PMID- 30405071 OWN - NLM STAT- MEDLINE DCOM- 20190211 LR - 20211204 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 19 IP - 11 DP - 2018 Nov 7 TI - Study on Cardiotoxicity and Mechanism of "Fuzi" Extracts Based on Metabonomics. LID - 10.3390/ijms19113506 [doi] LID - 3506 AB - To investigate the toxicity of water and ethanol "Fuzi" (FZ) extracts and to explore the toxicity mechanism in rats. Water and ethanol extracts were prepared. Three groups of rats received the water extract, ethanol extract, or water by oral gavage for seven days. Pathological section staining of heart tissue. Colorimetric analysis was used to determine serum lactate dehydrogenase. The metabolic expression of small molecules in rats was measured by a metabolomics method. Western blotting was used to detect the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), transforming growth factor-beta1 (TGF-beta1), and caspase-3. Immunohistochemistry was used to detect the expression of CTnI, mTOR, and TGF-beta1. The water and ethanol FZ extracts exert cardiotoxic effects via activating the PI3K/Akt/mTOR signaling pathway to induce cardiomyocyte apoptosis. FAU - Huang, Guangyao AU - Huang G AD - Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China. huangguangyao@stu.ahmu.edu.cn. AD - Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China. huangguangyao@stu.ahmu.edu.cn. FAU - Yang, Liang AU - Yang L AD - Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China. jkliang_yang@126.com. FAU - Zhou, Wei AU - Zhou W AUID- ORCID: 0000-0003-0435-7261 AD - Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China. zhouweisyl802@163.com. FAU - Tang, Xianglin AU - Tang X AD - Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China. tangxianglin@139.com. FAU - Wang, Yuguang AU - Wang Y AD - Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China. wyg79@163.com. FAU - Ma, Zengchun AU - Ma Z AD - Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China. mazchun@139.com. FAU - Gao, Shan AU - Gao S AD - Department of Pharmacology, Basic Medical College, Anhui Medical University, Hefei 230032, China. gaoshan@ahmu.edu.cn. FAU - Gao, Yue AU - Gao Y AD - Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China. gaoyue@nic.bmi.ac.cn. LA - eng GR - 81630102/National Natural Science Foundation of China/ GR - 81673633/National Natural Science Foundation of China/ GR - 81703669/National Natural Science Foundation of China/ GR - 2017ZX09301012-007/National Science and Technology Major Project of China/ PT - Journal Article DEP - 20181107 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Diterpenes) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Plant Extracts) RN - 0 (Transforming Growth Factor beta1) RN - 0 (Troponin I) RN - 0 (fuzi drug herbal) RN - 059QF0KO0R (Water) RN - 3K9958V90M (Ethanol) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Apoptosis MH - Cardiotoxicity/blood/*metabolism/pathology MH - Caspase 3/metabolism MH - Diterpenes MH - Drugs, Chinese Herbal MH - Ethanol MH - Male MH - Metabolome MH - *Metabolomics MH - Myocardium/metabolism/pathology MH - Myocytes, Cardiac/metabolism/pathology MH - Phosphatidylinositol 3-Kinase/metabolism MH - Plant Extracts/*toxicity MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats, Sprague-Dawley MH - Signal Transduction MH - TOR Serine-Threonine Kinases/metabolism MH - Transforming Growth Factor beta1/metabolism MH - Troponin I/metabolism MH - Water PMC - PMC6274692 OTO - NOTNLM OT - Fuzi OT - PI3K/Akt/mTOR OT - cardiotoxicity OT - caspase-3 OT - metabolomics COIS- The authors declare that they have no competing interests to disclose. EDAT- 2018/11/09 06:00 MHDA- 2019/02/12 06:00 PMCR- 2018/11/01 CRDT- 2018/11/09 06:00 PHST- 2018/09/19 00:00 [received] PHST- 2018/10/26 00:00 [revised] PHST- 2018/11/05 00:00 [accepted] PHST- 2018/11/09 06:00 [entrez] PHST- 2018/11/09 06:00 [pubmed] PHST- 2019/02/12 06:00 [medline] PHST- 2018/11/01 00:00 [pmc-release] AID - ijms19113506 [pii] AID - ijms-19-03506 [pii] AID - 10.3390/ijms19113506 [doi] PST - epublish SO - Int J Mol Sci. 2018 Nov 7;19(11):3506. doi: 10.3390/ijms19113506.