| Objective: To investigate the antagonist effects of sodium salicylate (NaSA) on the ototoxicity of cisplatin (CDDP) in guinea pigs. It will provide scientific basis and new idea for prevention and cure of ototoxicity of cisplatin. Methods : The experiment was divided into two procedures. First, 15△guinea pigs that were taken from 45 guinea pigs were randomly divided into three groups. Every group consists of 5 guinea pigs.①CDDP +NaSA(50 mg/kg):Every day these guinea pigs were peritoneal injected with 4 mg/kg cisplatin and 50 mg/kg sodium salicylate ,and were peritoneal injected with 50 mg/kg sodium salicylate again after 5 hours.②CDDP +NaSA(100 mg/kg): Every day these guinea pigs were peritoneal injected with 4 mg/kg cisplatin and 100 mg/kg sodium salicylate ,and were peritoneal injected with 100 mg/kg sodium salicylate again after 5 hours.③CDDP +NaSA(150 mg/kg):Every day these guinea pigs were peritoneal injected with 4 mg/kg cisplatin and 150 mg/kg sodium salicylate ,and were peritoneal injected with 150 mg/kg sodium salicylate again after 5 hours.Above-mentioned medicines were peritoneal injected for 6 successive days. On the seventh day, auditory brainstem response (ABR) was used to evaluate effects of the 15△guinea pigs'right ears on hearing threshold after they had been anesthetized with 40 mg/kg continal(2%) in sound isolation room.To analyze the hearing thresholds of their right ears,and it may be thought that 100 mg/kg sodium salicylate can antagonize ototoxicity of 4mg/kg cisplatin in guinea pigs in these dosages of 50 mg/kg, 100 mg/kg and 150 mg/kg, and the dosage of 100 mg/kg was used as sodium salicylate's dosage in the second procedure of the experiment. Second:The other 30guinea pigs of 45 guinea pigs were randomly divided into two groups. Every group consists of 15 guinea pigs.⑴CDDP+NaSA: Every day these guinea pigs were peritoneal injected with 4mg/kg cisplatin and 100 mg/kg sodium salicylate ,and were peritoneal injected with 100 mg/kg sodium salicylate again after 5 hours.⑵CDDP +NS(control group): Every day these guinea pigs were peritoneal injected with 4 mg/kg cisplatin and 100 mg/kg physiologic saline (NS) ,and were peritoneal injected with 100 mg/kg physiologic saline again after 5 hours. Above mentioned medicines were peritoneal injected for 6 successive days. On the seventh day, auditory brainstem response(ABR) was used to evaluate effects of the 30guinea pigs'right ears on hearing threshold in sound isolation room after they had been anesthetized with 40 mg/kg continal(2%). Then distortion product otoacoustic emission (DPOAE) was monitored to observe DPOAE amplitudes of their right ears , and analyzed the changes of amplitude of DPOAE before and after treatment. 10 guinea pigs that were randomly taken from each group were quickly decapitated in order to take their serum and cochleas after their DPOAE amplitudes had been monitored by DPOAE. Changes of superoxide dismutase (SOD) and malondialdehyde (MDA) content were observed in serum and cochleas. The other 10 guinea pigs of 30guinea pigs were quickly decapitated in order to take their right cochleas, and these cochleas were made for paraffin section preparatio of cochleas that were observed with light microscope. Results: 1. In the first procedure of the experiment : The threshold of ABR of the①group was significantly higher than before drug (P <0.01).The threshold of ABR the②group and the③group were insignificantly different from before drug (P >0.05);After drug, the threshold of ABR of the②group was insignificantly different from the other two groups (P >0.05), but the threshold of ABR of the①group was significantly higher than the③group (P <0.05). To analyze these indicatrixes, and it may think that 100 mg/kg sodium salicylate can antagonize the ototoxicity of 4 mg/kg cisplatin in guinea pigs in these dosages of 50 mg/kg, 100 mg/kg and 150 mg/kg, and the dosage of 100 mg/kg was used as sodium salicylate's dosage in the second procedure of the experiment. In the second procedure of the experiment: The threshold of ABR was significantly higher in the control group than before drug (P <0.01); The threshold of ABR was insignificantly different in the⑴group from before drug (P >0.05); After drug, The threshold of ABR of the⑴group was significantly lower than in the control group (P <0.01). 2. At identical frequency , the DPOAE amplitudes were significantly lower than before drug at the frequencies of 1,2,3, 4,6 and 8 kHz in the⑴group and the control group (P <0.01). After drug,The amplitudes of DPOAE at1, 2, 4, 6 and 8 kHz in the⑴group were higher than those in control group (1 kHz, P <0.05;2, 4, 6, 8 kHz,P <0.01), but difference at 3 kHz between two groups was not significant (P >0.05). 3. The content of MDA in serum was significantly lower in the⑴group than in the control group (P <0.05). The vitality of SOD in serum was significantly higher in the⑴group than in the control group (P <0.01). 4. The content of MDA in cochlea tissue was significantly lower in the⑴group than in the control group (P <0.01).The vitality of SOD in cochlea tissue was significantly higher in the⑴group than in the control group (P <0.01). 5.The light microscope showed that the structural damage of hair cells was serious in the control group,while the structural damage of hair cells was slighter in the⑴group than that in the control group. Conclusion: Sodium salicylate has protective effect on cochlea of Guinea pigs against ototoxicity of cisplatin. |
