Maneb disturbs expression of superoxide dismutase and glutathione peroxidase, increases reactive oxygen species production, and induces genotoxicity in liver of adult mice
Maneb disturbs expression of superoxide dismutase and glutathione peroxidase, increases reactive oxygen species production, and induces genotoxicity in liver of adult mice
复制标题
DOI：
10.1007/s11356-015-4434-6
复制
发表时间：
2015-08-01
影响因子：
5.8
通讯作者：
Zeghal, Najiba
中科院分区：
文献类型：
--
作者：
Ben Amara, Ibtissem;Ben Saad, Hajer;Zeghal, Najiba
Maneb(MB)是一种在包括突尼斯在内的世界各地的农业中广泛使用的杀菌剂，它保护许多蔬菜、水果和大田作物免受各种真菌疾病的侵袭。然而，缺乏关于甲基溴暴露于非目标生物，特别是哺乳动物的风险的信息。本研究的目的是研究小鼠暴露于MB后肝损伤的形态、生化和分子方面的变化。给成年小鼠注射相当于致死量的1/8(D1组)、1/6(D2组)、1/4(D3组)和1/2(D4组)的4种剂量的亚甲基蓝(DL50=1500 mg/kg体重)。氧化应激参数也被肝脏中的分子和组织学终点客观化。甘露醇可引起肝脏毒性，表现为丙二醛和蛋白质氧化标记物高级氧化蛋白产物(AOPP)水平显著升高。各处理组小鼠的过氧化氢酶、谷胱甘肽过氧化物酶、超氧化物歧化酶活性和谷胱甘肽含量均显著降低，而维生素C含量仅在D4组降低。我们还注意到超氧化物歧化酶和谷胱甘肽过氧化物酶的基因表达显著下降。Maneb引起核酸降解，证明了其遗传毒性。然而，所有治疗组的血浆生化标志物显示总蛋白下降，天冬氨酸、丙氨酸氨基转移酶和胆红素水平上升。此外，血浆胆固醇、甘油三酯和低密度脂蛋白胆固醇水平显著升高，而高密度脂蛋白胆固醇水平显著下降。这些生化改变与显著的组织学改变相关。我们的数据首次表明，成年小鼠腹腔注射非常高的非环境相关MB浓度会导致氧化应激，导致肝脏毒性和防御系统受损，证实了这种杀菌剂的促氧化和遗传毒性作用。
Maneb (MB), a fungicide largely used in agriculture throughout the world including Tunisia, protects many vegetables, fruits and field crops against a wide spectrum of fungal diseases. However there is a lack of informations regarding the risks arising from MB exposure on non target organisms, especially mammals. The aim of this study was to investigate the morphological, biochemical and molecular aspects of liver injury after exposure of mice to MB. Four doses of MB corresponding to 1/8 (group D1), 1/6 (group D2), 1/4 (group D3), and 1/2 (group D4) of lethal dose (DL50=1500 mg/kg body weight) were administered to adult mice. Oxidative stress parameters were also objectified by molecular and histological endpoints in the liver. Maneb caused hepatotoxicity as characterized by the significant increase in the levels of malondialdehyde and protein oxidation marker, advanced oxidation protein products (AOPP). The activities of catalase, glutathione peroxidase, superoxide dismutase and the levels of glutathione decreased significantly in all treated mice, while vitamin C levels decreased only in group D4. We also noted a significant decrease in gene expression of superoxide dismutase and glutathione peroxidase enzymes. Maneb caused nucleic acids degradation testifying its genotoxicity. Yet, biochemical markers in plasma showed a decrease in total protein and an increase in aspartate, alanine amino transferases and bilirubin levels in all treatment groups. Moreover, plasma levels of cholesterol, triglycerides and low density lipoprotein-cholesterol significantly increased, while those of high density lipoprotein-cholesterol decreased. These biochemical alterations were correlated with significantly histological changes. Our data showed, for the first time, that intraperitoneal injection of very high non environmentally relevant MB concentrations to adult mice resulted in oxidative stress leading to hepatotoxicity and the impairment of defense systems, confirming the pro-oxidant and genotoxic effects of this fungicide.