Abstract Title:

Ginkgolide B protects against cisplatin-induced ototoxicity: enhancement of Akt-Nrf2-HO-1 signaling and reduction of NADPH oxidase.

Abstract Source:

Cancer Chemother Pharmacol. 2015 May ;75(5):949-59. Epub 2015 Mar 7. PMID: 25749575

Abstract Author(s):

Weijun Ma, Juan Hu, Ying Cheng, Junli Wang, Xiaotong Zhang, Min Xu

Article Affiliation:

Weijun Ma


Cisplatin is a widely used chemotherapeutic drug for the treatment of various cancers. However, the ototoxicity severely limited its maximum dose. The present study was designed to evaluate the effect of Ginkgolide B (GB), a major component of Ginkgo biloba extracts, on cisplatin-induced ototoxicity and to elucidate the molecular mechanism in vitro and in vivo. In HEI-OC1 auditory cells, GB concentration-dependently inhibited the reduction of cell viability and increase in apoptosis exerted by cisplatin. Cisplatin-activated mitochondrial apoptotic molecular events were significantly inhibited by GB. In addition, GB notably suppressed the increase in NOX2 and p47(phox) expression and the decrease in nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in cisplatin-exposed cells. Inhibition of Nrf2 using SiRNA and blockage of HO-1 by zinc protoporphyrin IX (ZnPP) suppressed the protective effects of GB. Moreover, GB prevented cisplatin-induced reduction of Akt phosphorylation and LY294002, an inhibitor of PI3 K/Akt signaling, blocked the anti-apoptotic effect of GB in cisplatin-treated cells. Furthermore, the protective effect of GB was tested in cisplatin-exposed rats. GB treatment markedly protected animals against cisplatin-induced hearing loss and vestibular dysfunction. Inhibition of Akt and HO-1significantly suppressed the improvement in hearing loss and vestibular dysfunction in GB-treated rats. We demonstrate that GB decreases ROS generation through reducing NOX2 expression and enhancing activity through Akt-Nrf2-HO-1 pathway, resulting in inhibition of mitochondrial apoptosis and finalreduction of cisplatin-induced ototoxicity in vitro and in vivo. Our findings have gained an insight into the mechanism of GB-exerted protective effect against cisplatin-induced ototoxicity.

Study Type : Animal Study, In Vitro Study

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