Kuwata Maki, Yoshizawa Katsuhiko, Matsumura Miyo, Takahashi Kanji, Tsubura Airo
Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
In Vivo. 2009 Jul-Aug;23(4):555-60.
The toxic effects of paclitaxel (PTX) on neonatal eyes have not been evaluated.
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.
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.
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.
紫杉醇（PTX）对新生动物眼睛的毒性作用尚未得到评估。
将PTX溶解于含聚乙氧基化蓖麻油的溶剂中，于出生第0天、第14天或12 - 18周龄时，以0、2、4和8 mg/kg的剂量对雄性和雌性Sprague-Dawley大鼠进行腹腔注射，其中出生第0天的剂量为4 mg/kg，出生第14天的剂量为4 mg/kg，12 - 18周龄的剂量为8 mg/kg。在PTX注射后1天和/或7天对眼睛进行组织学检查。
出生第0天接受4 mg/kg及以上PTX的雄性和雌性大鼠出现白内障和视网膜发育异常，而接受其他给药方案的大鼠未出现眼部病变。第1天时晶状体上皮细胞发生凋亡，第7天时晶状体纤维发生退变，提示白内障形成。第1天时视网膜神经母细胞层出现散在凋亡灶，第7天时可见玫瑰花结，提示视网膜发育异常。
在关键时期（出生第0天）接受阈值剂量PTX（4 mg/kg）的新生大鼠出现白内障和视网膜发育异常；然而，出生第0天给予2 mg/kg剂量以及出生第14天及以后给予4或8 mg/kg剂量均未造成眼部损伤。因此，在发育早期阶段确定PTX治疗的剂量和时间需要格外谨慎，以避免眼部毒性。
