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实验性Wistar大鼠和比格犬内分泌腺的自发性病变。

Spontaneous lesions in endocrine glands of experimental Wistar rats and beagle dogs.

作者信息

Nataraju G J, Ranvir Ramchandra K, Kothule Viren R, Kadam Shekhar B, Ravichandra B V, Bhatnagar Upendra, Jain Mukul R

机构信息

Department of Pharmacology and Toxicology, Zydus Research Centre, Cadila Healthcare Ltd., Ahmedabad 382213, Gujarat, India.

Department of Pharmacology and Toxicology, Zydus Research Centre, Cadila Healthcare Ltd., Ahmedabad 382213, Gujarat, India.

出版信息

Exp Toxicol Pathol. 2016 Jan;68(1):1-13. doi: 10.1016/j.etp.2015.09.002. Epub 2015 Sep 26.

Abstract

A retrospective analysis was undertaken at Zydus Research Centre to understand the incidences of spontaneous lesions in endocrine glands of Wistar rats and beagle dogs. The data from a total of 841 Wistar rats (418 males and 423 females) and 144 beagle dogs (72 males and 72 females) was used from placebo/vehicle treated control group of different non-clinical toxicity studies. The lesions in various endocrine glands were classified according to the species and age of the animals at termination of study. Among the endocrine glands, the highest numbers (types) of spontaneous lesions were observed in adrenal glands followed in descending order by pituitary, thyroid, endocrine pancreas and parathyroid glands in Wistar rats. In beagle dogs, highest numbers (types) of spontaneous lesions were seen in adrenals followed by thyroid, endocrine pancreas, pituitary and parathyroid gland. In adrenal glands of Wistar rats, the incidences of cortical cell vacuolation, hemorrhages and hemangiectasis/peliosis were increased with age. Incidence of peliosis at ∼110 weeks of age was higher in female rats. Among the proliferative lesions in rats, higher incidences of cortical cell hyperplasia was observed followed by medullary hyperplasia, complex pheochromocytoma, cortical cell adenoma and cortical adenocarcinoma. In beagle dogs, the incidences of hemangiectasis and cortical cell vacuolation in adrenal glands were higher in 18-21 months aged dogs in both the sexes as compared to 10-12 months of age. In pituitary gland, the incidences of cystic changes were higher in older rats and dogs and the incidences were more in beagles as compared to rats. In thyroid glands, C-cell (parafollicular cells) hyperplasia/complex was observed more frequently in both the species. Few incidences of cystic changes were observed in parathyroid of 18-21 months aged beagle dogs. In endocrine pancreas, few incidences of islet-cell vacuolation, atrophy and hyperplasia were observed in both the species. The Islet cell hyperplasia was found to be more frequent in male rats at ∼110 weeks of age.

摘要

在Zydus研究中心进行了一项回顾性分析,以了解Wistar大鼠和比格犬内分泌腺自发性病变的发生率。使用了来自不同非临床毒性研究的安慰剂/赋形剂处理对照组的总共841只Wistar大鼠(418只雄性和423只雌性)和144只比格犬(72只雄性和72只雌性)的数据。根据研究结束时动物的物种和年龄,对各种内分泌腺的病变进行分类。在内分泌腺中,Wistar大鼠肾上腺中观察到的自发性病变数量(类型)最高,其次是垂体、甲状腺、内分泌胰腺和甲状旁腺,顺序递减。在比格犬中,肾上腺中观察到的自发性病变数量(类型)最高,其次是甲状腺、内分泌胰腺、垂体和甲状旁腺。在Wistar大鼠的肾上腺中,皮质细胞空泡化、出血和血管扩张/血囊肿的发生率随年龄增加。雌性大鼠在约110周龄时血囊肿的发生率更高。在大鼠的增殖性病变中,观察到皮质细胞增生的发生率较高,其次是髓质增生、复杂性嗜铬细胞瘤、皮质细胞腺瘤和皮质腺癌。在比格犬中,18 - 21月龄的犬肾上腺血管扩张和皮质细胞空泡化的发生率在两性中均高于10 - 12月龄的犬。在垂体中,老年大鼠和犬的囊性变化发生率较高,且比格犬的发生率高于大鼠。在甲状腺中,两种物种中C细胞(滤泡旁细胞)增生/复合体更为常见。在18 - 21月龄的比格犬甲状旁腺中观察到少数囊性变化病例。在内分泌胰腺中,两种物种中均观察到少数胰岛细胞空泡化、萎缩和增生病例。发现胰岛细胞增生在约110周龄的雄性大鼠中更为常见。

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