Department of Toxicology & Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Centre, Tehran University of Medical Sciences, Tehran, Iran.
Toxicol Mech Methods. 2006;16(4):161-7. doi: 10.1080/15376520500191623.
Previous studies showed that malathion induces hyperglycemia mainly through influence on glucose metabolism in liver and skeletal muscles. The main objective of the present study was to determine what will happen on pancreatic key enzymes of insulin secretion, including glucokinase (GK) and glutamate dehydrogenase (GDH), if animals would be in acute or subchronic exposure to various doses of malathion, an organophosphorous insecticide in rats. In the subchronic study, malathion was administered orally at doses of 100 to 400 ppm for 4 weeks. In the acute experiment, animals received various doses of 3 to 75 mg/kg of malathion intraperitoneally. In each experiment, islets were isolated from the pancreas of rats by a standard collagenase digestion, separation by centrifugation, and hand-picking technique. The activities of the mitochondrial GDH and the nonmitochondrial GK enzymes were determined in islets homogenates spectrophotometrically. Blood sample was taken by cardiac puncture for glucose and insulin assays. In the acute experiment, malathion (3, 15, 75 mg/kg) increased blood glucose and insulin (15 and 75 mg/kg). In the subchronic experiment, malathion (100, 200, 400 ppm) increased blood glucose and insulin (200 and 400 ppm). All doses in both acute and subchronic experiments increased the mitochondrial GDH activity. Acute (15 and 75 ppm) and subchronic (200 and 400 ppm) increased the islets GK activity. It was concluded that pancreatic islet key enzymes are stimulated following acute and subchronic exposure to malathion though not enough to overcome to hyperglycemia. Activation of islets muscarinic receptors by malathion in favor of hyperinsulinemia, overproduction of glutamate/glutathione by GDH, and overproduction of glucose via increased glycogenolysis in counteracting with malathion-induced oxidative stress are possible mechanisms for observed effects. A new NOAEL acceptable daily intake must be established for malathion.
先前的研究表明，马拉硫磷主要通过影响肝脏和骨骼肌中的葡萄糖代谢来诱导高血糖。本研究的主要目的是确定在急性或亚慢性接触不同剂量马拉硫磷（一种有机磷杀虫剂）时，胰腺中胰岛素分泌的关键酶（包括葡糖激酶（GK）和谷氨酸脱氢酶（GDH））会发生什么情况。在亚慢性研究中，马拉硫磷经口给予 100 至 400ppm 剂量，持续 4 周。在急性实验中，动物腹膜内给予不同剂量的 3 至 75mg/kg 马拉硫磷。在每个实验中，通过标准胶原酶消化、离心分离和手动挑选技术从大鼠胰腺中分离胰岛。用分光光度法测定胰岛匀浆中线粒体 GDH 和非线粒体 GK 酶的活性。通过心脏穿刺采血测定血糖和胰岛素。在急性实验中，马拉硫磷（3、15、75mg/kg）增加了血糖和胰岛素（15 和 75mg/kg）。在亚慢性实验中，马拉硫磷（100、200、400ppm）增加了血糖和胰岛素（200 和 400ppm）。两个急性和亚慢性实验中的所有剂量均增加了线粒体 GDH 活性。急性（15 和 75ppm）和亚慢性（200 和 400ppm）增加了胰岛 GK 活性。结论是，胰腺胰岛关键酶在急性和亚慢性接触马拉硫磷后受到刺激，尽管不足以克服高血糖。马拉硫磷激活胰岛毒蕈碱受体有利于高胰岛素血症，GDH 过度产生谷氨酸/谷胱甘肽，以及通过增加糖原分解来产生葡萄糖，以抵消马拉硫磷诱导的氧化应激，这些可能是观察到的作用的机制。必须为马拉硫磷建立一个新的可接受的每日摄入量的无作用水平。
