Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA.
Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA.
Int J Audiol. 2023 Feb;62(2):151-158. doi: 10.1080/14992027.2021.2022790. Epub 2022 Jan 11.
To elucidate D-methionine's (D-met) dose and time rescue parameters from steady-state or impulse noise-induced permanent threshold shift (PTS) and determine D-met rescue's influence on serum and cochlear antioxidant levels.
Five D-met doses at 0, 50, 100, or 200 mg/kg/dose administered starting at 1, 24, or 36 hours post steady-state or impulse noise exposure. Auditory brainstem responses at baseline and 21 days post-noise measured PTS. Serum (superoxide dismutase [SOD], catalase [CAT],, glutathione reductaseand glutathione peroxidase [GPx]) and cochlear (Glutathione [GSH] and glutathione disulphide [GSSG]) antioxidant levels measured physiological impact.
(10/study group; 6-8/confirmatory groups).
D-met significantly reduced PTS for impulse noise (100 mg [2, 6, 14 and 20 kHz]; 200 mg [2, 14 and 20 kHz]) and steady-state noise (all dosing groups, time parameters and tested frequencies). PTS reduction did not significantly vary by rescue time. D-met significantly increased serum SOD (100 and 200 mg for 24 hour rescue) and GPx (50 mg/kg at 24 hour rescue) at 21 days post-noise. Cochlear GSH and GSSG levels were unaffected relative to control.
D-met rescues from steady-state and impulse noise-induced PTS even when administered up to 36 hours post-noise and dose-dependently influences serum antioxidant levels even 21 days post-noise. D-met's broad and effective dose/time window renders it a promising antioxidant rescue agent.
阐明 D-蛋氨酸(D-met)对稳定态或脉冲噪声致永久性阈移(PTS)的剂量和时间解救参数,并确定 D-met 解救对血清和耳蜗抗氧化水平的影响。
在稳定态或脉冲噪声暴露后 1、24 或 36 小时开始,给予 5 个 D-met 剂量(0、50、100 或 200mg/kg/剂量)。在噪声后 21 天测量听性脑干反应的 PTS。测量血清(超氧化物歧化酶[SOD]、过氧化氢酶[CAT]、谷胱甘肽还原酶和谷胱甘肽过氧化物酶[GPx])和耳蜗(谷胱甘肽[GSH]和谷胱甘肽二硫化物[GSSG])抗氧化水平以测量生理影响。
(每组 10 只;每组 6-8 只为验证组)。
D-met 显著降低了脉冲噪声(100mg [2、6、14 和 20kHz];200mg [2、14 和 20kHz])和稳定态噪声(所有给药组、时间参数和测试频率)的 PTS。解救时间对 PTS 降低没有显著影响。D-met 显著增加了噪声后 21 天的血清 SOD(24 小时解救时 100 和 200mg)和 GPx(24 小时解救时 50mg/kg)。与对照组相比,耳蜗 GSH 和 GSSG 水平没有变化。
D-met 可从稳定态和脉冲噪声引起的 PTS 中解救出来,即使在噪声后 36 小时给予,并且剂量依赖性地影响血清抗氧化水平,甚至在噪声后 21 天。D-met 广泛而有效的剂量/时间窗口使其成为一种有前途的抗氧化解救剂。