Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243 122 (U.P.), India.
Environ Toxicol Pharmacol. 2009 Sep;28(2):213-8. doi: 10.1016/j.etap.2009.04.006. Epub 2009 Apr 15.
Groundwater contamination with arsenic is a major global health concern. The organophosphorus insecticide malathion has gained significance as an environmental pollutant due to its widespread use in agriculture, grain storage, ectoparasite control and public health management. The deleterious effects produced by arsenic or malathion alone are documented, but very little is known about the consequences of their coexposure. The aim of the current study was to examine the effects of repeated simultaneous exposure to arsenic and malathion on drug-biotransforming enzymes in the liver of broiler chickens. One-month-old broiler chickens were exposed daily to arsenic (50 ppm)-supplemented drinking water, malathion (500 ppm)-mixed diet or in a similar fashion coexposed to these agents for 28 days. At the term, changes in body weight, organ weights, and levels of hepatic cytochrome P450 (CYP), cytochrome b(5), microsomal and cytosolic proteins; aminopyrine N-demethylase (ANDM), aniline P-hydroxylase (APH), glutathione S-transferase (GST) and uridine diphosphate glucuronosyltransferase (UGT) were assessed. Arsenic, malathion or their coexposure decreased the body weight gain and liver weight. Brain weight (relative) was increased with arsenic or malathion, but not with the coexposure. Treatment with arsenic decreased the CYP and cytochrome b(5) contents by 39 and 36%, than with malathion by 54 and 22% and the coexposure by 45 and 28%, respectively. The ANDM activity was decreased with arsenic (44%), malathion (23%) and the coexposure (32%). Arsenic (23%) and the coexposure (37%), but not malathion (14%), reduced the APH activity. The activities of hepatic microsomal and cytosolic GST were increased with all the three treatments [Arsenic (microsomal: 88% cytosolic: 113%), malathion (microsomal: 137%, cytosolic: 94%) and coexposure (microsomal: 140%, cytosolic: 148%)]. These treatments did not significantly affect the hepatic UGT activity, but reduced the hepatic microsomal (arsenic: 28%, malathion: 34% and coexposure: 43%) and cytosolic (17-19%) protein contents. The effects of coexposure on the activities of various phase I and phase II drug-biotransforming enzymes were almost similar to that of arsenic or malathion. This study provides evidence that repeated coexposure to arsenic and malathion may influence the extent of drug metabolism in chickens.
地下水砷污染是一个全球性的主要健康问题。有机磷杀虫剂马拉硫磷由于在农业、粮食储存、寄生虫控制和公共卫生管理等领域的广泛应用，已成为一种重要的环境污染物。砷或马拉硫磷单独产生的有害影响已有文献记载，但它们共同暴露的后果知之甚少。本研究旨在探讨重复同时暴露于砷和马拉硫磷对肉鸡肝脏中药物代谢酶的影响。将 1 月龄肉鸡每日暴露于添加砷（50ppm）的饮用水、混有马拉硫磷（500ppm）的饮食或以类似方式同时暴露于这些物质 28 天。在试验结束时，评估了体重、器官重量、肝微粒体细胞色素 P450（CYP）、细胞色素 b(5)、微粒体和胞浆蛋白、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基转移酶（UGT）的水平变化。砷、马拉硫磷或其混合物暴露降低了体重增加和肝脏重量。与砷或马拉硫磷处理相比，脑组织重量（相对）增加，但与混合物暴露无差异。与马拉硫磷处理相比，砷处理使 CYP 和细胞色素 b(5)含量分别减少 39%和 36%，而混合物暴露使 CYP 和细胞色素 b(5)含量分别减少 45%和 28%。ANDM 活性分别降低了 44%、23%和 32%。与砷（23%）和混合物暴露（37%）相比，马拉硫磷（14%）降低了 APH 活性。肝微粒体和胞浆 GST 活性均因三种处理而增加[砷（微粒体：88%胞浆：113%）、马拉硫磷（微粒体：137%胞浆：94%）和混合物（微粒体：140%胞浆：148%）]。这些处理并未显著影响肝 UGT 活性，但降低了肝微粒体（砷：28%、马拉硫磷：34%和混合物：43%）和胞浆（17-19%）蛋白含量。混合物暴露对各种 I 相和 II 相药物代谢酶活性的影响与砷或马拉硫磷几乎相同。本研究提供的证据表明，重复同时暴露于砷和马拉硫磷可能影响鸡体内药物代谢的程度。
