Liver)
[2017, 37(7):1074-1081]

Cited: 23 times

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Localization of nucleoside transporters in rat epididymis.

David M Klein, Marcus C Harding, Meghan K Crowther, Nathan J Cherrington,

The epididymis relies on transporters for the secretion of nucleosides and influence the disposition of nucleoside analogs (NSA). Since these compounds can cross the blood-testis barrier (BTB), it is important to understand if the epididymis reabsorbs NSA drugs. The purpose of this study is to determine the localization of nucleoside ... Read more >>

J Biochem Mol Toxicol (Journal of biochemical and molecular toxicology)
[2017, 31(8):]

Cited: 3 times

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Transcription factor binding site enrichment analysis predicts drivers of altered gene expression in nonalcoholic steatohepatitis.

April D Lake, Alexandria L Chaput, Petr Novak, Nathan J Cherrington, Catharine L Smith,

The molecular mechanisms behind the transition from simple steatosis to nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease (NAFLD) are not clearly understood. This hinders development of effective therapies for treatment and prevention of NASH. In this study expression profiling data from normal, steatosis, and NASH human livers were used ... Read more >>

Biochem Pharmacol (Biochemical pharmacology)
[2016, 122:62-71]

Cited: 7 times

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Effect of nonalcoholic steatohepatitis on renal filtration and secretion of adefovir.

Tomas Laho, John D Clarke, Anika L Dzierlenga, Hui Li, David M Klein, Michael Goedken, Stanislav Micuda, Nathan J Cherrington,

<h4>Background and aims</h4>Adefovir, an acyclic nucleotide reverse transcriptase inhibitor used to treat hepatitis B viral infection, is primarily eliminated renally through cooperation of glomerular filtration with active tubular transport. Nonalcoholic steatohepatitis is a variable in drug disposition, yet the impact on renal transport processes has yet to be fully understood. ... Read more >>

Biochem Pharmacol (Biochemical pharmacology)
[2016, 115:144-151]

Cited: 1 time

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Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease.

Eric J Ditzel, Hui Li, Caroline E Foy, Alec B Perrera, Patricia Parker, Benjamin J Renquist, Nathan J Cherrington, Todd D Camenisch,

Non-alcoholic fatty liver disease can result in changes to drug metabolism and disposition potentiating adverse drug reactions. Furthermore, arsenite exposure during development compounds the severity of diet-induced fatty liver disease. This study examines the effects of arsenite potentiated diet-induced fatty liver disease on hepatic transport in male mice. Changes were ... Read more >>

J Biochem Mol Toxicol (Journal of biochemical and molecular toxicology)
[2016, 30(7):321-330]

Cited: 5 times

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Hepatic Transporter Expression in Metabolic Syndrome: Phenotype, Serum Metabolic Hormones, and Transcription Factor Expression.

Ajay C Donepudi, Qiuqiong Cheng, Zhenqiang James Lu, Nathan J Cherrington, Angela L Slitt,

Metabolic syndrome is a multifactorial disease associated with obesity, insulin resistance, diabetes, and the alteration of multiple metabolic hormones. Obesity rates have been rising worldwide, which increases our need to understand how this population will respond to drugs and exposure to other chemicals. The purpose of this study was to ... Read more >>

Drug Metab Dispos (Drug metabolism and disposition: the biological fate of chemicals)
[2016, 44(4):518-526]

Cited: 5 times

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Mechanism of Altered Metformin Distribution in Nonalcoholic Steatohepatitis.

John D Clarke, Anika L Dzierlenga, Nicholas R Nelson, Hui Li, Samantha Werts, Michael J Goedken, Nathan J Cherrington,

Metformin is an antihyperglycemic drug that is widely prescribed for type 2 diabetes mellitus and is currently being investigated for the treatment of nonalcoholic steatohepatitis (NASH). NASH is known to alter hepatic membrane transporter expression and drug disposition similarly in humans and rodent models of NASH. Metformin is almost exclusively ... Read more >>

Diabetes (Diabetes)
[2015, 64(9):3305-3313]

Cited: 15 times

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Mechanistic basis of altered morphine disposition in nonalcoholic steatohepatitis.

Anika L Dzierlenga, John D Clarke, Tiffanie L Hargraves, Garrett R Ainslie, Todd W Vanderah, Mary F Paine, Nathan J Cherrington,

Morphine is metabolized in humans to morphine-3-glucuronide (M3G) and the pharmacologically active morphine-6-glucuronide (M6G). The hepatobiliary disposition of both metabolites relies upon multidrug resistance-associated proteins Mrp3 and Mrp2, located on the sinusoidal and canalicular membrane, respectively. Nonalcoholic steatohepatitis (NASH), the severe stage of nonalcoholic fatty liver disease, alters xenobiotic metabolizing ... Read more >>

J Pharmacol Exp Ther (The Journal of pharmacology and experimental therapeutics)
[2015, 352(3):462-470]

Cited: 27 times

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Nonalcoholic steatohepatitis in precision medicine: Unraveling the factors that contribute to individual variability.

John D Clarke, Nathan J Cherrington,

There are numerous factors in individual variability that make the development and implementation of precision medicine a challenge in the clinic. One of the main goals of precision medicine is to identify the correct dose for each individual in order to maximize therapeutic effect and minimize the occurrence of adverse ... Read more >>

Pharmacol Ther (Pharmacology & therapeutics)
[2015, 151:99-106]

Cited: 10 times

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Branched chain amino acid metabolism profiles in progressive human nonalcoholic fatty liver disease.

April D Lake, Petr Novak, Petia Shipkova, Nelly Aranibar, Donald G Robertson, Michael D Reily, Lois D Lehman-McKeeman, Richard R Vaillancourt, Nathan J Cherrington,

Nonalcoholic fatty liver disease (NAFLD) is a globally widespread disease of increasing clinical significance. The pathological progression of the disease from simple steatosis to nonalcoholic steatohepatitis (NASH) has been well defined, however, the contribution of altered branched chain amino acid metabolomic profiles to the progression of NAFLD is not known. ... Read more >>

Amino Acids (Amino acids)
[2015, 47(3):603-615]

Cited: 62 times

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Renal xenobiotic transporter expression is altered in multiple experimental models of nonalcoholic steatohepatitis.

Mark J Canet, Rhiannon N Hardwick, April D Lake, Anika L Dzierlenga, John D Clarke, Michael J Goedken, Nathan J Cherrington,

Nonalcoholic fatty liver disease is the most common chronic liver disease, which can progress to nonalcoholic steatohepatitis (NASH). Previous investigations demonstrated alterations in the expression and activity of hepatic drug transporters in NASH. Moreover, studies using rodent models of cholestasis suggest that compensatory changes in kidney transporter expression occur to ... Read more >>

Drug Metab Dispos (Drug metabolism and disposition: the biological fate of chemicals)
[2015, 43(2):266-272]

Cited: 8 times

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Systems level metabolic phenotype of methotrexate administration in the context of non-alcoholic steatohepatitis in the rat.

Michael Kyriakides, Rhiannon N Hardwick, Zhaosheng Jin, Michael J Goedken, Elaine Holmes, Nathan J Cherrington, Muireann Coen,

Adverse drug reactions (ADRs) represent a significant clinical challenge with respect to patient morbidity and mortality. We investigated the hepatotoxicity and systems level metabolic phenotype of methotrexate (MTX) in the context of a prevalent liver disease; non-alcoholic steatohepatitis (NASH). A nuclear magnetic resonance spectroscopic-based metabonomic approach was employed to analyze ... Read more >>

Toxicol Sci (Toxicological sciences : an official journal of the Society of Toxicology)
[2014, 142(1):105-116]

Cited: 5 times

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Identification of a functional antioxidant response element within the eighth intron of the human ABCC3 gene.

Mark J Canet, Matthew D Merrell, Bryan G Harder, Jonathan M Maher, Tongde Wu, Andrew J Lickteig, Jonathan P Jackson, Donna D Zhang, Masayuki Yamamoto, Nathan J Cherrington,

The ATP-binding cassette (ABC) family of transporters, including ABCC3, is a large family of efflux pumps that plays a pivotal role in the elimination of xenobiotics from the body. ABCC3 has been reported to be induced during hepatic stress conditions and through the progression of some forms of cancer. Several ... Read more >>

Drug Metab Dispos (Drug metabolism and disposition: the biological fate of chemicals)
[2015, 43(1):93-99]

Cited: 13 times

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