Fetoni A R, Sergi B, Ferraresi A, Paludetti G, Troiani D
Institute of Otolaryngology, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Acta Otolaryngol. 2004 May;124(4):421-6. doi: 10.1080/00016480410016559.
To investigate the possible protective effects of alpha-tocopherol and tiopronin against cisplatin-induced cochlear damage. Cisplatin ototoxicity and nephrotoxicity seem to result from the inhibition of cochlear antioxidant defences, causing an increase in the amount of reactive oxygen species. Antioxidants, such as alpha-tocopherol and tiopronin, are able to suppress lipid peroxidation, thus attenuating tissue damage.
Hartley albino guinea pigs were used. The animals were treated for 7 consecutive days with either (I) cisplatin alone, (II) cisplatin+alpha-tocopherol acetate, (III) cisplatin+tiopronin, (IV) cisplatin+alpha-tocopherol acetate+tiopronin, (V) alpha-tocopherol acetate alone or (VI) tiopronin alone. Changes in cochlear function were characterized by means of compound action potential threshold shifts. After the functional testing, tympanic bullae were removed and processed for morphological examination of the sensorineural epithelium. Renal function was evaluated by measuring serum blood urea nitrogen and creatinine levels.
Cisplatin induced progressive high-frequency hearing loss of 40-50 dB SPL. Alpha-tocopherol and tiopronin co-therapy significantly slowed the progression of hearing loss. Treatment with alpha-tocopherol acetate or tiopronin alone was less effective. Morphological observations showed an important loss of outer hair cells and degeneration of the organ of Corti in the basal and middle turns. Injection of both alpha-tocopherol and tiopronin reduced cochlear outer hair cell loss more than treatment with a single drug. Beneficial effects of alpha-tocopherol and tiopronin on cisplatin-induced nephrotoxicity were observed.
This study supports the hypothesis that alpha-tocopherol and tiopronin interfere with cisplatin-induced damage, and suggests that concurrent treatment with the two drugs can be useful in protecting against hearing loss.
研究α-生育酚和硫普罗宁对顺铂所致耳蜗损伤的可能保护作用。顺铂的耳毒性和肾毒性似乎是由于耳蜗抗氧化防御机制受到抑制，导致活性氧含量增加所致。抗氧化剂，如α-生育酚和硫普罗宁，能够抑制脂质过氧化，从而减轻组织损伤。
使用哈特利白化豚鼠。将动物连续7天分别用以下方法处理：（I）单独使用顺铂，（II）顺铂+醋酸α-生育酚，（III）顺铂+硫普罗宁，（IV）顺铂+醋酸α-生育酚+硫普罗宁，（V）单独使用醋酸α-生育酚，或（VI）单独使用硫普罗宁。通过复合动作电位阈值变化来表征耳蜗功能的变化。功能测试后，取出鼓泡并进行处理，以对感觉神经上皮进行形态学检查。通过测量血清血尿素氮和肌酐水平来评估肾功能。
顺铂导致40 - 50 dB SPL的进行性高频听力损失。α-生育酚和硫普罗宁联合治疗显著减缓了听力损失的进展。单独使用醋酸α-生育酚或硫普罗宁治疗效果较差。形态学观察显示，基底转和中转的外毛细胞大量丢失，柯蒂氏器退化。同时注射α-生育酚和硫普罗宁比单一药物治疗减少了更多的耳蜗外毛细胞丢失。观察到α-生育酚和硫普罗宁对顺铂所致肾毒性有有益作用。
本研究支持α-生育酚和硫普罗宁可干扰顺铂所致损伤的假说，并表明两种药物联合治疗对预防听力损失可能有用。
