Abstract
IntroductionOtotoxicity is a health problem appearing after powerful treatments in serious health conditions. It is sometimes inevitable when treatment of the serious disease is required. Cisplatin is an antineoplastic agent which was investigated previously to reveal increased nitrogen and reactive oxygen radicals that damages hair cells, resulting in ototoxicity. N-acetylcysteine, previously shown to decrease ototoxicity caused by different agents, is known to be a powerful in vitro antioxidant. Probably N-acetylcysteine, in addition to its antioxidant effect, blocks a cascade where reactive oxygen species result in apoptosis in the cochlea. ObjectivesThe possible preventive effect of N-acetylcysteine in cisplatin ototoxicity was studied with auditory brain stem responses, otoacoustic emissions, and histopathological investigation of the cochlea in a scanning electron microscopy. MethodsThis study was conducted on 21 Wistar Albino rats in four groups. 1mL/kg/day three times in total intraperitoneal (i.p.) Saline (n=5), 500mg/kg/day i.p. three times in total N-acetylcysteine (n=5), i.p. 15mg/kg cisplatin alone (single dose) (n=5) and i.p. 15mg/kg cisplatin plus 500mg/kg/day N-acetylcysteine (n=6) were administered. The rats were anesthetized to study the hearing tests before and after the experiment. The rats were sacrificed to investigate the cochleas by scanning electron microscopy. ResultsAuditory brain stem responses and otoacoustic emissions values were attenuated in the cisplatin group. The group that received N-acetylcysteine in addition to cisplatin had better auditory brain stem responses thresholds and otoacoustic emissions. The samples obtained from the cisplatin group showed surface irregularities, degeneration areas, and total or partial severe stereocilia losses. The changes were milder in the cisplatin+N-acetylcysteine group. ConclusionCisplatin ototoxicity can be detected by auditory brain stem responses and otoacoustic emissions testing in rats. N-acetylcysteine may protect the cochlear cells from histopathological changes. We concluded that N-acetylcysteine given 4h after cisplatin injection has a potential otoprotective effect against cisplatin ototoxicity. which suggests it could be used in clinical trials.
Highlights
Ototoxicity is a health problem appearing after powerful treatments in serious health conditions.1---3
The purpose of this study is to evaluate the possible protective properties of a potent antioxidant NAC against cisplatin ototoxicity which occurs through free radicals
We have shown that the Auditory Brainstem Responses (ABRs) and Otoacoustic Emissions (OAEs) values and the numbers of damaged cells did not markedly change in the group receiving cisplatin and NAC, in which those receiving cisplatin alone markedly changed
Summary
Ototoxicity is a health problem appearing after powerful treatments in serious health conditions. Cisplatin is an antineoplastic agent which was investigated previously to reveal increased nitrogen and reactive oxygen radicals that damages hair cells, resulting in ototoxicity. Cisplatin is a common antineoplastic agent that was investigated previously to reveal increased nitrogen and reactive oxygen radicals that damages hair cells resulting in ototoxicity.3---8. N-acetylcysteine is an antioxidant, which originally is a mucolytic for pulmonary treatment It is used for the diseases of the lungs, liver, heart and kidney in order to treat their toxic and ischemic injuries.[19] For example, NAC improves renal hemodynamics in rats with cisplatin-induced nephrotoxicity.[20] Probably NAC, in addition to its antioxidant effect, blocks a cascade where reactive oxygen species result in apoptosis in the cochlea.[21]
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