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全氯乙烯诱导的小鼠葡萄糖代谢改变以及2-脱氧-D-葡萄糖和维生素E对其的预防作用

Perchloroethylene-induced alterations in glucose metabolism and their prevention by 2-deoxy-D-glucose and vitamin E in mice.

作者信息

Ebrahim A S, Babakrishnan K, Sakthisekaran D

机构信息

Department of Medical Biochemistry, University of Madras, India.

出版信息

J Appl Toxicol. 1996 Jul-Aug;16(4):339-48. doi: 10.1002/(SICI)1099-1263(199607)16:4<339::AID-JAT352>3.0.CO;2-3.

Abstract

The effect of 2-deoxy-D-glucose (2DG) and vitamin E on the alterations in glucose metabolism induced by perchloroethylene (PER) was studied in mice. Oral administration of PER (3 g kg-1 body wt. day-1) in sesame oil for 15 days caused a significant increase in liver weight, degeneration/necrosis of hepatocytes and increase in kidney weight, glomerular nephrosis and degeneration. These changes occurred concurrently with a significant decrease in blood glucose level, elevated activities of hexokinase, aldolase and phosphoglucoisomerase and decreased activity of gluconeogenic enzymes (glucose-6-phosphatase and fructose-1,6-diphosphatase), indicating the sensitivity of liver and kidney as target tissues in PER toxicity. Evidence is presented that both 2DG (500 mg kg-1 body wt. day-1 i.p.) and vitamin E (400 mg kg-1 body wt. day-1 by oral gavage) during concomitant administration prevented most of the above PER-induced biochemical and pathological alterations. These results suggest that early metabolic and pathological perturbations following exposure of PER in mice can provide the basis for its documented potential for chronic effects like cytotoxicity and may be involved in modulation of carcinogenicity.

摘要

在小鼠中研究了2-脱氧-D-葡萄糖(2DG)和维生素E对全氯乙烯(PER)诱导的葡萄糖代谢改变的影响。以芝麻油为溶剂,按3 g/kg体重/天的剂量给小鼠口服PER,持续15天,导致肝脏重量显著增加、肝细胞变性/坏死,以及肾脏重量增加、肾小球性肾病和变性。这些变化同时伴随着血糖水平显著降低、己糖激酶、醛缩酶和磷酸葡萄糖异构酶活性升高,以及糖异生酶(葡萄糖-6-磷酸酶和果糖-1,6-二磷酸酶)活性降低,表明肝脏和肾脏作为PER毒性的靶组织具有敏感性。有证据表明,在同时给药期间,2DG(500 mg/kg体重/天,腹腔注射)和维生素E(400 mg/kg体重/天,经口灌胃)可预防上述大多数由PER诱导的生化和病理改变。这些结果表明,小鼠接触PER后早期的代谢和病理扰动可为其已记录的细胞毒性等慢性影响的潜在可能性提供依据,并且可能参与致癌性的调节。

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