Flufenamic acid prevents behavioral manifestations of salicylate-induced tinnitus in the rat

Bal, Ramazan; Üstündağ, Yasemin; Bulut, Funda; Demir, Caner Feyzi; Bal, Ali

doi:10.5114/aoms.2016.57597

Cited by 6 publications

(3 citation statements)

References 46 publications

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“…It suppresses the overall excitability of neurons by decreasing the spontaneous firing rate. In addition, TRPM7 is also an important regulator of cellular Zn 2+ which plays an antioxidant role under stressful conditions 29,30 .…”

Section: Resultsmentioning

confidence: 99%

Investigation of Some Ion Channel Expressions in Cochlear Nucleus of Tinnitus Induced Rats

Üstündağ,

Dinç,

Bal

2024

İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi

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Aim: The aim of this study is to gain a better understanding of how certain ion channels play a role in the molecular mechanisms of salicylate- and noise-induced tinnitus. Method: The present study was conducted on thirty-two, 4-month-old, male Wistar Albino rats. Rats were equally divided into four groups; two experimental groups and two control groups. The assessment of tinnitus was based on a behavioral test which was modified from the conditional suppression method. Tinnitus was induced by sodium salicylate administration and noise exposure in rats in which the suppression ratios were zero (0). All animals in both experimental and control groups were decapitated in deep anaesthesia for 2 h after salicylate or saline administration and noise exposure, consecutively. Tissues from the left and right cochlear nucleus were dissected immediately in ice-cold RNA later (Invitrogen). Before reverse transcription, the RNA pools were arranged. Quantitative changes in HCN1, HCN2, HCN4, SCN1A, SCN2A1, SCN3A, TRPM2, TRPM7 and GAPDH mRNA expressions in the cochlear nucleus in both experimental and control groups were examined by quantitative real-time PCR method. Statistical data were analysed using the SPSS 21 program (Version 21.0, SPSS Inc., Chicago, IL, USA) with the Kruskal-Wallis and Mann-Whitney U tests. Results: Fold changes in the expression levels of SCNA1, SCN2A1, SCN3A, TRPM2, TRPM7, CACNA1B, HCN1, HCN2 and HCN4 genes in both salicylate-induces tinnitus (SAT) and noise-induced tinnitus (NT) groups compared with the control group. According to these data, it is seen that the mRNA levels of all genes are lower in the cochlear nucleus area of the rats in both SAT and NT groups than in the control group. Considering each of these genes in NT group: SCNA1, SCN3A, TRPM7 genes slightly decreased; SCN2A1, TRPM2, HCN1 and HCN4 genes slightly increased compared with the SAT group. For HCN2 gene fold changes were nearly the same in the NT and SAT groups. Conclusion: The findings of this study suggest that tinnitus generation may be closely related to alterations in several key ion channel families activity including voltage-gated calcium channels, hyperpolarization-activated cyclic nucleotide–gated (HCN) channels, transient receptor potential (TRP) channels, voltage-gated sodium channels within the CN, specifically in response to salicylate-induced and noise-induced tinnitus models.

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Section: Resultsmentioning

confidence: 99%

Investigation of Some Ion Channel Expressions in Cochlear Nucleus of Tinnitus Induced Rats

Üstündağ,

Dinç,

Bal

2024

İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi

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“…Caspase-dependent cell death pathways are predominant in women [ 47 ], whereas oxidative stress-dependent activation and apoptosis inducing factor stimulation of poly (ADP-ribose) polymerase (PARP) are involved in men [ 48 , 49 ]. Bal et al [ 50 ] reported that inactivating TRPM2 ion channels would modulate the neuronal activity in the central audio path by reducing neural excitability, presumed to cause an increase in inhibitory signals in auditory nuclei leading to decreased tinnitus-producing signals. This suggests that a brain-protective mechanism against apoptosis in our menopausal group may work to prevent the apoptotic cascade by inhibiting TRPM2.…”

Section: Discussionmentioning

confidence: 99%

The decrease in hippocampal transient receptor potential M2 (TRPM2) channel and muscarinic acetylcholine receptor 1 (CHRM1) is associated with memory loss in a surgical menopause rat model

et al. 2021

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The aim of the study was to investigate the association of transient receptor potential M2 (TRPM2) channel and muscarinic acetylcholine receptor 1 (CHRM1) activity with the memorial functions that are deteriorated in surgical menopause. Material and methods: A total of 14 female rats were randomly divided into 2 groups: group (G)1: sham group; group (G)2: surgical menopause group, the group in which bilateral ovariectomy was performed. Fourteen days after the surgical procedure, learning and memorial tests were performed in G1 and G2 for a totally 13 days. The time required for the rats to find the cheese in the labyrinth was recorded and statistical evaluation of it was performed between groups. On the 14 th day of the memory test, the rats were decapitated and the brain tissues were fixed in 10% formalin. Hippocampal TRPM2 and CHRM1 gene expression was evaluated with RNA isolation, complementary DNA (cDNA) synthesis and quantitative real-time PCR (qRT-PCR) analysis. TRPM2 and CHRM1 immunoreactivity was evaluated in hippocampal tissue with the immunohistochemical method. Histo-score was calculated regarding the diffuseness of and severity of the staining; and statistical analyses were performed. Results: In the ovariectomized group, the mean time required for the rats to find the cheese was statistically significantly elongated (39.29 ±4.0 s vs. 29.86 ±2.6 s). When the hippocampal TRPM2 and CHRM1 gene expression and immunoreactivity were compared with the sham group, there was a statistically significant decrease in the surgical menopause group (p < 0.05). Conclusions: In surgical menopause, in deterioration of memorial functions, hippocampal TRPM2 channel and CHRM1 activity plays an important role.

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“…These features were earlier observed in response to aspirin and sodium salicylate, because salicylate was soon thought to be the active compound. Sodium salicylate-induced tinnitus is the most widely used animal model to study tinnitus in rats ( 1 – 3 , 38 ). In previous studies, BDNF was found to play a key role in the onset and the persistence of salicylate-induced tinnitus ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Long-term Administration of Salicylate-induced Changes in BDNF Expression and CREB Phosphorylation in the Auditory Cortex of Rats

Shi

et al. 2018

Otology &Amp; Neurotology

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Hypothesis:We investigated whether salicylate induces tinnitus through alteration of the expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, tyrosine kinase receptor B (TrkB), cAMP-responsive element-binding protein (CREB), and phosphorylated CREB (p-CREB) in the auditory cortex (AC).Background:Salicylate medication is frequently used for long-term treatment in clinical settings, but it may cause reversible tinnitus. Salicylate-induced tinnitus is associated with changes related to central auditory neuroplasticity. Our previous studies revealed enhanced neural activity and ultrastructural synaptic changes in the central auditory system after long-term salicylate administration. However, the underlying mechanisms remained unclear.Methods:Salicylate-induced tinnitus-like behavior in rats was confirmed using gap prepulse inhibition of acoustic startle and prepulse inhibition testing, followed by comparison of the expression levels of BDNF, proBDNF, TrkB, CREB, and p-CREB. Synaptic ultrastructure was observed under a transmission electron microscope.Results:BDNF and p-CREB were upregulated along with ultrastructural changes at the synapses in the AC of rats treated chronically with salicylate (p < 0.05, compared with control group). These changes returned to normal after 14 days of recovery (p > 0.05).Conclusion:Long-term administration of salicylate increased BDNF expression and CREB activation, upregulated synaptic efficacy, and changed synaptic ultrastructure in the AC. There may be a relationship between these factors and the mechanism of tinnitus.

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Flufenamic acid prevents behavioral manifestations of salicylate-induced tinnitus in the rat

Cited by 6 publications

References 46 publications

Investigation of Some Ion Channel Expressions in Cochlear Nucleus of Tinnitus Induced Rats

Investigation of Some Ion Channel Expressions in Cochlear Nucleus of Tinnitus Induced Rats

The decrease in hippocampal transient receptor potential M2 (TRPM2) channel and muscarinic acetylcholine receptor 1 (CHRM1) is associated with memory loss in a surgical menopause rat model

Long-term Administration of Salicylate-induced Changes in BDNF Expression and CREB Phosphorylation in the Auditory Cortex of Rats

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