Mor Firdevs, Sengul Omur, Topsakal Senay, Kilic Mehmet Akif, Ozmen Ozlem
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Mehmet Akif Ersoy University, Istiklal Yerleskesi, Burdur 15030, Turkey.
Department of Endocrinology and Metabolism, Faculty of Medicine, Pamukale University, Denizli 20070, Turkey.
Toxins (Basel). 2017 Apr 19;9(4):144. doi: 10.3390/toxins9040144.
In this study, the diabetogenic effects of long term Ochratoxin A (OTA) administration in rats were investigated, and its role in the etiology of diabetes mellitus (DM) was examined utilizing 42 female Wistar rats for these purposes. The rats were divided into three different study and control groups according to the duration of the OTA administration. The rats received 45 μg OTA daily in their feed for 6, 9 and 24 weeks, respectively. Three control groups were also used for the same time periods. Blood and pancreatic tissue samples were collected during the necropsy at the end of the 6, 9 and 24 weeks. The plasma values of insulin, glucagon and glucose were determined for the study and control groups. Pancreatic lesions were evaluated via histopathological examination and insulin and glucagon expression in these lesions was subsequently determined using immunohistochemical methods. Statistically significant decreases in insulin levels were observed, in contrast to increases in blood glucagon and glucose levels. Histopathological examinations revealed slight to moderate degeneration in Langerhans islet cells in all OTA-treated groups. Immunohistochemistry of pancreatic tissue revealed decreased insulin and increased glucagon expression. This study demonstrated that OTA may cause pancreatic damage in the Langerhans islet and predispose rats to DM.
在本研究中,研究了长期给大鼠施用赭曲霉毒素A(OTA)的致糖尿病作用,并为此使用42只雌性Wistar大鼠检查了其在糖尿病(DM)病因中的作用。根据OTA给药持续时间,将大鼠分为三个不同的研究组和对照组。大鼠分别在其饲料中每日接受45μg OTA,持续6、9和24周。在相同时间段内也使用了三个对照组。在6、9和24周结束时尸检期间采集血液和胰腺组织样本。测定研究组和对照组的胰岛素、胰高血糖素和葡萄糖的血浆值。通过组织病理学检查评估胰腺病变,随后使用免疫组织化学方法确定这些病变中胰岛素和胰高血糖素的表达。与血液中胰高血糖素和葡萄糖水平升高相反,观察到胰岛素水平有统计学意义的下降。组织病理学检查显示,所有OTA处理组的胰岛细胞均有轻度至中度变性。胰腺组织免疫组织化学显示胰岛素表达降低,胰高血糖素表达增加。本研究表明,OTA可能导致胰岛的胰腺损伤,并使大鼠易患糖尿病。