Sharifzadeh M, Abdollahi M, Behrooz H, Minaii B, Kebriaeezadeh A, Kashani M R, Dehpour A R, Aghaebrahimi N
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran.
Pharmacol Toxicol. 1998 Nov;83(5):220-4. doi: 10.1111/j.1600-0773.1998.tb01472.x.
The effects of chronic lithium co-therapy on the expression of gentamicin and amikacin ototoxicity were tested in guinea-pigs. Intramuscular injection of different doses of gentamicin (5, 10 mg/kg/day) and amikacin (150, 300 mg/kg/day) for three weeks, induced hearing loss consistent with the established pattern of aminoglycoside ototoxicity. Lithium salts remains one of the most widely used treatment for depressive illness. Administration of lithium chloride (600 mg/l, 35 days) in drinking water changed auditory brainstem response in a time-dependent manner. Pretreatment of animals with lithium chloride after seven days induced significant alterations in wave latency and interval. The present study assesses the protective effects of chronic lithium on gentamicin-induced ototoxicity in guinea pig. The results suggest that duration of lithium administration may be involved in auditory brainstem response changes and the observations could be accounted for, at least partially, by lithium- and aminoglycosides-induced perturbations of the phosphoinositide cascade within the inner ear.
在豚鼠身上测试了慢性锂联合治疗对庆大霉素和阿米卡星耳毒性表达的影响。连续三周肌肉注射不同剂量的庆大霉素(5、10毫克/千克/天)和阿米卡星(150、300毫克/千克/天),导致听力损失,这与已确立的氨基糖苷类耳毒性模式一致。锂盐仍然是治疗抑郁症最广泛使用的药物之一。在饮用水中给予氯化锂(600毫克/升,35天)以时间依赖性方式改变听觉脑干反应。在七天后用氯化锂对动物进行预处理会导致波潜伏期和间隔发生显著变化。本研究评估了慢性锂对豚鼠庆大霉素诱导的耳毒性的保护作用。结果表明,锂给药的持续时间可能与听觉脑干反应变化有关,并且这些观察结果至少部分可以由锂和氨基糖苷类药物对内耳磷酸肌醇级联反应的干扰来解释。