Ginsenoside Rg1 attenuates cisplatin-induced ototoxicity in guinea pigs via Akt/Nrf2 pathway
10.7501/j.issn.0253-2670.2018.14.017
- Author:
Xian-Chang SUN
1
Author Information
1. Department of Physiology, Taishan Medical University
- Publication Type:Journal Article
- Keywords:
Cisplatin;
Ginsenoside Rg1;
Nrf2;
Ototoxicity;
Reactive oxygen species
- From:
Chinese Traditional and Herbal Drugs
2018;49(14):3309-3317
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the protective effects of Ginsenoside Rg1 against cisplatin (CDDP)-induced ototoxicity and its mechanisms. Methods: Eighty guinea pigs were randomly divided into five groups with ten rats in each group, namely control group, cisplatin group, 5 mg/kg Rg1 + CDDP group, 10 mg/kg Rg1 + CDDP group, and 20 mg/kg Rg1 + CDDP group. Animals in the control group were administered with normal saline (NS, 3 mL/kg) via intraperitoneal (ip) route for 7 consecutive days. Cisplatin group were injected with cisplatin alone (3 mg/kg, ip) for 7 consecutive days. Rg1 + CDDP groups were given 3 consecutive days of Rg1 (5 mg/kg, 10 mg/kg, and 20 mg/kg ip respectively for each group) ahead of the application of Rg1 + cisplatin (3 mg/kg, ip) for 7 consecutive days. For the 7 consecutive days of co-treatment of Rg1 with cisplatin, Rg1 was injected peritoneally 1 hour before the injection of CDDP at the contralateral side. Auditory brainstem response (ABR) test was used to evaluate the auditory function of rats in each group before and after administration of CDDP. Stretched preparation of cochlear basilar membrane was examined for morphological changes of outer hair cells (OHC). The general case of diet, loss of hair, and activity status of guinea pigs were observed every day. HE staining techniques and optical microscopy were used to evaluate the lesions of spiral ganglion neurons (SGN). The levels of malondiadehyde (MDA) and superoxidedismutase (SOD) activities in cochlear tissues were detected by biochemical assay kits. The protein expressions of Caspase-3, p53, p-Akt, and Nrf2 were determined by western blotting. Results: Compared with CDDP group, Rg1 co-treatment significantly lowered the CDDP-induced ABR threshold elevation (P < 0.05) in a dose dependent manner. The severe damages of cochlear OHCs and SGNs exhibited in CDDP group were also markedly attenuated by co-treatment with Rg1 in the Rg1 + CDDP groups. In CDDP group, the MDA levels were significantly increased while the SOD activity was decreased in cochlear tissue after CDDP injection. Rg1 treatment evidently reduced the level of MDA and enhanced the SOD activity (P < 0.05). Western blot results indicated that Rg1 treatment significantly attenuated CDDP-induced pro-apoptotic protein expressions (Capase-3 and p53). Furthermore, treatment with Rg1 resulted in an increased expression of p-Akt and intranuclear Nrf2 in cochlear tissue compared to the CDDP group. Conclusion: Ginsenoside Rg1 protects auditory functions from cisplatin-induced ototoxicity via the Akt/Nrf-2 pathway in guinea pigs.
