Metabolite Profiling of Dihydroartemisinin in Blood of Plasmodium-Infected and Healthy Mice Using UPLC-Q-TOF-MSE
Dihydroartemisinin (DHA) and its’ derivatives have been employed as the most powerful first-line drugs for malarial treatment for several decades. The metabolism of DHA has not been studied clearly. Previous reports were focused on the pharmacokinetics procedure of DHA in healthy rats. The metabolit...
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doaj-45ec9ca35d1e4c309084155e04777a262021-01-18T05:29:55ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-01-011110.3389/fphar.2020.614159614159Metabolite Profiling of Dihydroartemisinin in Blood of Plasmodium-Infected and Healthy Mice Using UPLC-Q-TOF-MSEYifan Zhao0Yifan Zhao1Peng Sun2Peng Sun3Yue Ma4Yue Ma5Xiaoqiang Chang6Xiaoqiang Chang7Xingyu Chen8Xingyu Chen9Xin Ji10Xin Ji11Yue Bai12Yue Bai13Dong Zhang14Dong Zhang15Lan Yang16Lan Yang17Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaArtemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaArtemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaArtemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaArtemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaArtemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaArtemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaArtemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaArtemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, ChinaArtemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, ChinaDihydroartemisinin (DHA) and its’ derivatives have been employed as the most powerful first-line drugs for malarial treatment for several decades. The metabolism of DHA has not been studied clearly. Previous reports were focused on the pharmacokinetics procedure of DHA in healthy rats. The metabolites of DHA in red blood cells (RBC), especially in the RBC from Plasmodium-infected models, have rarely been studied. The Plasmodium species parasitize inside RBC, and these cells should be the final place where DHA performs its activity. In this study, the profile of DHA metabolites in biosample (blood, plasma, and RBC) of the infected and healthy mice was investigated with UPLC-Q-TOF-MS and UNIFI platform to gain insight into DHA metabolism. Results show that a total of 25 metabolites were successfully identified in infected (30 in healthy) blood, 27 in infected (27 in healthy) plasma, and 15 in infected (22 in healthy) RBC. Results show that hydroxylation, OH-dehydration, and glucuronidation reactions were important in the metabolic pathway in vivo. Significantly, DHA metabolites inside RBC were identified for the first time. 8-Hydroxy (8-OH) DHA, 4α-OH deoxy ART, and 6β-OH deoxy ART were identified in vivo for the first time.https://www.frontiersin.org/articles/10.3389/fphar.2020.614159/fulldihydroartemisinin (DHA)metabolite profilingUPLC-ESI-Q-TOF-MSEUNIFI platformPlasmodium berghei ANKAblood |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yifan Zhao Yifan Zhao Peng Sun Peng Sun Yue Ma Yue Ma Xiaoqiang Chang Xiaoqiang Chang Xingyu Chen Xingyu Chen Xin Ji Xin Ji Yue Bai Yue Bai Dong Zhang Dong Zhang Lan Yang Lan Yang |
spellingShingle |
Yifan Zhao Yifan Zhao Peng Sun Peng Sun Yue Ma Yue Ma Xiaoqiang Chang Xiaoqiang Chang Xingyu Chen Xingyu Chen Xin Ji Xin Ji Yue Bai Yue Bai Dong Zhang Dong Zhang Lan Yang Lan Yang Metabolite Profiling of Dihydroartemisinin in Blood of Plasmodium-Infected and Healthy Mice Using UPLC-Q-TOF-MSE Frontiers in Pharmacology dihydroartemisinin (DHA) metabolite profiling UPLC-ESI-Q-TOF-MSE UNIFI platform Plasmodium berghei ANKA blood |
author_facet |
Yifan Zhao Yifan Zhao Peng Sun Peng Sun Yue Ma Yue Ma Xiaoqiang Chang Xiaoqiang Chang Xingyu Chen Xingyu Chen Xin Ji Xin Ji Yue Bai Yue Bai Dong Zhang Dong Zhang Lan Yang Lan Yang |
author_sort |
Yifan Zhao |
title |
Metabolite Profiling of Dihydroartemisinin in Blood of Plasmodium-Infected and Healthy Mice Using UPLC-Q-TOF-MSE |
title_short |
Metabolite Profiling of Dihydroartemisinin in Blood of Plasmodium-Infected and Healthy Mice Using UPLC-Q-TOF-MSE |
title_full |
Metabolite Profiling of Dihydroartemisinin in Blood of Plasmodium-Infected and Healthy Mice Using UPLC-Q-TOF-MSE |
title_fullStr |
Metabolite Profiling of Dihydroartemisinin in Blood of Plasmodium-Infected and Healthy Mice Using UPLC-Q-TOF-MSE |
title_full_unstemmed |
Metabolite Profiling of Dihydroartemisinin in Blood of Plasmodium-Infected and Healthy Mice Using UPLC-Q-TOF-MSE |
title_sort |
metabolite profiling of dihydroartemisinin in blood of plasmodium-infected and healthy mice using uplc-q-tof-mse |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-01-01 |
description |
Dihydroartemisinin (DHA) and its’ derivatives have been employed as the most powerful first-line drugs for malarial treatment for several decades. The metabolism of DHA has not been studied clearly. Previous reports were focused on the pharmacokinetics procedure of DHA in healthy rats. The metabolites of DHA in red blood cells (RBC), especially in the RBC from Plasmodium-infected models, have rarely been studied. The Plasmodium species parasitize inside RBC, and these cells should be the final place where DHA performs its activity. In this study, the profile of DHA metabolites in biosample (blood, plasma, and RBC) of the infected and healthy mice was investigated with UPLC-Q-TOF-MS and UNIFI platform to gain insight into DHA metabolism. Results show that a total of 25 metabolites were successfully identified in infected (30 in healthy) blood, 27 in infected (27 in healthy) plasma, and 15 in infected (22 in healthy) RBC. Results show that hydroxylation, OH-dehydration, and glucuronidation reactions were important in the metabolic pathway in vivo. Significantly, DHA metabolites inside RBC were identified for the first time. 8-Hydroxy (8-OH) DHA, 4α-OH deoxy ART, and 6β-OH deoxy ART were identified in vivo for the first time. |
topic |
dihydroartemisinin (DHA) metabolite profiling UPLC-ESI-Q-TOF-MSE UNIFI platform Plasmodium berghei ANKA blood |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2020.614159/full |
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