Eksioglu Umit, Atilgan Hasan Ikbal, Yakin Mehmet, Yazihan Nuray, Altiparmak Ugur Emrah, Yumusak Nihat, Korkmaz Meliha, Demir Ayten, Ornek Firdevs, Aribal Ayral Pelin, Koca Gokhan
a Department of Ophthalmology , Ankara Training and Research Hospital of University of Health Sciences , Ankara , Turkey.
b Department of Nuclear Medicine , Mustafa Kemal University, Faculty of Medicine , Turkey.
Cutan Ocul Toxicol. 2019 Mar;38(1):18-24. doi: 10.1080/15569527.2018.1498507. Epub 2018 Sep 11.
To evaluate antioxidant effects of active vitamin D (calcitriol) against high-dose radioiodine (RAI) therapy-associated damage of lacrimal gland.
Wistar albino rats were used and divided into three groups randomly (n = 12/group). The first group was appointed as the negative control group and received no RAI or medication. The second group was appointed as the positive control group that only received 3 mCi/kg (111 MBq/kg) RAI via gastric gavage and the last group was the treatment group that received 3 mCi/kg RAI via same method and calcitriol (200 ng/kg/day) via intraperitoneal administration. Seven days after RAI administration, bilateral intraorbital (IG), extraorbital (EG) and Harderian (HG) glands were removed for the evaluations of histopathologic, tissue cytokine, total oxidant status (TOS) and total antioxidant status (TAS).
RAI led to significant increase in tissue TOS, TNF-α, IL-6 levels and significant decrease in IL-10 and TAS levels (p < 0.05 for each). Addition of adjunctive calcitriol reversed all these parameters significantly (p < 0.05 for each).The following histopathologic parameters were seen more frequently in positive control group than the other groups: Abnormal lobular pattern, perivascular infiltration, periductal infiltration, lipofuscin-like accumulation, acinar atrophy, periductal and periacinar fibrosis in all lacrimal gland types (p < 0.05), acinar fibrosis in EG (p = 0.049), periductal fibrosis in EG and HG (p = 0.049 and 0.038, respectively), abnormal cell outlines in EG and HG (p = 0.020 and 0.011, respectively) and variation in cell size in the IG and the HG (p = 0.003 and 0.049 respectively).
RAI caused significant oxidative stress and inflammation in lacrimal glands. Vitamin D demonstrated potent anti-inflammatory, antioxidant and radio-protective effects on lacrimal glands in histopathologic, tissue cytokine and oxidant/antioxidant level evaluations.
评估活性维生素D(骨化三醇)对大剂量放射性碘(RAI)治疗相关泪腺损伤的抗氧化作用。
使用Wistar白化大鼠并随机分为三组(每组n = 12)。第一组作为阴性对照组,未接受RAI或药物治疗。第二组作为阳性对照组,仅通过灌胃给予3 mCi/kg(111 MBq/kg)RAI,最后一组为治疗组,通过相同方法给予3 mCi/kg RAI并通过腹腔注射给予骨化三醇(200 ng/kg/天)。RAI给药7天后,摘除双侧眶内(IG)、眶外(EG)和哈德氏(HG)腺,用于组织病理学、组织细胞因子、总氧化剂状态(TOS)和总抗氧化剂状态(TAS)的评估。
RAI导致组织TOS、TNF-α、IL-6水平显著升高,IL-10和TAS水平显著降低(各p < 0.05)。添加辅助性骨化三醇可显著逆转所有这些参数(各p < 0.05)。以下组织病理学参数在阳性对照组中比其他组更频繁出现:所有泪腺类型的小叶模式异常、血管周围浸润、导管周围浸润、脂褐素样积聚、腺泡萎缩、导管周围和腺泡周围纤维化(p < 0.05),EG中的腺泡纤维化(p = 0.049),EG和HG中的导管周围纤维化(分别为p = 0.049和0.038),EG和HG中的细胞轮廓异常(分别为p = 0.020和0.011)以及IG和HG中的细胞大小变化(分别为p = 0.003和0.049)。
RAI在泪腺中引起显著的氧化应激和炎症。在组织病理学、组织细胞因子和氧化剂/抗氧化剂水平评估中,维生素D对泪腺表现出强大的抗炎、抗氧化和放射保护作用。