{Reference Type}: Journal Article
{Title}: Ezetimibe protects against Gentamycin-induced ototoxicity in rats by antioxidants, anti-inflammatory mechanisms, and BDNF upregulation.
{Author}: Abd-Elhafiz HI;Faried MA;Khodir SA;Moaty AS;Sweed EM;
{Journal}: Immunopharmacol Immunotoxicol
{Volume}: 0
{Issue}: 0
{Year}: 2024 Aug 13
{Factor}: 3.712
{DOI}: 10.1080/08923973.2024.2390463
{Abstract}: <B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>EZE can safeguard inner ear tissues from GM via antioxidant, anti-inflammatory, and antiapoptotic mechanisms, as well as upregulation of BDNF mechanisms.