Abstract

BackgroundIn addition to the direct effects of irradiation, the induced inflammatory response may play an important role in the damage to the inner ear caused by radiotherapy for the treatment of head and neck cancers. Resolvin E1 (RvE1) has anti-inflammatory activity, acting by reducing neutrophil infiltration and proinflammatory cytokine expression. Therefore, in this study we sought to confirm whether the inflammation induced by irradiation was involved in damage to the inner ear after radiotherapy and to investigate the protective effect and underlying mechanism of RvE1 using mouse models.MethodsA dose of RvE1 was delivered by intraperitoneal injection to mice before irradiation. Changes in the auditory brainstem response (ABR), relative balance ability, inner ear morphology and the expression levels of inflammatory factors in the inner ear were analyzed on days 7 and 14 after irradiation and compared among different experimental groups.ResultsChanges of ABR and relative balance ability showed the inner functions of experimental mice presented severe damage after irradiation, but the damage was significantly alleviated after RvE1 pretreatment compared to irradiation alone. Morphological analysis of the inner ear showed severe damage to the cochlea and vestibule after irradiation. In contrast, damage to the cochlea and vestibule was significantly reduced in the RvE1-pretreated group compared to that in the irradiation alone group. Along with these functional and morphological changes, the mRNA expression level of anti-inflammatory factors interleukin-2 was significantly increased, while those of proinflammatory factors interleukin-6 and tumor necrosis factor-α were significantly decreased in the inner ear of mice after RvE1 pretreatment compared to irradiation alone.ConclusionsWe believe that inflammation induced by irradiation is involved in the damage to the inner ear caused by radiotherapy, and that RvE1 reduces the damage caused by irradiation to the inner ear by regulating the induced inflammatory response.

Highlights

  • Head and neck cancer is one of the most common malignancies

  • Resolvin E1 (RvE1) alone has no effects on the inner ear Six mice from each of the Sham/Wild type group (WT), RvE1, ray irradiation group (Rad) and Rad+RvE1 groups were selected for auditory brainstem response (ABR) and roller tests, morphological analysis and the detections of inflammatory factors on days 7 and 14 of the experiments

  • The results suggested that RvE1 might protect the inner ear from irradiation damage by regulating the inflammatory response induced by irradiation, which was associated with these inflammatory factors

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Summary

Introduction

Head and neck cancer is one of the most common malignancies. According to epidemiological surveys, the annual incidence of head and neck cancer in China is 15.22/100,000, which accounts for 4.45% of all cases of malignant tumors. Our previous clinical study found an abnormal increase of interleukin (IL)-6 in the peripheral blood of patients with irradiation-induced inner ear damage [9], and another study found that a large number of inflammatory cells appeared in the vestibular tissue of irradiated guinea pigs [10]. These studies imply that the inflammation induced by irradiation may play an important role in damage to the inner ear, but there is a lack of complete experimental evidence in support of this hypothesis. In addition to the direct effects of irradiation, the induced inflammatory response may play an important role in the damage to the inner ear caused by radiotherapy for the treatment of head and neck cancers. In this study we sought to confirm whether the inflammation induced by irradiation was involved in damage to the inner ear after radiotherapy and to investigate the protective effect and underlying mechanism of RvE1 using mouse models

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