Protective mechanism of Korean Red Ginseng in cisplatin-induced ototoxicity through attenuation of nuclear factor-κB and caspase-1 activation

Abstract

Cisplatin is an effective anti-cancer drug; however, one of its side effects is irreversible sensorineural hearing damage. Korean Red Ginseng (KRG) has been used clinically for the treatment of various diseases; however, the underlying mechanism of KRG treatment of ototoxicity has not been studied extensively. The present study aimed to further investigate the mechanism of KRG on cisplatin-induced toxicity in auditory HEI-OC1 cells in vitro, as well as in vivo. The pharmacological effects of KRG on cisplatin-induced changes in the hearing threshold of mice were determined, as well as the effect on the impairment of hair cell arrays. In addition, in order to elucidate the protective mechanisms of KRG, the regulatory effects of KRG on cisplatin-induced apoptosis-associated gene levels and nuclear factor-κB (NF-κB) activation were investigated in auditory cells. The results revealed that KRG prevented cisplatin-induced alterations in the hearing threshold of mice as well as the destruction of hair cell arrays in rat organ of Corti primary explants. In addition, KRG inhibited cisplatin-mediated cell toxicity, reactive oxygen species generation, interleukin-6 production, cytochrome c release and activation of caspases-3 in the HEI-OC1 auditory cell line. Furthermore, the results demonstrated that KRG inhibited the activation of NF-κB and caspase-1. In conclusion, these results provided a model for the pharmacological mechanism of KRG and provided evidence for potential therapies against ototoxicity.

Ovarian cysts disappear after 14-day oral regimen of Korean red ginseng extract in letrozole-induced polycystic ovarian syndrome

“…This model did not cause any endometrial hyperplasia; however, any change in uterine weights and the histopathology of the uterus, significant ovarian weight gain, ovarian hyperplasia, and the formation of numerous cysts were the main symptoms of PCOS in this study, which was in accordance to previous animal evidence [1,14] as shown in Fig. 2A.…”

“…In this context, many limitations exist with regard to the prevention, protection, or definite treatment of PCOS, thus increasing the public's concerns toward alternative medications. Korean red ginseng is one of the most popular herbal remedies in other disease models and is known to have certain anti-inflammatory [13] and antioxidant effects [14] through activation of the NF-κB pathway [15]. However, the estrogenic effects of Korean red ginseng extract (KRGE) is still conflicting based on in vitro, in vivo [16] and clinical evaluations of sexual disorders [17].…”

Ginseng: A Qualitative Review of Benefits for Palliative Clinicians

“…186 In several animal models, ginseng protected animals from cisplatin nephrotoxicity and ototoxicity. [187][188][189][190][191][192] Ginseng in rats reduced cisplatininduced nausea and weight loss. 193,194 632…”

Protective Effect of Korean Red Ginseng on Cisplatin Ototoxicity: Is It Effective Enough?

“…KRG extracts, or its specific saponins, were shown to have antiapoptotic and antioxidant properties in various tissues both in vitro and in vivo [8] . Recently, it was shown that KRG has otoprotective properties against gentamicin [9,10] , 3-nitropropionic acid [12] , and CDDP-induced ototoxicity [8,13] . These studies revealed that KRG mainly works by inhibition of some proapoptotic genes such as caspase-1, caspase-3, and the TNF family of genes and by enhancement of antiapoptotic gene expression such as bcl-2 [8][9][10][11][12][13] .…”

“…KRG has been found to be effective in various problems that cause hearing loss such as gentamycin ototoxicity, age-related hearing loss, or 3-nitropropionic acid-induced cochlear damage [8][9][10][11][12] . CDDP-induced hearing loss has been studied in one in vitro and in one in vivo study [8,13] . The aim of this study was to evaluate the effects of different doses of KRG on CDDP ototoxicity both in vitro and in vivo.…”