Effects of C-phycocyanin and Spirulina on Salicylate-Induced Tinnitus, Expression of NMDA Receptor and Inflammatory Genes

Juen-Haur Hwang,Jin-Cherng Chen,Yin-Ching Chan,Alfred Lewin

doi:10.1371/journal.pone.0058215

Abstract

Effects of C-phycocyanin (C-PC), the active component of Spirulina platensis water extract on the expressions of N-methyl D-aspartate receptor subunit 2B (NR2B), tumor necrosis factor–α (TNF-α), interleukin-1β (IL-1β), and cyclooxygenase type 2 (COX-2) genes in the cochlea and inferior colliculus (IC) of mice were evaluated after tinnitus was induced by intraperitoneal injection of salicylate. The results showed that 4-day salicylate treatment (unlike 4-day saline treatment) caused a significant increase in NR2B, TNF-α, and IL-1β mRNAs expression in the cochlea and IC. On the other hand, dietary supplementation with C-PC or Spirulina platensis water extract significantly reduced the salicylate-induced tinnitus and down-regulated the mRNAs expression of NR2B, TNF-α, IL-1β mRNAs, and COX-2 genes in the cochlea and IC of mice. The changes of protein expression levels were generally correlated with those of mRNAs expression levels in the IC for above genes.

Highlights

Tinnitus can be perceived in one or both ears or in the head in the absence of acoustic stimulation
We aim to investigated whether C-PC or spirulina platensis water extract could reduce the tinnitus score and expression levels of NR subtype 2B (NR2B), tumor necrosis factor –a (TNF-a), IL-1b, and cyclooxygenase type 2 (COX-2) genes in the cochlea and inferior colliculus (IC) in response to intraperitoneal injections of salicylate
Salicylate-induced tinnitus was associated with up-expression of NR2B, TNF-a, and IL-1b genes [5,6] and with enzymatic inhibition of COX [4]

Summary

Introduction

Tinnitus can be perceived in one or both ears or in the head in the absence of acoustic stimulation. The prevalence of chronic tinnitus is estimated between 10.1% to 14.5% in adult population [1], and increased with age [2]. High doses of salicylate (250–300 mg/kg sodium Salicylate, i.p.) are known to reduce otoacoustic emissions, elevate hearing thresholds, and reliably induce tinnitus [3,4,5,6]. Tinnitus may arise from an increase in excitatory neurotransmission, and was associated with N-methyl D-aspartate receptor (NMDA receptor, NR) activity [4]. Our study group found that mRNA expression levels of the NR subtype 2B (NR2B) gene, tumor necrosis factor –a (TNF-a) and interleukine-1b (IL-1b) genes were elevated significantly in the cochlea and in the inferior colliculus (IC) in salicylate-induced tinnitus [5,6]. We suggested that the proinflammatory cytokines might lead to tinnitus directly or via modulating NR gene expression [5,6]

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