Subchronic toxicological study of two artemisinin derivatives in dogs.
The objective of our study was to profile and compare the systematic changes between orally administered artesunate and intramuscularly injected artemether at a low dose over a 3-month period (92 consecutive days) in dogs. Intramuscular administration of 6 mg kg-1 artemether induced a decreased red...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3989207?pdf=render |
| _version_ | 1811197868150620160 |
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| author | Ji-ye Yin He-mei Wang Quan-jun Wang Yan-sheng Dong Gang Han Yong-biao Guan Ke-yong Zhao Wen-sheng Qu Ye Yuan Xiao-xin Gao Shu-fang Jing Ri-gao Ding |
| author_facet | Ji-ye Yin He-mei Wang Quan-jun Wang Yan-sheng Dong Gang Han Yong-biao Guan Ke-yong Zhao Wen-sheng Qu Ye Yuan Xiao-xin Gao Shu-fang Jing Ri-gao Ding |
| author_sort | Ji-ye Yin |
| collection | DOAJ |
| description | The objective of our study was to profile and compare the systematic changes between orally administered artesunate and intramuscularly injected artemether at a low dose over a 3-month period (92 consecutive days) in dogs. Intramuscular administration of 6 mg kg-1 artemether induced a decreased red blood cell (RBC) count (anemia), concurrent extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. We also observed a prolonged QT interval and neuropathic changes in the central nervous system, which demonstrated the cortex and motor neuron vulnerability, but no behavioral changes. Following treatment with artesunate, we observed a decreased heart rate, which was most likely due to cardiac conduction system damage, as well as a deceased RBC count, extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. However, in contrast to treatment with artemether, neurotoxicity was not observed following treatment with artesunate. In addition, ultra-structural examination by transmission electron microscopy showed mitochondrial damage following treatment with artesunate. These findings demonstrated the spectrum of toxic changes that result upon treatment with artesunate and artemether and show that the prolonged administration of low doses of these derivatives result in diverse toxicity profiles. |
| first_indexed | 2024-04-12T01:21:28Z |
| format | Article |
| id | doaj.art-eda8b69b17784616b7d83d94ca816e50 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T01:21:28Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-eda8b69b17784616b7d83d94ca816e502022-12-22T03:53:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9403410.1371/journal.pone.0094034Subchronic toxicological study of two artemisinin derivatives in dogs.Ji-ye YinHe-mei WangQuan-jun WangYan-sheng DongGang HanYong-biao GuanKe-yong ZhaoWen-sheng QuYe YuanXiao-xin GaoShu-fang JingRi-gao DingThe objective of our study was to profile and compare the systematic changes between orally administered artesunate and intramuscularly injected artemether at a low dose over a 3-month period (92 consecutive days) in dogs. Intramuscular administration of 6 mg kg-1 artemether induced a decreased red blood cell (RBC) count (anemia), concurrent extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. We also observed a prolonged QT interval and neuropathic changes in the central nervous system, which demonstrated the cortex and motor neuron vulnerability, but no behavioral changes. Following treatment with artesunate, we observed a decreased heart rate, which was most likely due to cardiac conduction system damage, as well as a deceased RBC count, extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. However, in contrast to treatment with artemether, neurotoxicity was not observed following treatment with artesunate. In addition, ultra-structural examination by transmission electron microscopy showed mitochondrial damage following treatment with artesunate. These findings demonstrated the spectrum of toxic changes that result upon treatment with artesunate and artemether and show that the prolonged administration of low doses of these derivatives result in diverse toxicity profiles.http://europepmc.org/articles/PMC3989207?pdf=render |
| spellingShingle | Ji-ye Yin He-mei Wang Quan-jun Wang Yan-sheng Dong Gang Han Yong-biao Guan Ke-yong Zhao Wen-sheng Qu Ye Yuan Xiao-xin Gao Shu-fang Jing Ri-gao Ding Subchronic toxicological study of two artemisinin derivatives in dogs. PLoS ONE |
| title | Subchronic toxicological study of two artemisinin derivatives in dogs. |
| title_full | Subchronic toxicological study of two artemisinin derivatives in dogs. |
| title_fullStr | Subchronic toxicological study of two artemisinin derivatives in dogs. |
| title_full_unstemmed | Subchronic toxicological study of two artemisinin derivatives in dogs. |
| title_short | Subchronic toxicological study of two artemisinin derivatives in dogs. |
| title_sort | subchronic toxicological study of two artemisinin derivatives in dogs |
| url | http://europepmc.org/articles/PMC3989207?pdf=render |
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