Repeat dose and reproductive toxicity of thrombopoietin mimic peptide in Sprague-Dawley rats
Copyright © 2024. Published by Elsevier Inc..
Thrombopoietin mimic peptide (TMP) is a novel thrombopoietin receptor agonist. In this report, we evaluated the potential toxicity of TMP in repeat-dose toxicity and reproductive/developmental toxicity studies (segment Ⅰ, Ⅱ, Ⅲ). TMP was administered subcutaneously to Sprague-Dawley (SD) rats at 5, 15 or 50 mcg/kg. In repeat-dose toxicity study, the rats were administrated three times a week for 26 week with a 4-week recovery. TMP could produce anti-drug antibodies and induce platelet counts increase, megakaryocyte proliferation. While platelet counts decreased gradually and returned to normal after 4 weeks in male rats. Other significant findings included myelofibrosis of bone marrow, hepatic extramedullary hematopoiesis, splenic lymphocytic depletion and bone hyperostosis. All treatment-related effects were reversed following recovery. The NOAEL of repeat-dose toxicity in female rats is 5 mcg/kg. In the reproductive/developmental toxicity (segment Ⅰ, Ⅲ), no deaths occurred, and no general toxicological effects or abnormal reproductive functions were observed. In embryo-fetal developmental toxicity study (segment Ⅱ), the number of resorbed fetuses in the 50 mcg/kg group was significantly increased. The NOAEL as related to reproductive/developmental toxicity in these rats was 15 mcg/kg.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:148 |
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| Enthalten in: |
Regulatory toxicology and pharmacology : RTP - 148(2024) vom: 21. März, Seite 105581 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Qiu, Shidong [VerfasserIn] |
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| Links: |
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| Themen: |
9014-42-0 |
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| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.yrtph.2024.105581 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368316971 |
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| 520 | |a Thrombopoietin mimic peptide (TMP) is a novel thrombopoietin receptor agonist. In this report, we evaluated the potential toxicity of TMP in repeat-dose toxicity and reproductive/developmental toxicity studies (segment Ⅰ, Ⅱ, Ⅲ). TMP was administered subcutaneously to Sprague-Dawley (SD) rats at 5, 15 or 50 mcg/kg. In repeat-dose toxicity study, the rats were administrated three times a week for 26 week with a 4-week recovery. TMP could produce anti-drug antibodies and induce platelet counts increase, megakaryocyte proliferation. While platelet counts decreased gradually and returned to normal after 4 weeks in male rats. Other significant findings included myelofibrosis of bone marrow, hepatic extramedullary hematopoiesis, splenic lymphocytic depletion and bone hyperostosis. All treatment-related effects were reversed following recovery. The NOAEL of repeat-dose toxicity in female rats is 5 mcg/kg. In the reproductive/developmental toxicity (segment Ⅰ, Ⅲ), no deaths occurred, and no general toxicological effects or abnormal reproductive functions were observed. In embryo-fetal developmental toxicity study (segment Ⅱ), the number of resorbed fetuses in the 50 mcg/kg group was significantly increased. The NOAEL as related to reproductive/developmental toxicity in these rats was 15 mcg/kg | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Wang, Xiaobo |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiue |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Guoyue |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Teng, Suling |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Peilu |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Zenglin |e verfasserin |4 aut | |
| 700 | 1 | |a Mu, Yanling |e verfasserin |4 aut | |
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