Expression of Inducible Nitric Oxide Synthase in the Cochlea following Immune Response in the Endolymphatic Sac of Guinea Pigs

Abstract

Immunohistochemical study for inducible nitric oxide synthase (iNOS or NOS II) in the cochlea of guinea pigs was performed after the injection of keyhole limpet hemocyanin (KLH) into the endolymphatic sac. Morphological changes were observed in the cochlea of all animals after the injection of KLH. Increased iNOS expression was detected in the lateral wall, organ of Corti and ganglion cells. It is known that high levels of nitric oxide can lead to inner ear dysfunction. Our results suggest that iNOS may mediate the inner ear disturbance as seen in endolymphatic hydrops.

Hidropsia endolinfática experimental sob ação de inibidor da óxido nítrico sintase tipo II: avaliação com emissões otoacústicas e eletrococleografia

“…Since NOS II participates in the inespecific cell mechanisms for defense and inflammation 4 , we decided to wait 2 days, thus allowing healing of the surgical wound. We do not know for sure when NOS II is synthesized, since Michel et al (2000) 8 showed this enzyme present in experimental animals at 3 weeks of the hydrops induction by a block in both the endolymphatic duct and sac, while Watanabe et al (2001) 10 showed NOS II expression already at 1 day of postop. In this last model, the authors used antigen injection in the endolymphatic sac to cause hydrops and we do not know if NOS II expression occurs at the same time in these two different induction models.…”

“…These aforementioned alterations may be responsible or may happen together with NOS II expression, with NO production damaging hair cells and also the marginal cells of the stria vascularis and over activate the ON/GMPc via with consequent cochlear microcirculation dysfunction and greater glutamate release. The latter would block neural transmission through N-metil-D-aspartato receptors 2,7,8,10,29 . Aminoguanidine was probably capable of mitigating these lesions.…”

“…NOS II has its production induced by different stimulus such as cytokines, ischemia, interferon or lipopolysaccharide, it is calcium-dependent, it is not usually expressed in the cochlea and produces NO in great amounts, about 100 to 1000 times more that NOS I and III 2,4,[5][6][7] . When produced in greater amounts and continuously, NO has neurotoxic and citotoxic effects, moreover, the former is catalyzed by NOS II 2,[7][8][9][10] . Studies in which NO donors are used, in other words, exogenous substances that release NO when metabolized, show that NO causes cell injury and loss of hair cells.…”

Nitric oxide synthase inhibitor reduces noise-induced cochlear damage in guinea pigs

“…Since NO is the resultant product of activation of NOS, it is reasonable to speculate that NOS was induced and activated by noise stimulation. High levels of NO can lead to inner ear dysfunction [9]. The excessive NO is toxic to cells by different mechanisms [10].…”

Future opportunities in preventing ototoxicity: Caffeic acid phenethyl ester may be a candidate (Review)

“…Previously, in vivo and in vitro studies have shown that cytokines increase inducible nitric oxide synthase (iNOS) production in middle ear epithelial cells (26). Intracellular NO production inhibition prevents the hypersecretion of mucin that is stimulated by ROS and other inflammatory mediators (27).…”