Ghorbel Imen, Maktouf Sameh, Fendri Nesrine, Jamoussi Kamel, Ellouze Chaabouni Semia, Boudawara Tahia, Zeghal Najiba
Animal Physiology Laboratory, Sfax Faculty of Sciences, University of Sfax, 3000 Sfax, BP 1171, Tunisia.
Enzymes and Bioconversions Laboratory, National Engineering School, University of Sfax, BP 1173, 3038, Sfax, Tunisia.
Environ Toxicol. 2016 Sep;31(9):1044-58. doi: 10.1002/tox.22114. Epub 2015 Apr 9.
The individual toxic effects of aluminum and acrylamide are known but there is no data on their combined effects. The present study investigates the toxic effects after combined exposure to these toxicants on: (i) oxidative stress during combined chronic exposure to aluminum and acrylamide on kidney function (ii) correlation of oxidative stress with metallothionein (MT) and inflammatory cytokines expression, DNA damage, and histopathological changes. Rats were exposed to aluminum (50 mg/kg body weight) in drinking water and acrylamide (20 mg/kg body weight) by gavage either individually or in combination for 3 weeks. Exposure rats to aluminum chloride or acrylamide alone and in combination induced nephrotoxicity, as evidenced by a decrease in the 24-h urine volume and uric acid levels in plasma and an increase of plasma creatinine, urea, and blood urea nitrogen levels. Nephrotoxicity was objectified by a significant increase in malondialdehyde level, advanced oxidation protein, and protein carbonyl contents, whereas reduced glutathione, nonprotein thiol, vitamin C levels, catalase, and glutathione peroxidase activities showed a significant decline. Superoxide dismutase activity and its gene expression were increased. Aluminum and acrylamide co-exposure exhibited synergism in various biochemical variables and also in DNA damage. Kidney total MT levels and genes expression of MT1, MT2, and proinflammatory cytokines were increased. All these changes were supported by histopathological observations. Co-exposure to aluminum and acrylamide exhibited synergism and more pronounced toxic effects compared with their individual effects based on various biochemical variables, genotoxic, and histopathological changes. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1044-1058, 2016.
铝和丙烯酰胺的个体毒性作用已为人所知，但尚无关于它们联合作用的数据。本研究调查了联合暴露于这些毒物后对以下方面的毒性作用：（i）铝和丙烯酰胺联合慢性暴露对肾功能的氧化应激；（ii）氧化应激与金属硫蛋白（MT）、炎性细胞因子表达、DNA损伤及组织病理学变化的相关性。将大鼠分别单独或联合经口灌胃给予丙烯酰胺（20 mg/kg体重），并通过饮水给予铝（50 mg/kg体重），持续3周。单独或联合暴露于氯化铝或丙烯酰胺均诱导了肾毒性，这可通过24小时尿量减少、血浆尿酸水平降低以及血浆肌酐、尿素和血尿素氮水平升高得以证明。丙二醛水平、晚期氧化蛋白和蛋白羰基含量显著增加，而还原型谷胱甘肽、非蛋白硫醇、维生素C水平、过氧化氢酶和谷胱甘肽过氧化物酶活性显著下降，从而证实了肾毒性。超氧化物歧化酶活性及其基因表达增加。铝和丙烯酰胺联合暴露在各种生化变量以及DNA损伤方面均表现出协同作用。肾脏总MT水平以及MT1、MT2和促炎细胞因子的基因表达增加。所有这些变化均得到组织病理学观察结果的支持。基于各种生化变量、遗传毒性和组织病理学变化，铝和丙烯酰胺联合暴露相比其单独作用表现出协同作用且毒性作用更明显。© 2015威利期刊公司。《环境毒理学》31: 1044 - 1058, 2016。
