TY - JOUR
T1 - Asking the right questions with animal models
T2 - Methionine- and choline-deficient model in predicting adverse drug reactions in human NASH
AU - Li, Hui
AU - Toth, Erica
AU - Cherrington, Nathan J.
N1 - Publisher Copyright:
© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
PY - 2018/1
Y1 - 2018/1
N2 - 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 in humans. Extrapolating animal data to accurately predict human toxicities remains a challenge, and researchers are obligated to question the appropriateness of their chosen animal model. This paper provides an assessment of the utility of the methionine- and choline-deficient (MCD) diet fed animal model in reflecting human nonalcoholic steatohepatitis (NASH) and the potential risks of adverse drug reactions and toxicities that are associated with the disease. As a commonly used NASH model, the MCD model fails to exhibit most metabolic abnormalities in a similar manner to the human disease. The MCD model, on the other hand, closely resembles human NASH histology and reflects signatures of drug transporter alterations in humans. Due to the nature of the MCD model, it should be avoided in studies of NASH pathogenesis, metabolic parameter evaluation, and biomarker identification. But it can be used to accurately predict altered drug disposition due to NASH-associated transporter alterations.
AB - 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 in humans. Extrapolating animal data to accurately predict human toxicities remains a challenge, and researchers are obligated to question the appropriateness of their chosen animal model. This paper provides an assessment of the utility of the methionine- and choline-deficient (MCD) diet fed animal model in reflecting human nonalcoholic steatohepatitis (NASH) and the potential risks of adverse drug reactions and toxicities that are associated with the disease. As a commonly used NASH model, the MCD model fails to exhibit most metabolic abnormalities in a similar manner to the human disease. The MCD model, on the other hand, closely resembles human NASH histology and reflects signatures of drug transporter alterations in humans. Due to the nature of the MCD model, it should be avoided in studies of NASH pathogenesis, metabolic parameter evaluation, and biomarker identification. But it can be used to accurately predict altered drug disposition due to NASH-associated transporter alterations.
KW - Adverse drug reactions
KW - Animal models
KW - MCD model
KW - NASH
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U2 - 10.1093/toxsci/kfx253
DO - 10.1093/toxsci/kfx253
M3 - Review article
C2 - 29145614
AN - SCOPUS:85039857459
SN - 1096-6080
VL - 161
SP - 23
EP - 33
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 1
ER -