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.
