Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Research Article

Cisplatin Toxicology: The Role of Pro-inflammatory Cytokines and GABA Transporters in Cochlear Spiral Ganglion

Author(s): Dongmei Gao, Hong Yu, Bo Li, Li Chen, Xiaoyu Li* and Wenqing Gu*

Volume 25, Issue 45, 2019

Page: [4820 - 4826] Pages: 7

DOI: 10.2174/1381612825666191106143743

Price: $65

Abstract

Background: The current study was conducted to examine the specific activation of pro-inflammatory cytokines (PICs), namely IL-1β, IL-6 and TNF-α in the cochlear spiral ganglion of rats after ototoxicity induced by cisplatin. Since γ-aminobutyric acid (GABA) and its receptors are involved in pathophysiological processes of ototoxicity, we further examined the role played by PICs in regulating expression of GABA transporter type 1 and 3 (GAT-1 and GAT-3), as two essential subtypes of GATs responsible for the regulation of extracellular GABA levels in the neuronal tissues.

Methods: ELISA and western blot analysis were employed to examine the levels of PICs and GATs; and auditory brainstem response was used to assess ototoxicity induced by cisplatin.

Results: IL-1β, IL-6 and TNF-α as well as their receptors were significantly increased in the spiral ganglion of ototoxic rats as compared with sham control animals (P<0.05, ototoxic rats vs. control rats). Cisplatin-ototoxicity also induced upregulation of the protein levels of GAT-1 and GAT-3 in the spiral ganglion (P<0.05 vs. controls). In addition, administration of inhibitors to IL-1β, IL-6 and TNF-α attenuated amplification of GAT-1 and GAT-3 and improved hearing impairment induced by cisplatin.

Conclusion: Our data indicate that PIC signals are activated in the spiral ganglion during cisplatin-ototoxicity which thereby leads to upregulation of GABA transporters. As a result, it is likely that de-inhibition of GABA system is enhanced in the cochlear spiral ganglion. This supports a role for PICs in engagement of the signal mechanisms associated with cisplatin-ototoxicity, and has pharmacological implications to target specific PICs for GABAergic dysfunction and vulnerability related to cisplatin-ototoxicity.

Keywords: Cytokine, GABA, cochlear spiral ganglion, ototoxicity, cisplatin, TNF-α.

« Previous Next »
[1]
Allen NJ, Káradóttir R, Attwell D. Reversal or reduction of glutamate and GABA transport in CNS pathology and therapy. Pflugers Arch 2004; 449(2): 132-42.
[http://dx.doi.org/10.1007/s00424-004-1318-x] [PMID: 15338308]
[2]
Altun Z, Olgun Y, Ercetin P, et al. Protective effect of acetyl-l-carnitine against cisplatin ototoxicity: role of apoptosis-related genes and pro-inflammatory cytokines. Cell Prolif 2014; 47(1): 72-80.
[http://dx.doi.org/10.1111/cpr.12080] [PMID: 24286513]
[3]
Arnold T, Oestreicher E, Ehrenberger K, Felix D. GABA(A) receptor modulates the activity of inner hair cell afferents in guinea pig cochlea. Hear Res 1998; 125(1-2): 147-53.
[http://dx.doi.org/10.1016/S0378-5955(98)00144-0] [PMID: 9833968]
[4]
Bauer CA, Brozoski TJ, Holder TM, Caspary DM. Effects of chronic salicylate on GABAergic activity in rat inferior colliculus. Hear Res 2000; 147(1-2): 175-82.
[http://dx.doi.org/10.1016/S0378-5955(00)00130-1] [PMID: 10962183]
[5]
Borden LA. GABA transporter heterogeneity: pharmacology and cellular localization. Neurochem Int 1996; 29(4): 335-56.
[http://dx.doi.org/10.1016/0197-0186(95)00158-1] [PMID: 8939442]
[6]
Callejo A, Sedó-Cabezón L, Juan ID, Llorens J. Cisplatin-induced ototoxicity: Effects, mechanisms and protection strategies. Toxics 2015; 3(3): 268-93.
[http://dx.doi.org/10.3390/toxics3030268] [PMID: 29051464]
[7]
Conti F, Minelli A, Melone M. GABA transporters in the mammalian cerebral cortex: localization, development and pathological implications. Brain Res Brain Res Rev 2004; 45(3): 196-212.
[http://dx.doi.org/10.1016/j.brainresrev.2004.03.003] [PMID: 15210304]
[8]
Fujioka M, Kanzaki S, Okano HJ, Masuda M, Ogawa K, Okano H. Proinflammatory cytokines expression in noise-induced damaged cochlea. J Neurosci Res 2006; 83(4): 575-83.
[http://dx.doi.org/10.1002/jnr.20764] [PMID: 16429448]
[9]
Harrison RT, DeBacker JR, Bielefeld EC. A low-dose regimen of cisplatin before high-dose cisplatin potentiates ototoxicity. Laryngoscope 2015; 125(2): E78-83.
[http://dx.doi.org/10.1002/lary.24948] [PMID: 25267530]
[10]
Jin XT, Galvan A, Wichmann T, Smith Y. Localization and function of GABA transporters GAT-1 and GAT-3 in the basal ganglia. Front Syst Neurosci 2011; 5: 63.
[http://dx.doi.org/10.3389/fnsys.2011.00063] [PMID: 21847373]
[11]
Juhn SK, Rybak LP. Labyrinthine barriers and cochlear homeostasis. Acta Otolaryngol 1981; 91(5-6): 529-34.
[http://dx.doi.org/10.3109/00016488109138538] [PMID: 6791457]
[12]
Kaur T, Mukherjea D, Sheehan K, Jajoo S, Rybak LP, Ramkumar V. Short interfering RNA against STAT1 attenuates cisplatin-induced ototoxicity in the rat by suppressing inflammation. Cell Death Dis 2011; 2: e180.
[http://dx.doi.org/10.1038/cddis.2011.63] [PMID: 21776018]
[13]
Keithley EM, Wang X, Barkdull GC. Tumor necrosis factor alpha can induce recruitment of inflammatory cells to the cochlea, Otology & neurotology: official publication of the American Otological Society, American neurotology society. Euro Acad Otol Neurotol 2008; 29: 854-9.
[http://dx.doi.org/10.1097/MAO.0b013e31818256a9]
[14]
Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 2007; 7(8): 573-84.
[http://dx.doi.org/10.1038/nrc2167] [PMID: 17625587]
[15]
Kim J, Cho HJ, Sagong B, et al. Alpha-lipoic acid protects against cisplatin-induced ototoxicity via the regulation of MAPKs and proinflammatory cytokines. Biochem Biophys Res Commun 2014; 449(2): 183-9.
[http://dx.doi.org/10.1016/j.bbrc.2014.04.118] [PMID: 24796665]
[16]
Ladrech S, Wang J, Simonneau L, Puel JL, Lenoir M. Macrophage contribution to the response of the rat organ of Corti to amikacin. J Neurosci Res 2007; 85(9): 1970-9.
[http://dx.doi.org/10.1002/jnr.21335] [PMID: 17497672]
[17]
Mahgoub E, Kumaraswamy SM, Kader KH, et al. Genipin attenuates cisplatin-induced nephrotoxicity by counteracting oxidative stress, inflammation, and apoptosis. Biomed Pharmacother 2017; 93: 1083-97.
[18]
Maison SF, Rosahl TW, Homanics GE, Liberman MC. Functional role of GABAergic innervation of the cochlea: phenotypic analysis of mice lacking GABA(A) receptor subunits alpha 1, alpha 2, alpha 5, alpha 6, beta 2, beta 3, or delta. J Neurosci 2006; 26(40): 10315-26.
[http://dx.doi.org/10.1523/JNEUROSCI.2395-06.2006] [PMID: 17021187]
[19]
Murashita H, Tabuchi K, Sakai S, Uemaetomari I, Tsuji S, Hara A. The effect of a GABAA agonist muscimol on acoustic injury of the mouse cochlea. Neurosci Lett 2007; 418(1): 18-21.
[http://dx.doi.org/10.1016/j.neulet.2007.02.060] [PMID: 17353094]
[20]
Okano T, Nakagawa T, Kita T, et al. Bone marrow-derived cells expressing Iba1 are constitutively present as resident tissue macrophages in the mouse cochlea. J Neurosci Res 2008; 86(8): 1758-67.
[http://dx.doi.org/10.1002/jnr.21625] [PMID: 18253944]
[21]
Overstreet LS, Westbrook GL. Synapse density regulates independence at unitary inhibitory synapses. J Neurosci 2003; 23(7): 2618-26.
[http://dx.doi.org/10.1523/JNEUROSCI.23-07-02618.2003] [PMID: 12684447]
[22]
Ravi R, Somani SM, Rybak LP. Mechanism of cisplatin ototoxicity: antioxidant system. Pharmacol Toxicol 1995; 76(6): 386-94.
[http://dx.doi.org/10.1111/j.1600-0773.1995.tb00167.x] [PMID: 7479581]
[23]
Reijntjes DOJ, Pyott SJ. The afferent signaling complex: regulation of type I spiral ganglion neuron responses in the auditory periphery. Hear Res 2016; 336: 1-16.
[http://dx.doi.org/10.1016/j.heares.2016.03.011] [PMID: 27018296]
[24]
Richerson GB, Wu Y. Dynamic equilibrium of neurotransmitter transporters: not just for reuptake anymore. J Neurophysiol 2003; 90(3): 1363-74.
[http://dx.doi.org/10.1152/jn.00317.2003] [PMID: 12966170]
[25]
Sakai S, Tabuchi K, Murashita H, Hara A. Activation of the GABA(A) receptor ameliorates the cochlear excitotoxicity caused by kainic acid in the guinea pig. Tohoku J Exp Med 2008; 215(3): 279-85.
[http://dx.doi.org/10.1620/tjem.215.279] [PMID: 18648188]
[26]
Semyanov A, Walker MC, Kullmann DM, Silver RA. Tonically active GABA A receptors: modulating gain and maintaining the tone. Trends Neurosci 2004; 27(5): 262-9.
[http://dx.doi.org/10.1016/j.tins.2004.03.005] [PMID: 15111008]
[27]
Sheth S, Mukherjea D, Rybak LP, Ramkumar V. Mechanisms of cisplatin-induced ototoxicity and otoprotection. Front Cell Neurosci 2017; 11: 338.
[http://dx.doi.org/10.3389/fncel.2017.00338] [PMID: 29163050]
[28]
So H, Kim H, Lee JH, et al. Cisplatin cytotoxicity of auditory cells requires secretions of proinflammatory cytokines via activation of ERK and NF-kappaB. J Assoc Res Otolaryngol 2007; 8(3): 338-55.
[http://dx.doi.org/10.1007/s10162-007-0084-9] [PMID: 17516123]
[29]
Tan BT, Lee MM, Ruan R. Bone-marrow-derived cells that home to acoustic deafened cochlea preserved their hematopoietic identity. J Comp Neurol 2008; 509(2): 167-79.
[http://dx.doi.org/10.1002/cne.21729] [PMID: 18461607]
[30]
Tang X, Zhu X, Ding B, Walton JP, Frisina RD, Su J. Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse. Neuroscience 2014; 259: 184-93.
[http://dx.doi.org/10.1016/j.neuroscience.2013.11.058] [PMID: 24316061]
[31]
Tange RA, Vuzevski VD. Changes in the stria vascularis of the guinea pig due to cis-platinum. Arch Otorhinolaryngol 1984; 239(1): 41-7.
[http://dx.doi.org/10.1007/BF00454261] [PMID: 6537883]
[32]
Wakabayashi K, Fujioka M, Kanzaki S, et al. Blockade of interleukin-6 signaling suppressed cochlear inflammatory response and improved hearing impairment in noise-damaged mice cochlea. Neurosci Res 2010; 66(4): 345-52.
[http://dx.doi.org/10.1016/j.neures.2009.12.008] [PMID: 20026135]
[33]
Wang X, Truong T, Billings PB, Harris JP, Keithley EM. Blockage of immune-mediated inner ear damage by etanercept, otology & neurotology: official publication of the American otological society, American neurotology society. Euro Acad Otol Neurotol 2003; 24: 52-7.
[http://dx.doi.org/10.1097/00129492-200301000-00012]
[34]
Wu Y, Wang W, Díez-Sampedro A, Richerson GB. Nonvesicular inhibitory neurotransmission via reversal of the GABA transporter GAT-1. Neuron 2007; 56(5): 851-65.
[http://dx.doi.org/10.1016/j.neuron.2007.10.021] [PMID: 18054861]

Rights & Permissions Print Cite
Article Metrics
41
1
World Health Day
© 2024 Bentham Science Publishers | Privacy Policy