The Protective Effect Of Salvia Miltiorrhiza On Cisplatin Ototoxicity

Objectives: Cisplatin is one of chemotherapeutic medicines which are mainly used to cure the malignant tumor in urogenital system and head-neck. But it has side effects on inner ear. The mechanism of cisplatin Ototoxicity remains unclear.Recently, there is some findings that support nitric oxide mediates cisplatin Ototoxicity. Nitric oxide plays an important role in the physiological reaction of tissue and cells. On physiological conditions, the function is maintaining the blood flow of cochlea and transmiting the neural message by nitric oxide. On pathological conditions, when inducible nitric oxide synthase is actived, there is a large amount of nitric oxide produced. Those productions can damage the normal cells and tissue, furthermore, it affect cell metabolism and functions. Nitric oxide synthase is the speed-limiting enzyme for the production of nitric oxide. Recent study demonstrated that there is nitric oxide synthase in inner hair cells,out hair cells and spiral ganglion cells. With the development of modern study people pay much attention to inducible nitric oxide synthase, it may has a high correlation with cisplatin Ototoxicity. In order to know the role of nitric oxide in the mechanism of cisplatin Ototoxicity, we used auditorybrainstem response examation, light microscope, immmunohistochemistry, electron microscope and image quantative analysis technique to investigate the expression of inducible nitric oxide synthase in cochlea of guinea pigs after the injection of cisplatin and salvia miltiorrhiza. The study also aims at proving the protective effect of salvia miltiorrhiza on cisplatin ototoxicity and providing the appendix treatment measure for the therapy of tumor.Material and Methods: Thirty two white guinea pigs with normal hearing were randomly divided into three groups,including a control group, an experimental group and an inhibited group. The control group consisted of 11 guinea pigs,treated with ip injections of physiological saline for 5 conseutive days, in a dialy dosage of Iml-kg The experimental group comprised 10 guinea pigs received cisplatin 2mg-kg-1 per day ip for 5 consecutive days. And the inhibited group include 11 guinea pigs that received combined treatment with cisplatin 2mg-kg-1 and salvia miltiorrhiza 8ml-kg. The salvia miltiorrhiza was injected to abdominal cavity on the first and second day solely. On the third , the fifth and the seventh day ,the salvia miltiorrhiza was used just after the cisplatin injected an hour later. Alternations of hearing function were evaluatd by examination for auditory brainstem response and latency of wave I. The changes of tissue and cells in cochlea were observed by light and electron microscope. Then all the guinea pigs were killed by brokenneck just after the final examination of auditory brainstem response was completed. The cochleas were removed and laid in different fixatives. The specimens were sent for immunohistochemistry and electron microscope respectively after different disposals. Finally we used the image -quantative analysis system to exame the expression of inducible nitric oxide synthase.Results: The results showed that auditory brainstem response thresholds elevated and the latency of wave I delayed significantly in experimental group. But in the inhibited group , the threshold of ABR and latency of wave I was reduced. The threshold of ABR and latency of wave I was normal in control group. The threshold of ABR and latency of wave I in the experimental and inhibited group, compared with both of which did not administrate any medicine, there were statistically significant difference(P<0.01,P<0.05, respectively). The comparsion between the experimental and the inhibited group is obvious, by t test (P<0.01)The results of light microscope indicated that the damage to corti organ in inhibited group was slighter than the experimental group. Under immunohistochemical staining, there was intense immunohistochemistical staining to iNOS in inner hair cells, out hair cells and spiral ganglion cells of cochlea in...