Ocular toxicity caused by Paclitaxel in neonatal sprague-dawley rats.
BACKGROUND
The toxic effects of paclitaxel (PTX) on neonatal eyes have not been evaluated.


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.


CONCLUSIONS
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.
Kuwata
Maki
M
Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
Yoshizawa
Katsuhiko
K
Matsumura
Miyo
M
Takahashi
Kanji
K
Tsubura
Airo
A
D000818:Animals; D000831:Animals, Newborn; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D002386:Cataract / Q000139:chemically induced* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D007908:Lens, Crystalline / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D008297:Male; D017239:Paclitaxel / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D015792:Retinal Dysplasia / Q000139:chemically induced* / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel