Related Experiment Video
Updated: Jun 22, 2026
Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice
Published on: October 27, 2014
Ocular toxicity caused by Paclitaxel in neonatal sprague-dawley rats
Maki Kuwata1, Katsuhiko Yoshizawa, Miyo Matsumura
1Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
Insights
Paclitaxel (PTX) can cause cataracts and retinal dysplasia in neonatal rats at doses of 4 mg/kg or higher administered at birth. Lower doses or later administration did not result in ocular toxicity, highlighting the importance of careful dosing during early development.
Area of Science:
- Ophthalmology
- Toxicology
- Developmental Biology
Background:
- The ocular toxicity of paclitaxel (PTX) in neonates remains unevaluated.
- Paclitaxel is a widely used chemotherapy agent with known systemic toxicities.
Purpose of the Study:
- To investigate the toxic effects of paclitaxel on neonatal rat eyes.
- To determine the dose-dependent and age-dependent ocular toxicity of paclitaxel.
Main Methods:
- Sprague-Dawley rats were administered varying doses of paclitaxel (PTX) intraperitoneally at different ages (0 days, 14 days, 12-18 weeks).
- Ocular tissues were examined histologically 1 and 7 days post-administration.
- Doses ranged from 0 to 8 mg/kg, with specific focus on neonatal exposure.
Main Results:
- Neonatal rats receiving 4 mg/kg or more of PTX at 0 days of age developed cataracts and retinal dysplasia.
- Histological findings included lens epithelial cell apoptosis and degeneration, indicative of cataracts.
- Retinal findings showed apoptosis in the neuroblastic layer and rosette formation, suggestive of retinal dysplasia.
Conclusions:
- A threshold dose of 4 mg/kg paclitaxel administered at 0 days of age can induce cataracts and retinal dysplasia in neonatal rats.
- Lower doses (2 mg/kg at 0 days) or later administration (14 days or older) did not cause ocular damage.
- Careful consideration of paclitaxel dosage and timing is crucial during early developmental stages to prevent ocular toxicity.
Background:
The toxic effects of paclitaxel (PTX) on neonatal eyes have not been evaluated.
Materials And Methods:
PTX was dissolved in solvent containing polyethoxylated castor oil and intraperitoneally administered to male and female Sprague-Dawley rats at a dose of 0, 2, 4 and 8 mg/kg at 0 day of age, 4 mg/kg at 14 days of age, or 8 mg/kg at 12-18 weeks of age. Eyes were histologically examined 1 and/or 7 days after PTX.
Results:
Male and female rats that received 4 mg/kg or more of PTX at 0 days of age developed cataracts and retinal dysplasias, while the rats that received other dosing regimens did not develop ocular lesions. Epithelial cells in the lens were apoptotic on day 1, and lens fibers were degenerative at day 7, indicating the development of cataracts. Scattered foci of apoptosis in the neuroblastic layer of the retina on day 1, and rosettes were seen on day 7, suggestive of retinal dysplasia.
Conclusion:
Neonatal rats that received a threshold dose of PTX (4 mg/kg) at a critical period (0 days of age) developed cataracts and retinal dysplasia; however, the 2 mg/kg dose at 0 days of age and the 4 or 8 mg/kg dose at 14 days of age or older caused no ocular damage. Thus, the determination of the dose and timing of PTX treatment administered during the early developmental stage requires great care to avoid ocular toxicity.
