Glycyrrhizic acid alleviates cisplatin-induced ototoxicity by inhibiting in-flammation of cochlear in C57BL/6J mice
10.3969/j.issn.1000-4718.2024.02.012
- VernacularTitle:甘草酸抑制C57BL/6J小鼠耳蜗炎症减轻顺铂诱导的耳毒性
- Author:
Yuqian ZHANG
1
;
Wenjun JIANG
;
Hao LÜ
;
Zixuan SHENG
;
Ziyun HUANG
;
Wenmin CHAI
;
Jing XIAO
;
Yang LI
;
Li LI
;
Xiansi ZENG
Author Information
1. 嘉兴大学神经科学研究中心,医学院基础医学部,浙江 嘉兴 314000
- Keywords:
cisplatin;
ototoxicity;
glycyrrhizic acid;
cochlear inflammation;
blood-labyrinth barrier
- From:
Chinese Journal of Pathophysiology
2024;40(2):291-300
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To study whether glycyrrhizic acid(GL)can resist the ototoxicity of cisplatin(CDDP)in mice and its molecular mechanism.METHODS:Male C57BL/6J mice were divided into 5 groups:control group,DMSO(5%)group,CDDP(4 mg/kg)group,CDDP+low-dose(50 mg/kg)GL group,and CDDP+high-dose(100 mg/kg)GL group(n=14).Auditory brainstem response(ABR)was used to detect hearing changes of mice.HE staining was used to observe the morphological change of cochlear stria vascular in mice.Evans blue(EB)staining was used to observe the per-meability change of the blood-labyrinth barrier(BLB).Immunohistochemical technique was used to detect the expression and distribution of adhesion protein VE-cadherin and tight junction protein ZO-1 on the cochlear stria.ELISA assay and immunofluorescence technology were employed to detect the expression of tumor necrosis factor-α(TNF-α)and interleu-kin-1β(1L-1β).RESULTS:In CDDP group,ABR waveforms of all frequencies were disturbed,the hearing threshold was significantly increased,and I wave latency was prolonged(P＜0.05).In CDDP+GL group,ABR waveforms of various frequencies were well differentiated,the hearing threshold was significantly decreased,and the latency of I-wave was shortened(P＜0.01).The disordered morphology and more vacuoles in the stria vascularis were observed by HE staining in CDDP group.The GL alleviated CDDP-induced damage in the stria vascularis.In EB staining,CDDP caused an increase in per-meability of BLB(P＜0.01),which was improved by GL treatment(P＜0.01).Immunohistochemical results showed that the expression of VE-cadherin and ZO-1 in CDDP group were decreased(P＜0.01),which was restored in CDDP+GL group(P＜0.01).The ELISA and immunofluorescence results showed that the expression of IL-1β and TNF-α was in-creased after CDDP treatment(P＜0.01),which was restored in CDDP+GL group(P＜0.01).CONCLUSION:The GL alleviates CDDP-induced hearing loss in mice by inhibiting CDDP-induced inflammation and reducing the permeability of BLB.
