Repeat dose and reproductive toxicity of thrombopoietin mimic peptide in Sprague-Dawley rats. 2024

Shidong Qiu, and Yuji Liang, and Xiaobo Wang, and Xiue Li, and Guoyue Wei, and Peng Xiao, and Suling Teng, and Peilu Sun, and Lei Song, and Zenglin Zhao, and Yanling Mu
School of Pharmaceutical Sciences, Shandong First Medical University (Institute of Materia Medica), Jinan, 250117, China.

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.

UI MeSH Term Description Entries
D008297 Male Males
D012098 Reproduction The total process by which organisms produce offspring. (Stedman, 25th ed) Human Reproductive Index,Human Reproductive Indexes,Reproductive Period,Human Reproductive Indices,Index, Human Reproductive,Indexes, Human Reproductive,Indices, Human Reproductive,Period, Reproductive,Periods, Reproductive,Reproductive Index, Human,Reproductive Indices, Human,Reproductive Periods
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013926 Thrombopoietin A humoral factor that stimulates the production of thrombocytes (BLOOD PLATELETS). Thrombopoietin stimulates the proliferation of bone marrow MEGAKARYOCYTES and their release of blood platelets. The process is called THROMBOPOIESIS. Megakaryocyte Growth and Development Factor,c-mpl Ligand,MGDF Factor,Megakaryocyte Colony Stimulating Factor,Myeloproliferative Leukemia Virus Oncogene Ligand,Thrombocytopoiesis-Stimulating Factor,Thrombocytopoietin,mpl Ligand,Ligand, c-mpl,Ligand, mpl,Thrombocytopoiesis Stimulating Factor
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D019055 No-Observed-Adverse-Effect Level The highest dosage administered that does not produce toxic effects. NOAEL,No-Observed-Effect Level,Acceptable Daily Intake,Tolerable Daily Intake,Acceptable Daily Intakes,Daily Intake, Acceptable,Daily Intake, Tolerable,Daily Intakes, Acceptable,Daily Intakes, Tolerable,Intake, Acceptable Daily,Intake, Tolerable Daily,Intakes, Acceptable Daily,Intakes, Tolerable Daily,Level, No-Observed-Adverse-Effect,Level, No-Observed-Effect,Levels, No-Observed-Adverse-Effect,Levels, No-Observed-Effect,No Observed Adverse Effect Level,No Observed Effect Level,No-Observed-Adverse-Effect Levels,No-Observed-Effect Levels,Tolerable Daily Intakes

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