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The effect of L-NAME on hearing loss induced by TNF-a and IL1 injected into CSF in guinea pigs

The effect of L-NAME on hearing loss induced by TNF-a and IL1 injected into CSF in guinea pigs,10.1016/j.otohns.2004.06.280,Otolaryngology-head and Ne

The effect of L-NAME on hearing loss induced by TNF-a and IL1 injected into CSF in guinea pigs  
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Problem: One of the most serious complications of bacterial meningitis, particularly in childhood, is sensorineural hearing loss; yet the mechanism of this hearing loss is not clearly understood. It is also known that the levels of TNF-¥á and IL-1¥â in CSF are significantly elevated in bacterial meningitis patients. This study was designed to evaluate the role of nitric oxide (NO) in the ototoxic effect of TNF-¥á and IL-1¥â and L-NAME injected into the CSF of guinea pigs.Methods: Twenty-six guinea pigs (52 ears) were randomly assigned into 6 groups consisting of control group, L-NAME group, TNF-¥á group, TNF-¥á + L-NAME group, IL-1¥â group, and IL-1¥â + L-NAME group.The thresholds of auditory brain stem response (ABR) were measured before as well as 6 and 24 hours after the administration of the cytokines. TNF-¥á and IL-1¥â were directly injected into the cisterna magna in a dosage of 0.1 ¥ı̀ g in 10 ¥ı̀g/ml concentration. L-NAME, NO synthase inhibitor, was injected intraperitoneally 30 minutes prior to the administration of cytokines. Scanning electron microscopy (SEM) was used to find the morphological damage of hair cells.Results: In TNF-¥á group, the ABR threshold at 6 and 24 hours after the injection was 19.2¡3410.2 dB, 18.3¡3410.3 dB; in the TNF-¥á + L-NAME group, 3.3¡342.6 dB and 8.3¡344.1 dB; in the IL-1¥â group, 6.9¡344.6 dB and 11.25¡348.3 dB; in the IL-1¥â + L-NAME group, 1.7¡342.7 dB and 1.3¡342.5 dB, respectively. The outer hair cell damage in the second and third rows was noted in the TNF-¥á and IL-1¥â groups.Conclusion: This study suggests that the sensorineural hearing loss associated with bacterial meningitis may be caused in part by the actions of proinflammatory cytokines such as TNF-¥á and IL-1¥â. The hearing loss may be mediated by NO and it can be prevented by L-NAME.Significance: Hearing loss induced by bacterial meningitis can be prevented partly by L-NAME.Support: None reported.
Journal: Otolaryngology-head and Neck Surgery - OTOLARYNGOL HEAD NECK SURG , vol. 131, no. 2, pp. P162-P163, 2004
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