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依达拉奉对小鼠肠道损伤具有保护作用,且不干扰辐射的抗肿瘤效应。

Edaravone Exerts Protective Effects on Mice Intestinal Injury without Interfering with the Anti-Tumor Effects of Radiation.

作者信息

Kawamoto Terufumi, Sasai Keisuke

机构信息

Department of Radiation Oncology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan.

出版信息

Curr Issues Mol Biol. 2023 Jun 28;45(7):5362-5372. doi: 10.3390/cimb45070340.

Abstract

The appropriate dosage of edaravone-a radioprotective agent-and its effect on tumors are unknown. This study evaluated the effects of edaravone on intestinal injuries and tumors in mice induced by whole body X-ray irradiation. Small intestinal mucositis was induced in C3H/HeNSlc mice using a single X-ray dose (15 Gy). Edaravone (15, 30, and 100 mg/kg) was administered 30 min before irradiation to evaluate its protective effect. After 3.5 days, the jejunum was removed and the histological changes were evaluated. Next, C3H/HeNSlc mice with squamous cell carcinoma VII tumors were provided the same single X-ray dose and 100 mg/kg edaravone; further, the tumors were immediately induced after irradiation. The tumor cell viability was detected using an in vivo-in vitro colony formation assay. We found that the intestinal colony-forming ability after irradiation was significantly higher in the 100 mg/kg edaravone group than that in the control group. Moreover, the apoptotic cells in the villi immunohistochemically stained with cleaved caspase-3 were significantly lower in the 100 mg/kg edaravone group than in the control group. We found no radioprotective effects of intraperitoneally inoculated edaravone in both hind legs on squamous cell carcinoma VII tumors. These findings suggest that 100 mg/kg edaravone exerts protective effects on small intestinal injuries without interfering with the antitumor effects of radiation.

摘要

依达拉奉(一种辐射防护剂)的合适剂量及其对肿瘤的影响尚不清楚。本研究评估了依达拉奉对全身X射线照射诱导的小鼠肠道损伤和肿瘤的影响。使用单次X射线剂量(15 Gy)在C3H/HeNSlc小鼠中诱导小肠黏膜炎。在照射前30分钟给予依达拉奉(15、30和100 mg/kg)以评估其保护作用。3.5天后,取出空肠并评估组织学变化。接下来,给患有VII型鳞状细胞癌肿瘤的C3H/HeNSlc小鼠给予相同的单次X射线剂量和100 mg/kg依达拉奉;此外,在照射后立即诱导肿瘤。使用体内-体外集落形成试验检测肿瘤细胞活力。我们发现,100 mg/kg依达拉奉组照射后的肠道集落形成能力显著高于对照组。此外,100 mg/kg依达拉奉组中用裂解的半胱天冬酶-3免疫组化染色的绒毛中的凋亡细胞明显低于对照组。我们发现腹腔内接种于双后肢的依达拉奉对VII型鳞状细胞癌肿瘤没有辐射防护作用。这些发现表明,100 mg/kg依达拉奉对小肠损伤具有保护作用,而不干扰辐射的抗肿瘤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cf4/10378466/65225fb735ef/cimb-45-00340-g001.jpg

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