Applications in Toxicology & Hepatobiology

App Notes & Tech Briefs

• Screening for Mitochondrial Biogenesis and Toxicity

  A sensitive and robust cell-based screening assay.

  Mitochondrial damage compromises ATP production and consequentially cellular viability. Given the central role that mitochondria play in regulating cellular function, drugs that undermine mitochondrial function frequently elicit toxic effects...

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Publications

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• Mitochondrial Dysfunction Assessed Quantitatively in Real Time by Measuring the Extracellular Flux of Oxygen and Protons

  Ferrick D, Wu M, Swift A L and Neilson A

  Drug-Induced Mitochondrial Dysfunction; 2008 Jan 22. :Ch 14.

• In vitro assessment of mitochondrial dysfunction and cytotoxicity of nefazodone, trazodone, and buspirone

  Dykens J A, Jamieson J D, Marroquin L D, Nadanaciva S, Xu J J, Dunn M C, Smith A R and Will Y

  Toxicol Sci; 2008 Jun 1. 103 (2):335-345.

• Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro

  Dykens J A, Jamieson J, Marroquin L, Nadanaciva S, Billis P A and Will Y

  Toxicol Appl Pharmacol; 2008 Dec 1. 233 (2):203-210.

• The role of CYP3A4 in amiodarone-associated toxicity on HepG2 cells

  Zahno A, Brecht K, Morand R, Maseneni S, Torok M, Lindinger P W and Krahenbuhl S

  Biochem Pharmacol; 2011 Feb 1. 81 (3):432-441.

• Metabolic profiles show specific mitochondrial toxicities in vitro in myotube cells

  Xu Q, Vu H, Liu L, Wang T C and Schaefer W H

  J Biomol NMR; 2011 Apr 1. 49 (4-Mar):207-219.

• Molecular imaging of intracellular drug-membrane aggregate formation

  Baik J and Rosania G R

  Mol Pharm; 2011 Oct 3. 8 (5):1742-1749.

• Mitochondrial development of the in vitro hepatic organogenesis model with simultaneous cardiac mesoderm differentiation from murine induced pluripotent stem cells

  Tamai M, Yamashita A and Tagawa Y I

  J Biosci Bioeng; 2011 Nov 1. 112 (5):495-500.

• Susceptibility to simvastatin-induced toxicity is partly determined by mitochondrial respiration and phosphorylation state of Akt

  Mullen P J, Zahno A, Lindinger P, Maseneni S, Felser A, Krahenbuhl S and Brecht K

  Biochim Biophys Acta; 2011 Dec 1. 1813 (12):2079-87.

• Nitric oxide and hypoxia exacerbate alcohol-induced mitochondrial dysfunction in hepatocytes

  Zelickson B R, Benavides G A, Johnson M S, Chacko B K, Venkatraman A, Landar A, Betancourt A M, Bailey S M and Darley-Usmar V M

  Biochim Biophys Acta; 2011 Dec 1. 1807 (12):1573-82.

• Gene-dose influences cellular and calcium channel dysregulation in heterozygous and homozygous T4826I-RYR1 malignant hyperthermia susceptible muscle

  Barrientos G C, Feng W, Truong K, Matthaei K I, Yang T, Allen P D, Lopez J R and Pessah I N

  J Biol Chem; 2012 Jan 20. 287 (4):2863-76.

• The impact of assay technology as applied to safety assessment in reducing compound attrition in drug discovery

  Thomas C E and Will Y

  Expert Opinion on Drug Discovery; 2012 Feb 1. 7 (2):109-122.

• Ethanol Suppresses Ureagenesis in Rat Hepatocytes: Role of Acetaldehyde

  Holmuhamedov E L, Czerny C, Beeson C C and Lemasters J J

  J Biol Chem; 2012 Mar 2. 287 (10):7692-700.

• Hemin causes mitochondrial dysfunction in endothelial cells through promoting lipid peroxidation: The protective role of autophagy

  Higdon A N, Benavides G A, Chacko B K, Ouyang X, Johnson M S, Landar A, Zhang J and Darley-Usmar V M

  Am J Physiol Heart Circ Physiol; 2012 Apr 1. 302 (7):H1394-409.

• Caveolin-1 orchestrates the balance between glucose and lipid-dependent energy metabolism: implications for liver regeneration

  Fernandez-Rojo M A, Restall C, Ferguson C, Martel N, Martin S, Bosch M, Kassan A, Leong G M, Martin S D, McGee S L, Muscat G E, Anderson R L, Enrich C, Pol A and Parton R G

  Hepatology; 2012 May 1. 55 (5):1574-84.

• Additive effects of mitochondria-targeted Cytochrome P4502E1 and alcohol toxicity on cytochrome c oxidase function and the stability of respirosome complexes

  Bansal S, Srinivasan S, Anandasadagopan S, Roy Chowdhury A, Selvaraj V, Kalyanaraman B, Joseph J and Avadhani N G

  J Biol Chem; 2012 May 4. 287 (19):15284-97.

• Additive Effects of Mitochondrion-targeted Cytochrome CYP2E1 and Alcohol Toxicity on Cytochrome c Oxidase Function and Stability of Respirosome Complexes

  Bansal S, Srinivasan S, Anandasadagopan S, Roy Chowdhury A, Selvaraj V, Kalyanaraman B, Joseph J and Avadhani N G

  J Biol Chem; 2012 May 4. 287 (19):15284-15297.

• Molecular Analysis of Mitochondrial Compromise in Rodent Cardiomyocytes Exposed Long Term to Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

  Liu Y, Nguyen P, Baris T Z and Poirier M C

  Cardiovasc Toxicol; 2012 Jun 1. 12 (2):123-34.

• Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells

  Luo Y, Rana P and Will Y

  Toxicol Appl Pharmacol; 2012 Jun 1. 261 (2):172-80.

• BNip3 regulates mitochondrial function and lipid metabolism in the liver.

  Glick D, Zhang W, Beaton M, Marsboom G, Gruber M, Simon M C, Hart J, Dorn G W, 2nd, Brady M J and Macleod K F

  Mol Cell Biol; 2012 Jul 1. 32 (13):2570-84.

• Assessment of drug-induced mitochondrial dysfunction via altered cellular respiration and acidification measured in a 96-well platform

  Nadanaciva S, Rana P, Beeson G C, Chen D, Ferrick D A, Beeson C C and Will Y

  J Bioenerg Biomembr; 2012 Aug 1. 44 (4):421-37.

• Overexpression of Endothelial Nitric Oxide Synthase Prevents Diet-Induced Obesity and Regulates Adipocyte Phenotype

  Sansbury B E, Cummins T D, Tang Y, Hellmann J, Holden C R, Harbeson M A, Chen Y, Patel R P, Spite M R, Bhatnagar A and Hill B G

  Circ Res; 2012 Oct 12. 111 (9):1176-89.

• Mitochondrial bioenergetics and drug-induced toxicity in a panel of mouse embryonic fibroblasts with mitochondrial DNA single nucleotide polymorphisms

  Pereira C V, Oliveira P J, Will Y and Nadanaciva S

  Toxicol Appl Pharmacol; 2012 Oct 15. 264 (2):167-81.

• Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages

  Jantzen K, Roursgaard M, Desler C, Loft S, Rasmussen L J and Moller P

  Mutagenesis; 2012 Nov 1. 27 (6):693-701.

• Characterization of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes: Bioenergetics and Utilization in Safety Screening

  Rana P, Anson B, Engle S and Will Y

  Toxicol Sci; 2012 Nov 1. 130 (1):117-31.

• An indole-derivative protects against acetaminophen-induced liver injury by directly binding to N-acetyl-p-benzoquinone imine in mice

  Park J H, Seo K S, Tadi S, Ahn B H, Lee J U, Heo J Y, Han J, Song M S, Kim S H, Yim Y H, Choi H S, Shong M and Kweon G R

  Antioxid Redox Signal. 2012 Nov 2; [Epub ahead of print].

• Disordered purinergic signaling and abnormal cellular metabolism are associated with development of liver cancer in Cd39/Entpd1 null mice

  Sun X, Han L, Seth P, Bian S, Li L, Csizmadia E, Junger W G, Schmelzle M, Usheva A, Tapper E B, Baffy G, Sukhatme V P, Wu Y and Robson S C

  Hepatology; 2013 Jan 1. 57 (1):205-16.

• Mechanisms of hepatocellular toxicity associated with dronedarone--a comparison to amiodarone

  Felser A, Blum K, Lindinger P W, Bouitbir J and Krahenbuhl S

  Toxicol Sci; 2013 Feb 1. 131 (2):480-490.

• Amphiphilic silver-delaminated clay nanohybrids and their composites with polyurethane: physico-chemical and biological evaluations

  Chi T-Y, Yeh H-Y, Lin J-J, Jeng U S and Hsu S-h

  J Mater Chem B; 2013 Mar 11. 1 (16):2178-2189.

• Licochalcone A regulates hepatic lipid metabolism through activation of AMP-activated protein kinase

  Quan H Y, Kim S J, Kim D Y, Jo H K, Kim G W and Chung S H

  Fitoterapia. 2013 Mar 14; [Epub ahead of print].

• Metabolic effects of TiO2 nanoparticles, a common component of sunscreens and cosmetics, on human keratinocytes

  Tucci P, Porta G, Agostini M, Dinsdale D, Iavicoli I, Cain K, Finazzi-Agro A, Melino G and Willis A

  Cell Death Dis; 2013 Mar 21. 4:e549.

• Identification of the molecular basis of doxorubicin-induced cardiotoxicity

  Zhang S, Liu X, Bawa-Khalfe T, Lu L S, Lyu Y L, Liu L F and Yeh E T

  Nature medicine; 2013 Nov 1. 18 (11):1639-1642.

Technical Posters

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• Striatal synaptosome mitochondrial function is not altered following a 6mo MeHg treatment in male BALB/c mice

  Sara M. Fox and William D. Atchison

  Society of Toxicology 2013
  March 10-14, 2013
  San Antonio, TX

• An in vitro framework to investigate mitochondrial idiosyncratic drug-responses in a panel of genetically diverse mouse embryonic fibroblasts

  Claudia V. Pereira, Paulo J. Oliveira, Yvonne Will, Sashi Nadanaciva

  European Bioenergetic Conference (EBEC 2012)
  September 15-20, 2012
  Freiberg, DE

• Effect of mitochondrial ATP binding cassette transporter B6 (ABCB6) in arsenic toxicity and mitochondrial function

  Hemantkumar Chavan, Jianghua Lu, Russell Swerdlow and Partha Krishnamurthy

  Society for Toxicology 2012 Annual Meeting
  March 11-15, 2012
  San Francisco, CA

• Chronic ethanol consumption increases the sensitivity of hepatocyte mitochondria to NO-dependent bioenergetic dysfunction.

  Gloria A. Benavides, Blake R. Zelickson, Michelle S. Johnson, Balu K. Chacko, Aimee Landar, Victor Darley-Usmar

  Society for Free Radical Biology and Medicine (SFRBM) 2011
  November 16-20, 2011
  Atlanta, GA

• Assessment of mitochondrial dysfunction and cytotoxicity of bisphenol A in isolated hepatocytes

  Angela M. Betancourt and Shannon M. Bailey

  Society for Free Radical Biology and Medicine (SFRBM) 2011
  November 16-20, 2011
  Atlanta, GA

• Abrupt Alcohol Withdrawal suppresses Mitochondrial Repiration in an Estrogen Preventable Manner

  Xiaohua Ju, Daniel Metzger, Yi Wen, Shaohua Yang, James W. Simpkins and Marianna Jung

  Neuroscience 2010
  November 13-17, 2010
  San Diego, CA, US

• Simvastatin: The Enemy Within?

  PJ Mullen, A Zahno, S Maseneni, S Krahensbuhl, P Lindinger

  European Muscle Conference, XXXIX
  September 14, 2010
  Padua, IT

• In vitro detection of pharmaceutical compounds that disturb mitochondrial functions

  Irene Edebert, Ingalill Rafter, Ian Cotgreave

  46th Congress of the European Societies of Toxicology
  September 13-16, 2009
  Dresden, Germany

Webinars

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• 

  Using Reserve Capacity to Screen for Mitochondrial Toxicities and Biogenesis

  Craig C. Beeson, PhD, Medical University of South Carolina
  March 23, 2011

• 

  Primary Renal Proximal Tubules as a Platform for Mitochondrial Biogenesis and Toxicity Assays

  Craig Beeson, PhD , Medical University of South Carolina
  June 24, 2009

• 

  Fluorescent Reporters of Mitochondrial Function in the Life and Death of Cells

  John J. LeMasters, MD, PhD, Medical University of South Carolina
  February 18, 2009

• 

  Achieving Higher Throughput and Greater Content When Measuring Mitochondrial Function

  David Ferrick, PhD, CSO, Seahorse Bioscience
  January 22, 2009

• 

  Mitochondrial Toxicity: Designing Novel Screening Methods to Reduce NCE Attrition

  Yvonne Will, PhD, Cell Based Assays, Pfizer
  September 24, 2008

• 

  Tutorial: Measuring Bioenergetics in a Variety of Cell Types

  David Ferrick, PhD, CSO, Seahorse Bioscience
  July 17, 2008

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