Said Toihiri, Dutot Mélody, Christon Raymond, Beaudeux Jean-Louis, Martin Chantal, Warnet Jean-Michel, Rat Patrice
Laboratoire de Toxicologie, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes Paris, Paris, France.
Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5000-6. doi: 10.1167/iovs.07-0229.
Ocular side effects in patients using eye drops may be due to intolerance to the vector used in eye drops. Castor oil is the commonly used lipophilic vector but has been shown to be cytotoxic. Effects on cells of four oils (olive, camelina, Aleurites moluccana, maize) were compared with those of castor oil in human conjunctival cells.
Human conjunctival cells were incubated with the oils for 15 minutes. After a 24-hour recovery period, cells were tested for viability, proliferation, apoptosis (P2X7 cell death receptor and caspase 3 activation), intracellular redox potential, and reactive oxygen species production. Fatty acid incorporation in cell membranes was also analyzed. In vivo ocular irritation was assessed using the Draize test.
Compared to the four other oils, castor oil was shown to induce significant necrosis and P2X7 cell death receptor and caspase 3 activation and to enhance intracellular reactive oxygen species production. Aleurites moluccana and camelina oils were not cytotoxic and increased cell membrane omega-3 fatty acid content. None of the five tested oils showed any in vivo ocular irritation.
The results demonstrated that castor oil exerts cytotoxic effects on conjunctival cells. This cytotoxicity could explain the side effects observed in some patients using eye drops containing castor oil as a vehicle. The lack of cytotoxic effects observed with the four other oils, Aleurites, camelina, maize, and olive, suggest that they could be chosen to replace castor oil in ophthalmic formulations.
使用眼药水的患者出现眼部副作用可能是由于对眼药水中所用载体不耐受。蓖麻油是常用的亲脂性载体,但已被证明具有细胞毒性。将四种油(橄榄油、亚麻荠油、石栗油、玉米油)对人结膜细胞的影响与蓖麻油进行比较。
将人结膜细胞与这些油孵育15分钟。经过24小时的恢复期后,检测细胞的活力、增殖、凋亡(P2X7细胞死亡受体和半胱天冬酶3激活)、细胞内氧化还原电位和活性氧生成。还分析了细胞膜中脂肪酸的掺入情况。使用Draize试验评估体内眼部刺激性。
与其他四种油相比,蓖麻油显示出可诱导显著的坏死、P2X7细胞死亡受体和半胱天冬酶3激活,并增强细胞内活性氧生成。石栗油和亚麻荠油没有细胞毒性,且增加了细胞膜ω-3脂肪酸含量。所测试的五种油均未显示出任何体内眼部刺激性。
结果表明蓖麻油对结膜细胞具有细胞毒性作用。这种细胞毒性可以解释一些使用含有蓖麻油作为载体的眼药水的患者所观察到的副作用。其他四种油,即石栗油、亚麻荠油、玉米油和橄榄油,未观察到细胞毒性作用,这表明它们可被选择用于替代眼科制剂中的蓖麻油。