Research on the Species Difference of the Hepatotoxicity of Medicine Based on Transcriptome
In recent years, several drugs have been withdrawn from use by regulatory bodies owing to hepatotoxicity; therefore, studies on drug-induced liver injury (DILI) are being actively pursued. Most studies evaluating DILI use rats or mice as animal models to determine drug toxicity; however, the toxicit...
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doaj-3efe029d31774052a108be55f3c732782021-04-23T16:09:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-04-011210.3389/fphar.2021.647084647084Research on the Species Difference of the Hepatotoxicity of Medicine Based on TranscriptomeZiying Xu0Qianjun Kang1Zihui Yu2Zihui Yu3Zihui Yu4Lichun Tian5Jingxuan Zhang6Ting Wang7Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaBeijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaChina National Center for Bioinformation, Beijing, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, ChinaBeijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaBeijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaBeijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaIn recent years, several drugs have been withdrawn from use by regulatory bodies owing to hepatotoxicity; therefore, studies on drug-induced liver injury (DILI) are being actively pursued. Most studies evaluating DILI use rats or mice as animal models to determine drug toxicity; however, the toxicity of a drug can vary between rats or mice. These inconsistencies in in vivo studies among different animal models affect the extrapolation of experimental results to humans. Thus, it is particularly important to choose the most suitable animal model to determine drug hepatotoxicity owing to the genomic differences between rats and mice resulting from evolution. In this study, genome-wide transcriptome analysis was used to explore hepatotoxicity caused by differences in species. Our findings provide the preclinical basis to further study the mechanisms of drug hepatotoxicity and aid in the selection of animal models to determine drug safety. We used murine models (Sprague-Dawley and Wistar rats, ICR and Kunming mice) in this study and by using transcriptome sequencing with the differentially expressed genes in rat and mouse livers as the entry point, we explored the mechanism of oxidative stress and the difference in gene expression in the lipid-metabolism pathway between rats and mice. The clinically established hepatotoxic drugs, fructus psoraleae and acetaminophen were used to validate our study. Using pathological studies, we confirmed that oxidative stress in mice was more serious than that in rats, and that Kunming mice were more suited for the study of oxidative stress-related DILI. The validity of our findings was further verified based on gene expression. Thus, our study could serve as a valuable reference for the evaluation of potential preclinical hepatotoxicity. Moreover, it could be used in the prediction and early diagnosis of drug-induced liver injury caused by traditional Chinese medicine or synthetic drugs, thereby providing a new avenue for drug-toxicity studies.https://www.frontiersin.org/articles/10.3389/fphar.2021.647084/fullhepatotoxicitydrug induced liver injuryspecies differenceoxidative stresssteatosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ziying Xu Qianjun Kang Zihui Yu Zihui Yu Zihui Yu Lichun Tian Jingxuan Zhang Ting Wang |
spellingShingle |
Ziying Xu Qianjun Kang Zihui Yu Zihui Yu Zihui Yu Lichun Tian Jingxuan Zhang Ting Wang Research on the Species Difference of the Hepatotoxicity of Medicine Based on Transcriptome Frontiers in Pharmacology hepatotoxicity drug induced liver injury species difference oxidative stress steatosis |
author_facet |
Ziying Xu Qianjun Kang Zihui Yu Zihui Yu Zihui Yu Lichun Tian Jingxuan Zhang Ting Wang |
author_sort |
Ziying Xu |
title |
Research on the Species Difference of the Hepatotoxicity of Medicine Based on Transcriptome |
title_short |
Research on the Species Difference of the Hepatotoxicity of Medicine Based on Transcriptome |
title_full |
Research on the Species Difference of the Hepatotoxicity of Medicine Based on Transcriptome |
title_fullStr |
Research on the Species Difference of the Hepatotoxicity of Medicine Based on Transcriptome |
title_full_unstemmed |
Research on the Species Difference of the Hepatotoxicity of Medicine Based on Transcriptome |
title_sort |
research on the species difference of the hepatotoxicity of medicine based on transcriptome |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-04-01 |
description |
In recent years, several drugs have been withdrawn from use by regulatory bodies owing to hepatotoxicity; therefore, studies on drug-induced liver injury (DILI) are being actively pursued. Most studies evaluating DILI use rats or mice as animal models to determine drug toxicity; however, the toxicity of a drug can vary between rats or mice. These inconsistencies in in vivo studies among different animal models affect the extrapolation of experimental results to humans. Thus, it is particularly important to choose the most suitable animal model to determine drug hepatotoxicity owing to the genomic differences between rats and mice resulting from evolution. In this study, genome-wide transcriptome analysis was used to explore hepatotoxicity caused by differences in species. Our findings provide the preclinical basis to further study the mechanisms of drug hepatotoxicity and aid in the selection of animal models to determine drug safety. We used murine models (Sprague-Dawley and Wistar rats, ICR and Kunming mice) in this study and by using transcriptome sequencing with the differentially expressed genes in rat and mouse livers as the entry point, we explored the mechanism of oxidative stress and the difference in gene expression in the lipid-metabolism pathway between rats and mice. The clinically established hepatotoxic drugs, fructus psoraleae and acetaminophen were used to validate our study. Using pathological studies, we confirmed that oxidative stress in mice was more serious than that in rats, and that Kunming mice were more suited for the study of oxidative stress-related DILI. The validity of our findings was further verified based on gene expression. Thus, our study could serve as a valuable reference for the evaluation of potential preclinical hepatotoxicity. Moreover, it could be used in the prediction and early diagnosis of drug-induced liver injury caused by traditional Chinese medicine or synthetic drugs, thereby providing a new avenue for drug-toxicity studies. |
topic |
hepatotoxicity drug induced liver injury species difference oxidative stress steatosis |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.647084/full |
work_keys_str_mv |
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