顺铂对耳蜗血管纹毒性作用的研究
|
摘要
目的探讨顺铂对内耳血管纹的毒性机制。方法使用在体小鼠模型,用记录内淋巴电位的方法,研究使用顺铂是否可以迅速影响内淋巴电位的幅度。用离体培养的小鼠的血管纹中间细胞,记录中间细胞的膜电位,观察顺铂是否能够影响中间细胞胞膜上离子泵的转运能力和离子通道的通透性。结果在实验动物中注射顺铂后并不能改变其内淋巴电位的幅度。在培养的中间细胞上观察到,灌流顺铂对细胞静息膜电位没有影响。结论使用顺铂一个疗程后出现的内淋巴电位降低,并不是通过对血管纹上离子通道或离子泵的影响引起的,顺铂对血管纹的功能不能造成急性损伤。
Objective To determine mechanisms of cisplatin toxicity to stria vascularis in adult mice. A recent study has showed that cisplatin retains in the stria vascularis for a long period of time and is detrimental to stria function. Our goal is to determine whether cisplatin toxicity to stria is mediated by blocking Na+/K+-ATPase, Na+/K+/2 Cl-cotransporter and K+ channels in the cell membrane of stria cells. Methods Endocochlear potential was measured using the sharp electrode technique when cisplatin was administrated to the tail vein in adult mice. Whole-cell patch-clamp technique was used to measure membrane potential from cultured melanocytes prepared from neonatal mice. Results We showed that there was no significant reduction of endocochlear potential within 30 minutes after cisplatin was administrated to the circulation. In contrast, significant reduction of endocochlear potential was observed within seconds after hypoxia. Cisplatin administration also did not lead to change of the resting membrane potential of cultured melanocytes. Conclusion While cisplatin is detrimental to stria function, it appears that its toxicity is not mediated by blocking Na+/K+-ATPase, Na+/K+/2 Cl-cotransporter and K+channels in the cell membrane of the three types of cells in the stria. It is likely that cisplatin may damage stria morphology and function through mechanisms of oxidative stress and DNA damage, similar to those that cause loss of cochlear hair cells.
Objective To determine mechanisms of cisplatin toxicity to stria vascularis in adult mice. A recent study has showed that cisplatin retains in the stria vascularis for a long period of time and is detrimental to stria function. Our goal is to determine whether cisplatin toxicity to stria is mediated by blocking Na+/K+-ATPase, Na+/K+/2 Cl-cotransporter and K+ channels in the cell membrane of stria cells. Methods Endocochlear potential was measured using the sharp electrode technique when cisplatin was administrated to the tail vein in adult mice. Whole-cell patch-clamp technique was used to measure membrane potential from cultured melanocytes prepared from neonatal mice. Results We showed that there was no significant reduction of endocochlear potential within 30 minutes after cisplatin was administrated to the circulation. In contrast, significant reduction of endocochlear potential was observed within seconds after hypoxia. Cisplatin administration also did not lead to change of the resting membrane potential of cultured melanocytes. Conclusion While cisplatin is detrimental to stria function, it appears that its toxicity is not mediated by blocking Na+/K+-ATPase, Na+/K+/2 Cl-cotransporter and K+channels in the cell membrane of the three types of cells in the stria. It is likely that cisplatin may damage stria morphology and function through mechanisms of oxidative stress and DNA damage, similar to those that cause loss of cochlear hair cells.
引文
1 Sheth S,Mukherjea D,Rybak LP,et al.Mechanisms of cisplatin induced ototoxicity and otoprotection[J].Front Cell Neurosci,2017,11:338.
2 Callejo A,Sedó-Cabezón L,Juan ID,et al.Cisplatin-induced ototoxicity:Effects,mechanisms and protection strategies[J].Toxics,2015,3(3):268-293.
3 Ganesan P,Schmiedge J,Manchaiah V,et al.Ototoxicity:A challenge in diagnosis and treatment[J].J Audiol Otol,2018,22(2):59-68.
4 Steyger PS,Cunningham LL,Esquivel CR,et al.Editorial:Cellular mechanisms of ototoxicity[J].Front Cell Neurosci,2018,12:75.
5 Ding D,Allman BL,Salvi R.Review:ototoxic characteristics of platinum antitumor drugs[J].Anat Rec(Hoboken),2012,295(11):1851-67.
6 Breglio AM,Rusheen AE,Shide ED,et al.Cisplatin is retained in the cochlea indefinitely following chemotherapy[J].Nat Commun,2017,8(1):1654.
7 Konishi T,Mendelsohn M.Effect of ouabain on cochlear potentials and endolymph composition in guinea pigs[J].Acta Otolaryngol(Stockh),1970,69(3):192-199.
8 Kusakari J,Comegys TH,Thalmann I,et al.Effect of ethacrynic acid,furosemide,and ouabain upon the endolymphatic potential and upon high energy phosphates of the stria vascularis[J].Laryngoscope,1978,88(1):12-37.
9 Nin F,Hibino H,Doi K,et al.The endocochlear potential depends on two K+diffusion potentials and an electrical barrier in the stria vascularis of the inner ear[J].Proc Natl Acad Sci USA,2008,105(5):1751-1756.
10 Ciarimboli G.Membrane transporters as mediators of cisplatin side-effects[J].Anticancer Res,2014,34(1):547-550.
11 Prado WA,Corrado AP,Marseillan RF.Competitive antagonism between calcium and antibiotics at the neuromuscular junction[J].Arch Int Pharmacodyn Ther,1978,231(2):297-307.
12 Kroese AB,Das A,Hudspeth AJ.Blockage of the transduction channels of hair cells in the bullfrog’s sacculus by aminoglycoside antibiotics[J].Hear Res,1989,37(3):203-217
13 Lin X,Hume RI,Nuttall AL.Voltage-dependent block by neomycin of the ATP-induced whole cell current of guinea-pig outer hair cells[J].J Neurophysiol,1993,70(4):1593-1605.
14 Blanchet C,Erostegui C,Sugasawa M,Dulon D.Gentamicin blocks ACh-evoked K+current in guinea-pig outer hair cells by impairing Ca2+entry at the cholinergic receptor[J].J Physiol,2000,525(Pt 3):641-654
15 Hibino H,Horio Y,Inanobe A,et al.An ATP-dependent inwardly rectifying potassium channel,KAB-2(Kir4.1)in cochlear stria vascularis of inner ear:its specific subcellular localization and correlation with the formation of endocochlear potential[J].J Neurosci,1997,17(12):4711-4721
16 Woolf NK,Ryan AF,Harris JP.Development of mammalian endocochlear potential:normal ontogeny and effects of anoxia[J].Am J Physiol,1986,250(3 Pt 2):R493-498.
17李轶,刘会占,龚树生,等.耳蜗毛细胞与血管纹的相互依存关系的研究[J].中华耳科学杂志,2014,12(3):475-480.Li Y,Liu HZ,Gong SS,et al,Relationship between the survival of the organ of corti and stria vascularis[J].Chinese Journal of Otology,2014,12(3):475-480.
18 Zhang Q,Liu H,Soukup GA,et al.Identifying microRNAs involved in aging of the lateral wall of the cochlear duct[J].PLoSOne,2014,9(11):e112857.
19 Liu H,Li Y,Chen L,et al.Organ of Corti and Stria Vascularis:Is there an Interdependence for Survival?[J].PLoS One,2016,11(12):e0168953.
20谢鼎华.基础与应用听力学概要[M].湖南科学技术出版社,2016,202-220.Xie DH.Summary of Basic and Applied Audiology[M].Hunan Science and Technology Press,2016,202-220.
21丁大连,金晓杰.利尿酸致聋的豚鼠耳蜗生物电改变[J].临床耳鼻咽喉科杂志,1996,10(6):330-332.Ding DL,Jing XL.Cochlear bioelectrical changes in guinea pigs with diuretic acid-induced deafness[J].Journal of Clinical Otorhinolarynglolgy Head and Neck Surgery,1996,10(6):330-332.
22 Dallos P,Schoeny ZG,Cheatham MA.Cochlear summating potentials:composition[J].Science,1970,170(3958):641-644.
23 Dallos P,Santos-Sacchi J,Flock A.Intracellular recordings from cochlear outer hair cells[J].Science,1982,218(4572):582-584.
24 Russell IJ.Origin of the receptor potential in inner hair cells of the mammalian cochlea--evidence for Davis'theory[J].Nature,1983,301(5898):334-336.
25丁大连,吴大正.缺氧豚鼠耳蜗功能与结构的改变[J].中华耳鼻咽喉科杂志,1993,28(5):265-267.Ding DL,Wu DZ.Changes of cochlear function and structure in hypoxic guinea pigs[J].Chinese Journal of Otology,1993,28(5):265-267.
26丁大连,曲雁,亓卫东,等.缺氧性内耳损害[J].中华耳科学杂志,2008,6(4):468-474.Ding DL,Qu Y,Qi WD,et al.Hypoxic inner ear damage[J].Chinese Journal of Otology,2008,6(4):468-474.
27 Hamers FP,Wijbenga J,Wolters FL,et al.Cisplatin ototoxicity involves organ of Corti,stria vascularis and spiral ganglion:modulation by alpha MSH and ORG 2766[J].Audiol Neurootol,2003,8(6):305-315.
28丁大连,亓卫东,张梅,等.顺铂及其耳毒性[J].中华耳科学杂志,2008,6(2):125-133.Ding DL,Qi WD,Zhang M,et al.Cisplatin and its ototoxicity[J].Chinese Journal of Otology,2008,6(2):125-133.
29 Li Y,Ding D,Jiang H,et al.Co-administration of cisplatin and furosemide causes rapid and massive loss of cochlear hair cells in mice[J].Neurotox Res.2011,20(4):307-319.
30 Ding D,Wang P,Jiang H,et al.Gene expression in cisplatin ototoxicity and protection with p53 inhibitor[J].Journal of Otology.2009,4(2):61-70
31 Shimizu T,Lee EL,Ise T,et al.Volume-sensitive Cl(-)channel as a regulator of acquired cisplatin resistance[J].Anticancer Res,2008,8(1A):75-83
32 Laurell G,Ekborn A,Viberg A,et al.Effects of a single high dose of cisplatin on the melanocytes of the stria vascularis in the guinea pig[J].Audiol Neurootol,2007,12(3):170-178.
33 Tsukasaki N,Whitworth CA,Rybak LP.Acute changes in cochlear potentials due to cisplatin[J].Hear Res,2000,149(1-2):189-198.
34 Meech RP,Campbell KC,Hughes LP,et al.A semiquantitative analysis of the effects of cisplatin on the rat stria vascularis[J].Hear Res,1998,124(1-2):44-59.
35 Suzuki M,Kaga K.Effect of cisplatin on the negative charge barrier in strial vessels of the guinea pig.A transmission electron microscopic study using polyethyleneimine molecules[J].Eur Arch Otorhinolaryngol,1996,253(6):351-355.
36 Laurell G,Teixeira M,Sterkers O,et al.Effect of cisplatin administration on the electrochemical composition of endolymph in the rat cochlea[J].Hear Res,1995,87(1-2):16-20.
37 Kohn S,Fradis M,Podoshin L,et al.Endothelial injury of capillaries in the stria vascularis of guinea pigs treated with cisplatin and gentamicin[J].Ultrastruct Pathol,1997,21(3):289-299.
38 Tange RA,Vuzevski VD.Changes in the stria vascularis of the guinea pig due to cisplatinum[J].Arch Otorhinolaryngol,1984,239(1):41-47.
39 Ding D,Jiang H,Wang P,et al.Cell death after co-administration of cisplatin and ethacrynic acid[J].Hear Res.2007,226(1-2):129-139.
40 Ding D,McFadden SL,Woo JM,et al.Ethacrynic acid rapidly and selectively abolishes blood flow in vessels supplying the lateral wall of the cochlea[J].Hear Res.2002,173(1-2):1-9.
41丁大连,蒋海燕.利尿酸是打开血-迷路屏障的钥匙[J].中华耳科学杂志,2004,2(1):42-47.Ding DL,Jiang HY.Diuric acid is the key to opening the blood-labyrinth barrier[J].Chinese Journal of Otology,2004,2(1):42-47.
42 Liu H,Pecka JL,Zhang Q,et al.Characterization of transcriptomes of cochlear inner and outer hair cells[J].J Neurosci,2014,34(33):11085-11095.
43 Liu H,Chen L,Giffen KP,et al.Cell-specific transcriptome analysis shows that adult pillar and Deiters'cells express genes encoding machinery for specializations of cochlear hair cells[J].Front Mol Neurosci,2018,11:356.
44 Li Y,Liu H,Giffen KP,et al.Transcriptomes of cochlear inner and outer hair cells from adult mice[J].Sci Data,2018,5:180199.
2 Callejo A,Sedó-Cabezón L,Juan ID,et al.Cisplatin-induced ototoxicity:Effects,mechanisms and protection strategies[J].Toxics,2015,3(3):268-293.
3 Ganesan P,Schmiedge J,Manchaiah V,et al.Ototoxicity:A challenge in diagnosis and treatment[J].J Audiol Otol,2018,22(2):59-68.
4 Steyger PS,Cunningham LL,Esquivel CR,et al.Editorial:Cellular mechanisms of ototoxicity[J].Front Cell Neurosci,2018,12:75.
5 Ding D,Allman BL,Salvi R.Review:ototoxic characteristics of platinum antitumor drugs[J].Anat Rec(Hoboken),2012,295(11):1851-67.
6 Breglio AM,Rusheen AE,Shide ED,et al.Cisplatin is retained in the cochlea indefinitely following chemotherapy[J].Nat Commun,2017,8(1):1654.
7 Konishi T,Mendelsohn M.Effect of ouabain on cochlear potentials and endolymph composition in guinea pigs[J].Acta Otolaryngol(Stockh),1970,69(3):192-199.
8 Kusakari J,Comegys TH,Thalmann I,et al.Effect of ethacrynic acid,furosemide,and ouabain upon the endolymphatic potential and upon high energy phosphates of the stria vascularis[J].Laryngoscope,1978,88(1):12-37.
9 Nin F,Hibino H,Doi K,et al.The endocochlear potential depends on two K+diffusion potentials and an electrical barrier in the stria vascularis of the inner ear[J].Proc Natl Acad Sci USA,2008,105(5):1751-1756.
10 Ciarimboli G.Membrane transporters as mediators of cisplatin side-effects[J].Anticancer Res,2014,34(1):547-550.
11 Prado WA,Corrado AP,Marseillan RF.Competitive antagonism between calcium and antibiotics at the neuromuscular junction[J].Arch Int Pharmacodyn Ther,1978,231(2):297-307.
12 Kroese AB,Das A,Hudspeth AJ.Blockage of the transduction channels of hair cells in the bullfrog’s sacculus by aminoglycoside antibiotics[J].Hear Res,1989,37(3):203-217
13 Lin X,Hume RI,Nuttall AL.Voltage-dependent block by neomycin of the ATP-induced whole cell current of guinea-pig outer hair cells[J].J Neurophysiol,1993,70(4):1593-1605.
14 Blanchet C,Erostegui C,Sugasawa M,Dulon D.Gentamicin blocks ACh-evoked K+current in guinea-pig outer hair cells by impairing Ca2+entry at the cholinergic receptor[J].J Physiol,2000,525(Pt 3):641-654
15 Hibino H,Horio Y,Inanobe A,et al.An ATP-dependent inwardly rectifying potassium channel,KAB-2(Kir4.1)in cochlear stria vascularis of inner ear:its specific subcellular localization and correlation with the formation of endocochlear potential[J].J Neurosci,1997,17(12):4711-4721
16 Woolf NK,Ryan AF,Harris JP.Development of mammalian endocochlear potential:normal ontogeny and effects of anoxia[J].Am J Physiol,1986,250(3 Pt 2):R493-498.
17李轶,刘会占,龚树生,等.耳蜗毛细胞与血管纹的相互依存关系的研究[J].中华耳科学杂志,2014,12(3):475-480.Li Y,Liu HZ,Gong SS,et al,Relationship between the survival of the organ of corti and stria vascularis[J].Chinese Journal of Otology,2014,12(3):475-480.
18 Zhang Q,Liu H,Soukup GA,et al.Identifying microRNAs involved in aging of the lateral wall of the cochlear duct[J].PLoSOne,2014,9(11):e112857.
19 Liu H,Li Y,Chen L,et al.Organ of Corti and Stria Vascularis:Is there an Interdependence for Survival?[J].PLoS One,2016,11(12):e0168953.
20谢鼎华.基础与应用听力学概要[M].湖南科学技术出版社,2016,202-220.Xie DH.Summary of Basic and Applied Audiology[M].Hunan Science and Technology Press,2016,202-220.
21丁大连,金晓杰.利尿酸致聋的豚鼠耳蜗生物电改变[J].临床耳鼻咽喉科杂志,1996,10(6):330-332.Ding DL,Jing XL.Cochlear bioelectrical changes in guinea pigs with diuretic acid-induced deafness[J].Journal of Clinical Otorhinolarynglolgy Head and Neck Surgery,1996,10(6):330-332.
22 Dallos P,Schoeny ZG,Cheatham MA.Cochlear summating potentials:composition[J].Science,1970,170(3958):641-644.
23 Dallos P,Santos-Sacchi J,Flock A.Intracellular recordings from cochlear outer hair cells[J].Science,1982,218(4572):582-584.
24 Russell IJ.Origin of the receptor potential in inner hair cells of the mammalian cochlea--evidence for Davis'theory[J].Nature,1983,301(5898):334-336.
25丁大连,吴大正.缺氧豚鼠耳蜗功能与结构的改变[J].中华耳鼻咽喉科杂志,1993,28(5):265-267.Ding DL,Wu DZ.Changes of cochlear function and structure in hypoxic guinea pigs[J].Chinese Journal of Otology,1993,28(5):265-267.
26丁大连,曲雁,亓卫东,等.缺氧性内耳损害[J].中华耳科学杂志,2008,6(4):468-474.Ding DL,Qu Y,Qi WD,et al.Hypoxic inner ear damage[J].Chinese Journal of Otology,2008,6(4):468-474.
27 Hamers FP,Wijbenga J,Wolters FL,et al.Cisplatin ototoxicity involves organ of Corti,stria vascularis and spiral ganglion:modulation by alpha MSH and ORG 2766[J].Audiol Neurootol,2003,8(6):305-315.
28丁大连,亓卫东,张梅,等.顺铂及其耳毒性[J].中华耳科学杂志,2008,6(2):125-133.Ding DL,Qi WD,Zhang M,et al.Cisplatin and its ototoxicity[J].Chinese Journal of Otology,2008,6(2):125-133.
29 Li Y,Ding D,Jiang H,et al.Co-administration of cisplatin and furosemide causes rapid and massive loss of cochlear hair cells in mice[J].Neurotox Res.2011,20(4):307-319.
30 Ding D,Wang P,Jiang H,et al.Gene expression in cisplatin ototoxicity and protection with p53 inhibitor[J].Journal of Otology.2009,4(2):61-70
31 Shimizu T,Lee EL,Ise T,et al.Volume-sensitive Cl(-)channel as a regulator of acquired cisplatin resistance[J].Anticancer Res,2008,8(1A):75-83
32 Laurell G,Ekborn A,Viberg A,et al.Effects of a single high dose of cisplatin on the melanocytes of the stria vascularis in the guinea pig[J].Audiol Neurootol,2007,12(3):170-178.
33 Tsukasaki N,Whitworth CA,Rybak LP.Acute changes in cochlear potentials due to cisplatin[J].Hear Res,2000,149(1-2):189-198.
34 Meech RP,Campbell KC,Hughes LP,et al.A semiquantitative analysis of the effects of cisplatin on the rat stria vascularis[J].Hear Res,1998,124(1-2):44-59.
35 Suzuki M,Kaga K.Effect of cisplatin on the negative charge barrier in strial vessels of the guinea pig.A transmission electron microscopic study using polyethyleneimine molecules[J].Eur Arch Otorhinolaryngol,1996,253(6):351-355.
36 Laurell G,Teixeira M,Sterkers O,et al.Effect of cisplatin administration on the electrochemical composition of endolymph in the rat cochlea[J].Hear Res,1995,87(1-2):16-20.
37 Kohn S,Fradis M,Podoshin L,et al.Endothelial injury of capillaries in the stria vascularis of guinea pigs treated with cisplatin and gentamicin[J].Ultrastruct Pathol,1997,21(3):289-299.
38 Tange RA,Vuzevski VD.Changes in the stria vascularis of the guinea pig due to cisplatinum[J].Arch Otorhinolaryngol,1984,239(1):41-47.
39 Ding D,Jiang H,Wang P,et al.Cell death after co-administration of cisplatin and ethacrynic acid[J].Hear Res.2007,226(1-2):129-139.
40 Ding D,McFadden SL,Woo JM,et al.Ethacrynic acid rapidly and selectively abolishes blood flow in vessels supplying the lateral wall of the cochlea[J].Hear Res.2002,173(1-2):1-9.
41丁大连,蒋海燕.利尿酸是打开血-迷路屏障的钥匙[J].中华耳科学杂志,2004,2(1):42-47.Ding DL,Jiang HY.Diuric acid is the key to opening the blood-labyrinth barrier[J].Chinese Journal of Otology,2004,2(1):42-47.
42 Liu H,Pecka JL,Zhang Q,et al.Characterization of transcriptomes of cochlear inner and outer hair cells[J].J Neurosci,2014,34(33):11085-11095.
43 Liu H,Chen L,Giffen KP,et al.Cell-specific transcriptome analysis shows that adult pillar and Deiters'cells express genes encoding machinery for specializations of cochlear hair cells[J].Front Mol Neurosci,2018,11:356.
44 Li Y,Liu H,Giffen KP,et al.Transcriptomes of cochlear inner and outer hair cells from adult mice[J].Sci Data,2018,5:180199.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |