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长期接触有机磷农药后小鼠的肝损伤及氨基酸代谢紊乱

Hepatic injury and disturbed amino acid metabolism in mice following prolonged exposure to organophosphorus pesticides.

作者信息

Gomes J, Dawodu A H, Lloyd O, Revitt D M, Anilal S V

机构信息

Department of Community Medicine, Faculty of Medicine & Health Sciences, United Arab Emirates.

出版信息

Hum Exp Toxicol. 1999 Jan;18(1):33-7. doi: 10.1177/096032719901800105.

Abstract

Chronic occupational exposure to organophosphorus and carbamate-type pesticides significantly inhibits acetylcholinesterase activity and causes morbidity. This study on mice was designed to evaluate their amino profile and to identify signs of hepatic dysfunction following their chronic exposure to mixtures of organophosphorus pesticides. Laboratory mice were exposed to a formulated mixture of the six organophosphorus pesticides (Dimethoate, Chlorpyrifos, Profenofos, Pirimiphos methyl, Triazophos and Dimethoate) most commonly used in agriculture in this region of the Middle East. Doses (10% of LD50 of the mixture) were given once a week by gavage in corn oil for 7 weeks; the control group was given only corn oil. At the end of the exposure period, mice were culled and blood samples were collected to determine erythrocyte acetylcholinesterase activity, biochemical markers of liver function and concentrations of serum amino acids. Erythrocyte acetylcholinesterase activity and total serum proteins decreased significantly in the exposed group. Serum concentrations of alanine aminotransferase and aspartate aminotransferase, alanine, glutamic acid, glycine, isoleucine, leucine, methionine, ornithine, proline, serine, threonine and valine were significantly increased in the exposed mice, while serum levels of cystine were decreased significantly. There were also non-significant increases in serum alkaline phosphatase, gama-glutamyl transpeptidase and some of the other amino acids. Chronic exposure to mixtures of organophosphorus pesticides is associated with decreased acetylcholinesterase activity, hepatic dysfunction and disturbance of amino acids profile. Biochemical indices of hepatocellular injury and disturbed amino acid metabolism may be of value as markers of chronic exposure to such pesticides.

摘要

长期职业性接触有机磷和氨基甲酸酯类农药会显著抑制乙酰胆碱酯酶活性并导致发病。本研究以小鼠为对象,旨在评估其氨基酸谱,并确定它们长期接触有机磷农药混合物后的肝功能障碍迹象。将实验室小鼠暴露于中东该地区农业中最常用的六种有机磷农药(乐果、毒死蜱、丙溴磷、甲基嘧啶磷、三唑磷和乐果)的配方混合物中。剂量为混合物半数致死量的10%,每周一次通过灌胃给予玉米油,持续7周;对照组仅给予玉米油。在暴露期结束时,对小鼠实施安乐死并采集血样,以测定红细胞乙酰胆碱酯酶活性、肝功能生化指标和血清氨基酸浓度。暴露组的红细胞乙酰胆碱酯酶活性和血清总蛋白显著降低。暴露小鼠的血清丙氨酸转氨酶、天冬氨酸转氨酶、丙氨酸、谷氨酸、甘氨酸、异亮氨酸、亮氨酸、蛋氨酸、鸟氨酸、脯氨酸、丝氨酸、苏氨酸和缬氨酸浓度显著升高,而血清胱氨酸水平显著降低。血清碱性磷酸酶、γ-谷氨酰转肽酶和其他一些氨基酸也有不显著的升高。长期接触有机磷农药混合物与乙酰胆碱酯酶活性降低、肝功能障碍和氨基酸谱紊乱有关。肝细胞损伤的生化指标和氨基酸代谢紊乱可能作为长期接触此类农药的标志物具有重要价值。

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