■听力损失的威胁已成为普遍现实。庆大霉素(GM)可导致耳毒性,并可能导致永久性听力损失。这项研究旨在阐明降血脂药物依泽替米贝(EZE)是否具有保护大鼠免受GM诱导的耳毒性的潜在机制。
■将30只白化病雄性Wister大鼠分成3组,每组十个:对照,GM,和GM+EZE。实验结束时,大鼠通过听性脑干反应(ABR)进行听阈评估,颈动脉血流速度(CBV),和电阻(CVR)测量,除了血清丙二醛(MDA)的生化评估,一氧化氮(NO),过氧化氢酶(CAT),血红素氧合酶-1(HO-1),和肿瘤坏死因子-α(TNF-α)。此外,实时PCR用于定量脑源性神经营养因子(BDNF)的水平。还通过组织学和免疫组织化学方法研究了耳蜗。通用汽车透露CVR显着增加,MDA,NO,和TNF-α以及ABR的显着降低,CBV,CAT,HO-1和耳蜗BDNF表达。EZE补充显示,除CBV外,ARB显着升高,CVR下降,并通过抗氧化剂保护耳蜗组织,抗炎,和通过下调Caspase-3免疫反应的抗凋亡机制,上调增殖细胞核抗原(PCNA)免疫反应,以及耳蜗BDNF表达的上调。BDNF与MDA呈显著负相关,NO,TNF-α,COX一2和caspase-3的免疫反应与CAT、HO-1和PCNA免疫反应。
■EZE可以通过抗氧化剂保护内耳组织免受GM的侵害,抗炎,和抗凋亡机制,以及BDNF机制的上调。
UNASSIGNED: The threat of hearing loss has become a universal reality. Gentamycin (GM) can lead to ototoxicity and may result in permanent hearing loss. This study aimed to elucidate whether the hypolipidemic drug Ezetimibe (EZE) has a possible underlying mechanism for protecting rats from GM-induced ototoxicity.
UNASSIGNED: 30 male Wister albino rats were separated into three groups, ten in each group: control, GM, and GM + EZE. At the end of the experiment, rats underwent hearing threshold evaluation via auditory brainstem response (ABR), carotid artery blood flow velocity (CBV), and resistance (CVR) measurement, in addition to a biochemical assessment of serum malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), hemeOxygenase-1 (HO-1), and tumor necrosis factor-α (TNF-α). Also, real-time PCR was employed to quantify the levels of brain-derived neurotrophic factor (
BDNF). Cochlea was also studied via histological and immunohistochemical methods. GM revealed a significant increase in CVR, MDA, NO, and TNF-α and a significant decrease in ABR, CBV, CAT, HO-1, and cochlear
BDNF expression. EZE supplementation revealed a significant rise in ARB in addition to CBV and a decline in CVR and protected cochlear tissues via antioxidant, anti-inflammatory, and antiapoptotic mechanisms via downregulating Caspase-3 immunoreaction, upregulating proliferating cellular nuclear antigen (PCNA) immunoreaction, and upregulating of the cochlear
BDNF expression. Correlations were significantly negative between
BDNF and MDA, NO, TNF-α, COX 2, and caspase-3 immunoreaction and significantly positive with CAT, HO-1, and PCNA immunoreaction.
UNASSIGNED: EZE can safeguard inner ear tissues from GM via antioxidant, anti-inflammatory, and antiapoptotic mechanisms, as well as upregulation of
BDNF mechanisms.