| Backgroud and objects:Gentamicin ototoxicity is irreversible and limits its clinical use. The present study was designed to investigate the possible protective effects of a new drug—r LZ-8 on gentamicin ototoxicity in albino guinea pigs from aspects of auditory function and morphology, in order to find a potential drug against gentamicin ototoxicy.Materials and methods:Select normal, healthy and white guinea pigs 36(72 ears). Animals were divided into six experimental groups, 6 in each group:Ⅰ, a sham control group : from day1 to day15 given an intra-peritoneal(i.P.) injection of 2 ml saline twice at 8:00 and 16:00; from day2 to day15 given an intramuscular(i.m.) injection 2.5mg/Kg at 8:30; Ⅱ, gentamicin group(GM), from day1 to day15 given an in i.P. injection of 2 ml saline twice at 8:00 and 16:00; from day2 to day15 treated with an i.m. of GM(100 mg/Kg) at 8:30; Ⅲ, gentamicin + EGb group(GM+EGb), from day1 to day15 given an i.P. injection of EGb(7mg/Kg) twice at 8:00 and 16:00; from day2 to day15 treated with an i.m. of GM(same dose as group Ⅱ) at 8:30; Ⅳ, r LZ-8 low dosage group(GM+r LZ-8, 28ug/Kg), from day1 to day15 given an i.P. injection of r LZ-8(28ug/Kg) twice at 8:00 and 16:00; from day2 to day15 treated with an i.m. of GM(same dose as group Ⅱ) at 8:30; Ⅴ, r LZ-8 middle dosage group(GM+r LZ-8, 56ug/Kg), from day1 to day15 given an i.P. injection of r LZ-8(56ug/Kg) twice at 8:00 and 16:00; from day2 to day15 treated with an i.m. of GM(same dose as group Ⅱ) at 8:30. Ⅵ,r LZ-8 high dosage group(GM+r LZ-8, 112ug/Kg), from day1 to day15 given an i.P. injection of r LZ-8(112ug/Kg) twice at 8:00 and 16:00; from day2 to day15 treated with an i.m. of GM(same dose as group Ⅱ) at 8:30. Auditory function was evaluated by recording auditory brainstem responses(ABR) and distortion product otoacoustic emission(DPOAE) the day before and the day after the treatment. Record changes of the threshold of ABR,the latency of Ⅲwave, and the amplitude of DPOAE at frequencies of 1,2,4,6k Hz. The morphological changes were analyzed by surface preparation technique and scanning electron microscope(SEM). Record the quantity of hair cells and the damage of the surface of corti.Results:1. Weight of GM group decreased significantly after treated with GM(P<0.01), while r LZ-8 low dosage group decreased less than GM group, and had no significant difference with GM+EGb group(P>0.01); 2. ABR threshold of GM group had increased by 38.50±3.94 d B n HL, and the latency of wave Ⅲ was longer after treated with GM(P<0.01), While r LZ-8 low dosage group had no significant difference after treatment with GM compared with the sham control(P>0.01); ABR threshold of GM+EGb group increased significantly after treated with GM(P<0.01); 3. The amplitude of GM group decreased significantly, and had significantly difference with r LZ-8 low dosage group at 1, 2, 4, 6k Hz frequencies,with L1/L2=65/55 d B SPL(P<0.01); 4. Surface preparation technique and scanning electron microscope(SEM) indicate that the basal turn of GM group had been significantly damaged with loss of outer hair cells, scattered arrangement, fusion, lodging and defect of cilia. The damage was much more lighter from the basal to the apex. The survival rate of GM group was only about 30%. While the survival rate and the morphology of the outer hairs of r LZ-8 low dosage group had no significantly difference with the sham control group.Conclusion:1. GM can raise the threshold of ABR, especially at the high frequencies; GM can damage the morphology of outer hair, especially in the basal turn.2. r LZ-8 of low dosage can keep away guinea pigs from systemic toxicity of GM and protect hair cells from damage, keeping their function and integrity.3. The effects of r LZ-8 depend on its dosage. |
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