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Published on: November 18, 2016
Hypersegmented megakaryocytes and megakaryocytes with multiple separate nuclei in dogs treated with PNU-100592, an
1Worldwide Toxicology, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49001, USA.
Abstract:
Megakaryocytes in normal dogs have a variety of nuclear forms. The most common variations are a single large multilobed nucleus or a segmented nucleus consisting of irregular nuclear lobes joined by strands of chromatin. Exaggerated segmentation (hypersegmentation) of the nucleus occurs in a small number of megakaryocytes. Megakaryocytes with multiple separate nuclei are infrequently observed. In a 1-mo toxicology study in young adult beagle dogs with PNU-100592, a new oxazolidinone antibacterial agent, a large increase in the number of megakaryocytes with hypersegmented nuclei and multiple separate nuclei was observed. The group mean platelet count was slightly decreased for most PNU-100592-treated groups. Siderocytes were observed on peripheral blood smears, and ring sideroblasts were present on bone marrow smears. Minimal to mild toxicologic lesions were observed in the large intestine, rectum, kidneys, liver, and testes, primarily in the high-dose group. PNU-100592 may be useful in the study of the regulation of endomitosis during megakaryocytopoiesis in the dog.
Insights
A toxicology study in beagle dogs revealed that the antibacterial agent PNU-100592 significantly increased abnormal megakaryocyte nuclear forms. This finding may offer insights into megakaryocytopoiesis regulation.
Area of Science:
- Veterinary Pathology
- Hematology
- Toxicology
Background:
- Megakaryocytes exhibit diverse nuclear morphologies in normal dogs, including multilobed and segmented nuclei.
- Hypersegmentation and multiple separate nuclei are infrequent in canine megakaryocytes.
Purpose of the Study:
- To evaluate the effects of PNU-100592, an oxazolidinone antibacterial, on megakaryocytopoiesis in young adult beagle dogs.
- To investigate potential alterations in megakaryocyte nuclear morphology and platelet counts.
Main Methods:
- A 1-month toxicology study was conducted using young adult beagle dogs.
- Peripheral blood smears and bone marrow smears were analyzed.
- Hematologic parameters, including platelet counts, were monitored.
Main Results:
- PNU-100592 administration led to a notable increase in megakaryocytes with hypersegmented and multiple separate nuclei.
- A slight decrease in mean platelet count was observed in most treated groups.
- Siderocytes and ring sideroblasts were identified, indicating potential iron metabolism disturbances.
Conclusions:
- PNU-100592 induces significant changes in canine megakaryocyte nuclear morphology.
- The drug may impact megakaryocytopoiesis and platelet production.
- PNU-100592 could serve as a tool for studying endomitosis regulation in canine megakaryocytopoiesis.
