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A Study on the Antagonist Effects of Sodium Salicylate on the Ototoxicity of Cisplatin in Guinea Pigs

Author: WangXueLing
Tutor: LiWanRong
School: Luzhou Medical College
Course: Otolaryngology
Keywords: Cisplatin Sodium salicylate Ototoxicity Auditory brainstem response Distortion product otoacoustic emissions
CLC: R764
Type: Master's thesis
Year: 2007
Downloads: 57
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Abstract


Objective: To investigate the salicylic acid sodium (sodium salicylate, NaSA) against the ototoxicity of cisplatin (cisplatin, CDDP) role is to provide scientific basis for clinical the ototoxicity CISPLATIN on new ideas. Methods: The experimental procedure is divided into two steps. I. The first step taken in the 45 guinea pigs the 15 △ guinea pigs were randomly divided into three groups, n = 5: the 1 of CDDP NaSA (50 mg / kg): simultaneous injection of intraperitoneal cisplatin 4 mg / kg and salicylaldehyde sodium 50 mg / kg and an interval of 5 hours after the second injection of sodium salicylate, the same doses. ② CDDP NaSA (100 mg / kg): the simultaneous injection of intraperitoneal cis the platinum 4 mg / kg and sodium salicylate 100 mg / kg, interval 5 hours after the second injection of sodium salicylate, the same doses. ③ CDDP NaSA (150 mg / kg): intraperitoneal simultaneous injection of cisplatin 4 mg / kg and sodium salicylate 150 mg / kg, the interval of five hours after the second injection of sodium salicylate, the same doses as before. Groups medicines continuous injection of 6 days, 7 days, 1 day withdrawal, groups of guinea pigs with 2% sodium pentobarbital 40 mg / kg intraperitoneal injection of anesthesia using auditory brainstem response in sound insulation chamber ( The auditory brainstem response, ABR) test the technology on guinea pigs, the right ear 15 △ detection observed before and after treatment in each group ABR threshold changes. From the preliminary screening the resulting indicators sodium salicylate among the three doses (100 mg / kg) in the 50 mg / kg, 100 mg / kg and 150 mg / kg to antagonize cisplatin (4 mg / kg) due to guinea pigs the ototoxic dose, and as the dose of sodium salicylate in the second-stage experimental procedure. Second, the second step, the remaining 30 guinea pigs were randomly divided into 2 groups (n = 15): ⑴ CDDP NaSA group: intraperitoneal injection of cisplatin 4 mg / kg and salicylic acid, sodium 100 mg / kg, after an interval of 5 hours 2nd injection of sodium salicylate, the same doses. ⑵ CDDP NS (control group): daily intraperitoneal simultaneous administration of cis-platinum 4 mg / kg and normal saline (physiologic saline., NS) 100 mg / kg, and the second time after an interval of 5 hours, injected with saline, the same doses as before. Groups medicines continuous injection of 6 days, 7 days or 1 day withdrawal, the two groups of guinea pigs with 2% sodium pentobarbital 40 mg / kg in sound insulation indoor anesthetized by intraperitoneal injection using auditory brainstem response testing technology detects its right ear was observed before and after treatment in each group changes in ABR threshold. Detection ABR threshold guinea pig anesthesia unawakened state in sound insulation room distortion product otoacoustic emissions (distortion product otoacoustic emission DPOAE) testing technology continues to detect its right ear, DPOAE amplitude before and after treatment groups was observed. Take 10 guinea pigs in each group were detected DPOAE amplitude rapidly decapitated and remove serum and cochlear specimens, test serum and cochlear tissue superoxide dismutase (superoxide dismutase, SOD) activity and malondialdehyde (malondialdehyde , MDA) content, observed after treatment differences between the two groups of indicators. The groups remaining five guinea pigs rapidly were decapitated after detection DPOAE amplitude remove its right ear the cochlear preparation of cochlear paraffin sections of specimens by light microscopy. Results: First, the ABR detection showed that, in the experiment the first step, before and after each group medication own control, ① The of CDDP NaSA (50 mg / kg) guinea pigs medication ABR thresholds than medication significantly with increased (P lt; 0.01), ② The of CDDP NaSA (100 mg / kg) group, and ③ of CDDP NaSA, (150 mg / kg) guinea pigs after treatment than before treatment ABR threshold slightly increased, the difference was not significant (P gt; 0.05). After treatment, ① The of CDDP NaSA (50 mg / kg) group and ③ The of CDDP NaSA (150 mg / kg) group ② CDDP NaSA (100 mg / kg) group compared to the ABR threshold value of the differences are not significant with (P gt; 0.05), while the ① CDDP NaSA (50 mg / kg) group ABR threshold was significantly greater than ③ CDDP NaSA (150 mg / kg) group (P lt; 0.05). From the preliminary screening of the above indicators sodium salicylate among the three doses (100 mg / kg) in the 50 mg / kg, 100 mg / kg and 150 mg / kg to antagonize cisplatin (4 mg / kg) due to guinea pigs the ototoxic dose, and as the dose of sodium salicylate in the second-stage experimental procedure. In the experiment the second step, each group medication before and after their own control, ⑴ of CDDP NaSA group medication ABR thresholds than medication slightly higher, the difference is not significant with (P gt; 0.05), control group medication ABR thresholds than medication significantly with l high (P lt; 0.01). ⑴ of CDDP NaSA group of ABR threshold was significantly less than the control group (P lt; 0.01) after treatment. Second, DPOAE detection ⑴ of CDDP NaSA and control groups before and after treatment self-control in the same distortion product otoacoustic emission frequency analysis, analysis 1,2,3,4,6,8 kHz frequency when the two groups DPOAE amplitude were significantly lower (P lt; 0.01). After treatment (1) of CDDP NaSA group analysis of frequency 1,2,4,6,8 kHz DPOAE amplitude was significantly greater than the control group (1 kHz, P lt; 0.05; 2, 4, 6, 8 kHz, P lt; 0.01), but the DPOAE amplitude differences of the two groups in the analysis of the frequency of 3 kHz is not significant (P gt; 0.05). Three serum MDA content and SOD activity detection (1) of CDDP NaSA serum MDA content compared with the control group was significantly lower (P lt; 0.05), serum SOD activity was significantly higher (P lt; 0.01). MDA content and SOD activity was detected in the cochlea show that (1) of CDDP NaSA group cochlea MDA content compared with the control group was significantly lower (P lt; 0.01), and the cochlear tissue SOD activity was significantly higher (P lt; 0.01). , Light microscopy showed that the outer hair cells of the control group, the extent of the damage is heavier (1) of CDDP NaSA group than the damage to the outer hair cells of the control group was significantly lighter. Conclusion: sodium salicylate on cisplatin-induced ototoxicity obvious antagonism.

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CLC: > Medicine, health > Otorhinolaryngology > Otology,ear disease
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