Bashir Somia, Sharma Yukti, Irshad M, Gupta S Dutta, Dogra T D
Department of Forensic Medicine & Toxicology, All India Institute of Medical Sciences (AIIMS), New Delhi-29, India.
Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):38-43. doi: 10.1111/j.1742-7843.2006.pto_170.x.
Arsenic is a well established human carcinogen and is ubiquitous in the environment. The present study demonstrates the effect of acute arsenic administration at three different doses in liver and brain of Wistar rats. Sodium arsenite was administered orally at doses of 6.3 mg/kg, 10.5 mg/kg and 12.6 mg/kg of body weight on the basis of a lethal dose 50% (LD50) for 24 hr. After administration of arsenites, liver and brain were analyzed for various parameters of oxidative stress, histopathological changes and caspase-3 activity. Glutathione levels were decreased significantly in the liver at all doses. In liver the following biochemical changes were observed, a significant lipid peroxidation and cytochrome-P450 induction along with significant decrease in catalase and superoxide dismutase was observed at 10.5 mg/kg and 12.6 mg/kg. The activity of glutathione peroxidase was increased significantly at all doses. In brain, no significant change was observed at 6.3 mg/kg. However, a significant increase in lipid peroxidation and glutathione peroxidase activity along with significant decrease in the activity of glutathione, catalase and superoxide dismutase was observed at 10.5 mg/kg and 12.6 mg/kg. The activity of glutathione-S-transferase was decreased significantly in both liver and brain at 10.5 and 12.6 mg/kg. No significant alteration in the activity of glucose-6-phosphate dehydrogenase and glutathione reductase was observed in either liver or brain at any dose. Dose-dependent histopathological changes, observed in both liver and brain are also described. A significant increase in caspase-3 activity was observed at all doses in liver and at 10.5 and 12.6 mg/kg in brain. Sodium arsenite caused DNA cleavage into fragments and manifested as "DNA laddering", a hallmark of apoptosis.
砷是一种已被充分证实的人类致癌物，在环境中广泛存在。本研究展示了以三种不同剂量急性给予砷对Wistar大鼠肝脏和大脑的影响。根据半数致死剂量（LD50），以6.3毫克/千克、10.5毫克/千克和12.6毫克/千克体重的剂量口服亚砷酸钠24小时。给予亚砷酸盐后，对肝脏和大脑进行氧化应激、组织病理学变化和半胱天冬酶-3活性等各项参数的分析。所有剂量下肝脏中的谷胱甘肽水平均显著降低。在肝脏中观察到以下生化变化：在10.5毫克/千克和12.6毫克/千克剂量时，脂质过氧化和细胞色素P450诱导显著增加，同时过氧化氢酶和超氧化物歧化酶显著减少。所有剂量下谷胱甘肽过氧化物酶的活性均显著增加。在大脑中，6.3毫克/千克剂量时未观察到显著变化。然而，在10.5毫克/千克和12.6毫克/千克剂量时，脂质过氧化和谷胱甘肽过氧化物酶活性显著增加，同时谷胱甘肽、过氧化氢酶和超氧化物歧化酶的活性显著降低。在10.5和12.6毫克/千克剂量时，肝脏和大脑中的谷胱甘肽-S-转移酶活性均显著降低。在任何剂量下，肝脏或大脑中葡萄糖-6-磷酸脱氢酶和谷胱甘肽还原酶的活性均未观察到显著改变。还描述了在肝脏和大脑中观察到的剂量依赖性组织病理学变化。在肝脏的所有剂量以及大脑的10.5和12.6毫克/千克剂量下，半胱天冬酶-3活性均显著增加。亚砷酸钠导致DNA断裂成片段，并表现为“DNA梯状条带”，这是细胞凋亡的标志。
