Husain Kazim, Whitworth Craig, Somani Satu M, Rybak Leonard P
Department of Surgery, Southern Illinois University, School of Medicine, Springfield, IL 62794, USA.
Biomed Environ Sci. 2005 Jun;18(3):198-206.
To investigate the alterations in auditory brainstem evoked responses (ABRs) and the changes of carboplatin-induced ototoxicity in the cochlear oxidant/antioxidant systems and otoprotection by an antioxidant lipoate.
Male wistar rats were divided into four groups and treated as follows: 1) vehicle (saline) control, 2) carboplatin (256 mg/kg, i.p.), 3) lipoate (100 mg/kg, i.p.), 4) lipoate + carboplatin. Post-treatment ABRs were performed after four days and rats were sacrificed with their cochleae harvested and analyzed.
Carboplatin significantly elevated ABR threshold above the pretreatment thresholds. Lipoate+carboplatin treated rats showed decreased elevation of hearing threshold. Carboplatin significantly depleted cochlear reduced to oxizized glutathione (GSH/GSSG) ratio, whereas lipoate+carboplatin treatment increased GSH/GSSG ratio. Carboplatin significantly decreased cochlear copper zinc-superoxide dismutase (CuZn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST) activities and enzyme protein expressions and a significant increase in Mn-SOD activity, protein expression and malondialdehyde (MDA) level. Cochlear antioxidant enzyme activities, enzyme protein expressions and MDA level were partially restored in lipoate+carboplatin treated rats, compared to carboplatin alone.
Carboplatin-induced ototoxicity is related to impairment of cochlear antioxidant system and otoprotection conferred by lipoate is associated with partial sparing of the cochlear antioxidant defense system.
研究听觉脑干诱发电位（ABR）的变化以及卡铂诱导的耳蜗氧化/抗氧化系统的耳毒性改变，以及抗氧化剂硫辛酸的耳保护作用。
将雄性Wistar大鼠分为四组并进行如下处理：1）溶剂（生理盐水）对照组，2）卡铂（256mg/kg，腹腔注射），3）硫辛酸（100mg/kg，腹腔注射），4）硫辛酸+卡铂。处理四天后进行ABR检测，然后处死大鼠，取出耳蜗进行分析。
卡铂使ABR阈值显著高于预处理阈值。硫辛酸+卡铂处理的大鼠听力阈值升高幅度降低。卡铂显著降低了耳蜗中还原型谷胱甘肽与氧化型谷胱甘肽（GSH/GSSG）的比值，而硫辛酸+卡铂处理提高了GSH/GSSG比值。卡铂显著降低了耳蜗铜锌超氧化物歧化酶（CuZn-SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）、谷胱甘肽还原酶（GR）和谷胱甘肽-S-转移酶（GST）的活性及酶蛋白表达，同时显著提高了锰超氧化物歧化酶（Mn-SOD）的活性、蛋白表达及丙二醛（MDA）水平。与单独使用卡铂相比，硫辛酸+卡铂处理的大鼠耳蜗抗氧化酶活性、酶蛋白表达及MDA水平部分恢复。
卡铂诱导的耳毒性与耳蜗抗氧化系统受损有关，硫辛酸的耳保护作用与耳蜗抗氧化防御系统的部分保留有关。
