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Long-Term Exposure of Psoralen and Isopsoralen Induced Hepatotoxicity and Serum Metabolites Profiles Changes in Female Rats

by Yingli Yu 1,2,†, Pengli Wang 1,3,†, Ruili Yu 1, Jiaxi Lu 1,3, Miaomiao Jiang 1,3,* and Kun Zhou 1,2,*
1
Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
2
Tianjin Key Laboratory of Chinese medicine Pharmacology, Tianjin 300193, China
3
Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin 300193, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Metabolites 2019, 9(11), 263; https://doi.org/10.3390/metabo9110263
Received: 29 August 2019 / Revised: 30 October 2019 / Accepted: 31 October 2019 / Published: 2 November 2019
Pre-clinical safety evaluation of traditional medicines is imperative because of the universality of drug-induced adverse reactions. Psoralen and isopsoralen are the major active molecules and quality-control components of a traditional herbal medicine which is popularly used in Asia, Fructus Psoraleae. The purpose of this study is to assess the long-term effects of psoralen and isopsoralen with low levels on the biochemical parameters and metabolic profiles of rats. Three doses (14, 28, and 56 mg/kg) of psoralen and one dose (28 mg/kg) of isopsoralen were administered to rats over 12 weeks. Blood and selected tissue samples were collected and analyzed for hematology, serum biochemistry, and histopathology. Metabolic changes in serum samples were detected via proton nuclear magnetic resonance (1H-NMR) spectroscopy. We found that psoralen significantly changed the visceral coefficients, blood biochemical parameters, and histopathology, and isopsoralen extra influenced the hematological index. Moreover, psoralen induced remarkable elevations of forvaline, isoleucine, isobutyrate, alanine, acetone, pyruvate, glutamine, citrate, unsaturated lipids, choline, creatine, phenylalanine, and 4-hydroxybenzoate, and significant reductions of ethanol and dimethyl sulfone. Isopsoralen only induced a few remarkable changes of metabolites. These results suggest that chronic exposure to low-level of psoralen causes a disturbance in alanine metabolism, glutamate metabolism, urea cycle, glucose-alanine cycle, ammonia recycling, glycine, and serine metabolism pathways. Psoralen and isopsoralen showed different toxicity characteristics to the rats. View Full-Text
Keywords: Fructus Psoraleae; psoralen; isopsoralen; sd rats; toxicity; metabolomics Fructus Psoraleae; psoralen; isopsoralen; sd rats; toxicity; metabolomics
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Yu, Y.; Wang, P.; Yu, R.; Lu, J.; Jiang, M.; Zhou, K. Long-Term Exposure of Psoralen and Isopsoralen Induced Hepatotoxicity and Serum Metabolites Profiles Changes in Female Rats. Metabolites 2019, 9, 263.

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