Three-month effects of MDL 19,660 on the canine platelet and erythrocyte

Yarrington, J. T.

doi:10.1016/0272-0590(92)90053-k

Cited by 2 publications

(1 citation statement)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TEM imaging and the CD68 immunohistochemistry stain revealed that marophages played an important role in the retention of SNPs in the spleen. In our study, histological hyperplasia of megakaryocytes in the red pulp of the spleen was observed in SNP treated mice, indicating splenic extramedullary hematopoiesis, which is associated with pathological conditions [30], [31], [32], [33]. Kwon et al demonstrated that inhaled fluorescent magnetic nanoparticles induced extramedullary hematopoiesis in the spleen of mice without pulmonary abnormalities [34].…”

Section: Discussionsupporting

confidence: 60%

Acute Toxicity of Amorphous Silica Nanoparticles in Intravenously Exposed ICR Mice

Wang

et al. 2013

PLoS ONE

110

View full text Add to dashboard Cite

This study aimed to evaluate the acute toxicity of intravenously administrated amorphous silica nanoparticles (SNPs) in mice. The lethal dose, 50 (LD50), of intravenously administrated SNPs was calculated in mice using Dixon's up-and-down method (262.45±33.78 mg/kg). The acute toxicity was evaluated at 14 d after intravenous injection of SNPs at 29.5, 103.5 and 177.5 mg/kg in mice. A silicon content analysis using ICP-OES found that SNPs mainly distributed in the resident macrophages of the liver (10.24%ID/g), spleen (34.78%ID/g) and lung (1.96%ID/g). TEM imaging showed only a small amount in the hepatocytes of the liver and in the capillary endothelial cells of the lung and kidney. The levels of serum LDH, AST and ALT were all elevated in the SNP treated groups. A histological examination showed lymphocytic infiltration, granuloma formation, and hydropic degeneration in liver hepatocytes; megakaryocyte hyperplasia in the spleen; and pneumonemia and pulmonary interstitial thickening in the lung of the SNP treated groups. A CD68 immunohistochemistry stain indicated SNPs induced macrophage proliferation in the liver and spleen. The results suggest injuries induced by the SNPs in the liver, spleen and lungs. Mononuclear phagocytic cells played an important role in the injury process.

show abstract

Section: Discussionsupporting

confidence: 60%

Acute Toxicity of Amorphous Silica Nanoparticles in Intravenously Exposed ICR Mice

Wang

et al. 2013

PLoS ONE

110

View full text Add to dashboard Cite

show abstract

Preclinical toxicity of a new oral anticancer drug, CI-994 (Acetyldinaline), in rats and dogs

et al. 1997

View full text Add to dashboard Cite

CI-994 (acetyldinaline) is an orally active anticancer drug currently in Phase 1 clinical trials. To assess its preclinical toxicity, CI-994 was administered orally as suspensions to Wistar rats (10/sex/dose) and in capsules to beagle dogs (3/sex/dose) once daily for two weeks. Doses were 1.5, 5, and 15 mg/kg for rats (9, 30, and 90 mg/m2, respectively), and 0.5, 2, and 5 mg/kg for dogs (10, 40, and 100 mg/m2, respectively). Systemic exposure was dose-proportional based on toxicokinetic analysis in dogs. Severe clinical signs and mortality occurred at the highest dose in both species beginning on Day 10. Neutropenia, lymphocytopenia, thrombocytopenia, lymphoid depletion, bone marrow hypocellularity, and testicular degeneration were observed in both species, primarily at the mid- and high-doses. Despite continued treatment, neutrophil counts in dogs returned to control levels in Week 2. Other microscopic findings in rats included splenic hematopoietic depletion at all doses and epithelial cell necrosis in various tissues at 15 mg/kg. Additional bone marrow changes in dogs involved myeloid and megakaryocyte hyperplasia at 2 mg/kg and abnormal myeloid and megakaryocyte maturation at 2 and 5 mg/kg. Except for the testicular effects in both species, all changes were reversible within a 4-week (rat) or 9-week (dog) recovery period. The results of these studies show that target organ effects of CI-994 principally involve tissues with rapidly dividing cell populations and that bone marrow suppression is the dose-limiting toxicity. CI-994 also seems to interfere with the release and/or maturation of cells in the bone marrow.

show abstract

Three-month effects of MDL 19,660 on the canine platelet and erythrocyte

Cited by 2 publications

References 20 publications

Acute Toxicity of Amorphous Silica Nanoparticles in Intravenously Exposed ICR Mice

Acute Toxicity of Amorphous Silica Nanoparticles in Intravenously Exposed ICR Mice

Preclinical toxicity of a new oral anticancer drug, CI-994 (Acetyldinaline), in rats and dogs

Contact Info

Product

Resources

About