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一项评估抗癌药物(环磷酰胺)对斑马鱼健康影响的研究:新兴污染物的生态毒性

A study to assess the health effects of an anticancer drug (cyclophosphamide) in zebrafish (): eco-toxicity of emerging contaminants.

作者信息

Hema Tamilselvan, Mohanthi Sundaram, Umamaheswari Sathisaran, Ramesh Mathan, Ren Zongming, Poopal Rama-Krishnan

机构信息

Unit of Toxicology, Department of Zoology, Bharathiar University, Coimbatore, 641 046, TamilNadu, India.

Institute of Environment and Ecology, Shandong Normal University, Jinan 250358, People's Republic of China.

出版信息

Environ Sci Process Impacts. 2023 Apr 26;25(4):870-884. doi: 10.1039/d2em00527a.

Abstract

Cyclophosphamide (CP) is widely used for treating various kinds of cancer. Because of its high intake, metabolism and excretion, these anticancer medications have been detected in the aquatic environment. There is very limited data on the toxicity and effects of CP on aquatic organisms. The present study aims to assess the toxic effect of CP on certain oxidative stress biomarkers (superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase-GPx, glutathione-GSH, glutathione S-transferases-GST and lipid peroxidation-LPO), protein, glucose, metabolising enzymes (aspartate aminotransferase-AST, alanine aminotransferase-ALT), and ion-regulatory markers (sodium ions-Na, potassium ions-K, and chloride ions-Cl), and histology in the gills and liver of at environmentally relevant concentrations (10, 100 and 1000 ng L). Exposure to CP for 42 days led to a significant decrease in SOD, CAT, GST, GPx and GSH levels in the gills and liver tissues of zebrafish. The level of lipid peroxidation in the gills and liver tissues of zebrafish was significantly increased compared to the control group. Chronic exposure significantly changes protein, glucose, AST, ALT, Na, K and Cl biomarkers. Fish exposed to different levels of CP showed necrosis, inflammation, degeneration and hemorrhage in the gills and hepatic tissues. The observed changes in the studied tissue biomarkers were proportional to both dose and time. In conclusion, CP at environmentally relevant concentrations causes oxidative stress, energy demand, homeostasis disturbances, and enzyme and histological alterations in the vital tissues of zebrafish. These alterations were similar to the toxic effects reported in mammalian models.

摘要

环磷酰胺(CP)被广泛用于治疗各类癌症。由于其摄入量、代谢率及排泄率都很高,这些抗癌药物已在水生环境中被检测到。关于CP对水生生物的毒性和影响的数据非常有限。本研究旨在评估CP在环境相关浓度(10、100和1000纳克/升)下对某些氧化应激生物标志物(超氧化物歧化酶-SOD、过氧化氢酶-CAT、谷胱甘肽过氧化物酶-GPx、谷胱甘肽-GSH、谷胱甘肽S-转移酶-GST和脂质过氧化-LPO)、蛋白质、葡萄糖、代谢酶(天冬氨酸转氨酶-AST、丙氨酸转氨酶-ALT)以及离子调节标志物(钠离子-Na、钾离子-K和氯离子-Cl)的毒性作用,以及对斑马鱼鳃和肝脏的组织学影响。暴露于CP 42天导致斑马鱼鳃和肝脏组织中的SOD、CAT、GST、GPx和GSH水平显著下降。与对照组相比,斑马鱼鳃和肝脏组织中的脂质过氧化水平显著升高。长期暴露显著改变了蛋白质、葡萄糖、AST、ALT、Na、K和Cl生物标志物。暴露于不同水平CP的鱼类在鳃和肝脏组织中出现坏死、炎症、变性和出血。在所研究的组织生物标志物中观察到的变化与剂量和时间都成正比。总之,环境相关浓度的CP会在斑马鱼的重要组织中引起氧化应激、能量需求、体内平衡紊乱以及酶和组织学改变。这些改变与在哺乳动物模型中报告的毒性作用相似。

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