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D-葡萄糖在斯普拉格-道利大鼠和叙利亚金黄地鼠中的联合慢性毒性和致癌性研究。

D-glucose combined chronic toxicity and carcinogenicity studies in Sprague-Dawley rats and Syrian golden hamsters.

作者信息

Bomhard E, Bischoff H, Mager H, Krötlinger F, Schilde B

机构信息

BAYER AG, Institute of Toxicology, Wuppertal, Germany.

出版信息

Drug Chem Toxicol. 1998 Aug;21(3):329-53. doi: 10.3109/01480549809002209.

Abstract

After an initial period of 16 weeks with increasing concentrations, D-glucose was administered at 30% in the diet to 50 male and 50 female Sprague-Dawley rats from the 17th to the 112th study week. Additional 10 male and 10 female animals were treated for 14 months and then sacrificed for interim examination. Groups of 60 male and 60 female Syrian golden hamsters received D-glucose in the form of 20% solution in tap water for a period of 80 weeks. In each case, groups consisting of an equal number of untreated animals served as controls. General behavior and mortality were not affected by the treatment. The rats and hamsters treated with glucose showed significantly higher body weights of up to a maximum of 16% in male and 26% in female rats, or 15% in male and female hamsters. In rats, the increase was evident by week 14, and in the hamsters by week 10. Glucose-dosed rats displayed a slightly increased feed intake and a reduced water intake. Both parameters, however, were not influenced in hamsters. Hematological and histopathological examination showed no pertinent changes in hematopoetic tissue. Sharply increased blood glucose and renal glucose excretion values were present in rats beginning with 18 months and were indicative of the development of non-insulin-dependent diabetes mellitus (NIDDM). The insulin concentrations in peripheral blood were not appreciably affected, although there was a trend to higher values in males at all evaluation times and in females only at 3 months. Pathological evaluation did not show any compound related non-neoplastic lesions. The incidences of islet cell adenomas in the pancreas of male rats were significantly increased and the cortical adenomas in the adrenals of females were decreased. In addition, the mammary gland adenomas (in females) and the Leydig cell tumors of the testes were decreased. In hamsters, the incidence of adrenocortical adenomas were increased in the females. No other pertinent neoplastic changes were observed. In conclusion, the increases and decreases in benign neoplasms of hormone-sensitive tissues, appear to be the result of nutritionally/metabolism-induced modulation of the homeostasis in these 4 tissues in both species, and not the result of chronic glucose administration.

摘要

在最初16周内浓度逐渐增加后,从第17周直至第112周的研究期间,以30%的比例将D - 葡萄糖添加到饮食中,喂食50只雄性和50只雌性的斯普拉格 - 道利大鼠。另外10只雄性和10只雌性动物接受14个月的处理,然后处死用于中期检查。60只雄性和60只雌性叙利亚金黄地鼠以20%葡萄糖溶液的形式饮用自来水,为期80周。在每种情况下,由数量相等的未处理动物组成的组作为对照。处理未影响总体行为和死亡率。用葡萄糖处理的大鼠和地鼠体重显著增加,雄性大鼠最高增加16%,雌性大鼠最高增加26%,雄性和雌性地鼠最高增加15%。在大鼠中,体重增加在第14周时明显,在地鼠中在第10周时明显。给予葡萄糖的大鼠采食量略有增加,饮水量减少。然而,这两个参数在地鼠中均未受影响。血液学和组织病理学检查显示造血组织无相关变化。从18个月开始,大鼠的血糖和肾葡萄糖排泄值急剧增加,表明非胰岛素依赖型糖尿病(NIDDM)的发展。外周血中的胰岛素浓度未受到明显影响,尽管在所有评估时间点雄性有升高趋势,雌性仅在3个月时有升高趋势。病理评估未显示任何与化合物相关的非肿瘤性病变。雄性大鼠胰腺中胰岛细胞腺瘤的发生率显著增加,雌性大鼠肾上腺皮质腺瘤的发生率降低。此外,雌性的乳腺腺瘤和雄性睾丸的间质细胞瘤减少。在地鼠中,雌性肾上腺皮质腺瘤的发生率增加。未观察到其他相关的肿瘤性变化。总之,激素敏感组织良性肿瘤的增加和减少,似乎是营养/代谢诱导这两个物种这4种组织内稳态调节的结果,而非长期给予葡萄糖的结果。

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