Naraharisetti Suresh Babu, Aggarwal Manoj, Sarkar S N, Malik J K
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India.
Arch Toxicol. 2008 Aug;82(8):543-51. doi: 10.1007/s00204-008-0318-6. Epub 2008 Jun 5.
Arsenic is a known global groundwater contaminant, while malathion is one of the most widely used pesticides in agriculture and public health practices in the world. Here, we investigated whether repeated exposure to arsenic at the groundwater contamination levels and to malathion at sublethal levels exerts adverse effects on the hepatic drug-metabolizing system in rats, and whether concurrent exposure is more hazardous than the single agent. Male Wistar rats were exposed daily to 4 or 40 ppm of arsenic via drinking water, 50 or 500 ppm of malathion-mixed feed and in a similar fashion co-exposed to 4 ppm of arsenic and 50 ppm of malathion or 40 ppm of arsenic and 500 ppm of malathion for 28 days. At term, toxicity was assessed by evaluating changes in body weight, liver weight, levels of cytochrome P(450) (CYP), cytochrome b (5) and microsomal and cytosolic proteins, and activities of aminopyrine-N-demethylase (ANDM), aniline-P-hydroxylase (APH), glutathione-S-transferase (GST) and uridine diphosphate glucuronosyltransferase (UGT) in liver. Arsenic and malathion alone did not alter body weight and liver weight, but these were significantly decreased in both the co-exposed groups. These treatments decreased the activities of ANDM and APH and the levels of liver microsomal and cytosolic proteins, increased GST activity and had no effect on UGT activity. The effects of exposure to low-dose and high-dose combinations on the activities of either phase I or phase II drug-metabolizing enzymes and protein content were mostly similar to that produced by the respective low and high dose of either arsenic or malathion, except APH activity. The effect of arsenic (40 ppm) on APH activity was partially, but significantly, inhibited by malathion (500 ppm). Results indicate that the body or liver weights and the biochemical parameters were differentially affected in male rats following concurrent subacute exposure to arsenic and malathion, with the co-exposure appearing more hazardous to physical variables based on body or liver weights whilst producing biochemical changes comparable to those caused by the individual agents. From these findings, no specific toxicological interaction between arsenic and malathion can be conclusively generalized.
砷是一种全球范围内已知的地下水污染物，而马拉硫磷是世界农业和公共卫生实践中使用最广泛的杀虫剂之一。在此，我们研究了在地下水污染水平下反复接触砷以及在亚致死水平下接触马拉硫磷是否会对大鼠肝脏药物代谢系统产生不利影响，以及同时接触是否比单一药剂更具危害性。雄性Wistar大鼠每天通过饮用水接触4或40 ppm的砷，通过混合饲料接触50或500 ppm的马拉硫磷，并以类似方式同时接触4 ppm的砷和50 ppm的马拉硫磷或40 ppm的砷和500 ppm的马拉硫磷，持续28天。在实验末期，通过评估体重、肝脏重量、细胞色素P(450)（CYP）、细胞色素b(5)以及微粒体和胞质蛋白水平的变化，以及肝脏中氨基比林-N-脱甲基酶（ANDM）、苯胺-P-羟化酶（APH）、谷胱甘肽-S-转移酶（GST）和尿苷二磷酸葡萄糖醛酸转移酶（UGT）的活性来评估毒性。单独的砷和马拉硫磷不会改变体重和肝脏重量，但在两个同时接触组中这些指标均显著下降。这些处理降低了ANDM和APH的活性以及肝脏微粒体和胞质蛋白的水平，增加了GST活性，并且对UGT活性没有影响。低剂量和高剂量组合暴露对I相或II相药物代谢酶活性和蛋白质含量的影响大多与各自低剂量和高剂量的砷或马拉硫磷产生的影响相似，但APH活性除外。砷（40 ppm）对APH活性的影响被马拉硫磷（500 ppm）部分但显著地抑制。结果表明，雄性大鼠在同时亚急性接触砷和马拉硫磷后，体重或肝脏重量以及生化参数受到不同程度的影响，基于体重或肝脏重量，同时接触对身体变量似乎更具危害性，而产生的生化变化与单一药剂引起的变化相当。从这些发现中，无法确凿地归纳出砷和马拉硫磷之间存在特定的毒理学相互作用。
