Otolaryngology-Head and Neck Surgery, University of Connecticut, Farmington, Connecticut 06030-6228, USA.
Otolaryngol Head Neck Surg. 2011 Jun;144(6):959-61. doi: 10.1177/0194599811399850. Epub 2011 Feb 18.
This study evaluates the ototoxicity of a potential novel ototopical antimicrobial, photoactivated methyl-δ-aminolevulinic acid (M-ALA). Ten CBA/J mice received intratympanic injections of 10 mM M-ALA and 640 nm light source illumination for 7 days, with contralateral ears receiving saline. Auditory-evoked brainstem response (ABR) thresholds (8, 16, 24, and 32 kHz) were determined preinjection and at 1, 30, and 90 days postinjection. Mean ABR thresholds were similar after intratympanic administration of M-ALA and saline (F ratio, 0.001; P = .971). ABR thresholds temporarily increased in both groups (F ratio, 28.52; P = .00) at day 1 postinjection of intratympanic treatments but returned to baseline at day 30 and 90. This temporary elevation was associated with tympanic membrane perforations and granulation tissue at the injection sites, which resolved by day 30 posttreatment. The preliminary findings indicate that intratympanic application of M-ALA with light activation over a 7-day course in a murine model does not produce measurable ototoxicity and is well tolerated.
本研究评估了一种潜在的新型局部抗感染抗菌药物——光激活甲基-δ-氨基酮戊酸（M-ALA）的耳毒性。10 只 CBA/J 小鼠接受了为期 7 天的鼓室内 10 mM M-ALA 和 640nm 光源照射，对侧耳朵接受生理盐水注射。在注射前和注射后 1、30 和 90 天测定听觉脑干反应（ABR）阈值（8、16、24 和 32 kHz）。鼓室内给予 M-ALA 和生理盐水后平均 ABR 阈值相似（F 比，0.001；P =.971）。两组在鼓室内治疗后第 1 天的 ABR 阈值均暂时升高（F 比，28.52；P =.00），但在第 30 和 90 天恢复至基线。这种暂时升高与鼓室膜穿孔和注射部位的肉芽组织有关，这些病变在治疗后第 30 天得到解决。初步研究结果表明，在小鼠模型中，光激活 M-ALA 经鼓室给药，7 天为一疗程，不会产生可测量的耳毒性，且耐受性良好。
