Ginsenoside Rg1 attenuates cisplatin-induced ototoxicity in guinea pigs via Akt/Nrf2 pathway / 中草药

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.

Ligustrazine fought against cisplatin induced ototoxicity in guinea pigs / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the protective effect of Ligustrazine Injection (LI) against cisplatin-induced ototoxicity and to explore its mechanism.</p><p><b>METHODS</b>Thirty healthy adult guinea pigs were randomly divided into three groups, 10 in each group, i.e., the normal control group, the cisplatin group, and the LI group. Guinea pigs in the normal control group were intraperitoneally injected with normal saline at 3 mL/kg for 7 consecutive days. Those in the cisplatin group were intraperitoneally injected with cisplatin at 3 mg/kg for 7 consecutive days. Those in the LI group were intraperitoneally injected with LI at 140 mg/kg for 7 days, but cisplatin (3 mg/kg) was intraperitoneally injected from the opposite side starting from the 4th day. Brainstem auditory evoked potential (BAEP) was performed in all animals before and after injection. All animals were sacrificed after the final testing under anesthesia and their cochleas collected. Half the cochleas of each group were collected for silver nitrate staining of cochlear basilar membrane stretched. The other half the cochleas of each group made into paraffin sections to observe the apoptosis of cochlea cells by TUNEL method and the expression levels of c-Jun detected by immunohistochemistry.</p><p><b>RESULTS</b>There was no statistical difference in the difference of BAEP threshold among the 3 groups before injection (P > 0.05), but the BAEP threshold increased in the cisplatin group and the LI group (P < 0.05). Besides, it was higher in the cisplatin group (P < 0.05). In the cisplatin group, most hair cells were missing, spiral ganglion cells obviously decreased, more TUNEL positive cells occurred, and the expression of c-Jun was stronger. But the aforesaid impairment in the LI group was obviously lessened (P < 0.05).</p><p><b>CONCLUSIONS</b>LI showed certain antagonist effect on cisplatin-induced ototoxicity. Its mechanism might be associated with scavenging oxygen radicals of the cochlea tissue, improving the microcirculation, and fighting against apoptosis.</p>

A comparative study of the influence of different bowtie of 64 multi-slice CT on cardiac image quality and radiation dosage / 中华放射学杂志

0.05 indicating no statistical difference.However,the noise measurements for the L and C groups were 30.05 and 27.80,respectively,with P