Differential Hepatic Gene Expression and Antioxidant Activity in Male and Female Rats Induced by Subchronic Aflatoxicosis B1

G. Omran, N. el-Maali, M. Ismail, Nashwa A Ahmed, M. Mostafa, N. Nasser
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引用次数: 3

Abstract

Aflatoxin B1 (AFB1) is the most toxic mycotoxin that was proven to be deleterious to human and several animal species. Current work aimed at evaluating the sex-based differential hepatic genotoxic effect and the antioxidant activity as implications of subchronic aflatoxicosis B1. Albino rats were used that comprised two equal AFB1treated groups with AFB1 contaminated olive oil (50µg/kg) and a control group for each gender that received the vehicle only. Parts of animals’ livers were homogenized for gene expression assessment using quantitative RT-PCR and antioxidant activity analyses. Caspase-3 immunohistopathological examination was concomitantly undertaken. Results showed that AFB1 induced significant overexpression in cell cycle proliferation (ODC1), apoptosis (Aen), and antioxidant heme oxygenase (Hmox) genes in males alongside Bax (Bcl2- associated protein) under-expression. Meanwhile, female rats showed significant overexpression for (Hmox) and under-expression of Bax and Tnf (Tumor necrosis factor). Concomitant total hepatic antioxidant activity of liver homogenates showed a reduction in males, contrasting females. Degenerate vacuolated hepatocytes, polymorphic nuclei, cellular infiltration with concomitant Caspase-3 positive cells were profound findings in male rats. Hence, AFB1 is deferentially genotoxic at the given dose especially to male rats towards carcinogenicity, oxidative stress and apoptosis compared to a brief but compensated oxidative stress in females.
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亚慢性黄曲霉毒素B1诱导的雌雄大鼠肝脏基因表达差异及抗氧化活性
黄曲霉毒素B1 (AFB1)是毒性最强的真菌毒素,已被证明对人类和几种动物有害。目前的研究旨在评估亚慢性黄曲霉毒素B1的性别差异肝基因毒性效应和抗氧化活性。白化病大鼠分为两个等量的AFB1处理组,分别给予AFB1污染的橄榄油(50µg/kg)和每个性别的对照组,只接受载具。部分动物肝脏均质化,使用定量RT-PCR和抗氧化活性分析进行基因表达评估。同时进行Caspase-3免疫组织病理学检查。结果显示,AFB1诱导雄性细胞周期增殖(ODC1)、细胞凋亡(Aen)和抗氧化血红素加氧酶(Hmox)基因过表达,同时Bcl2相关蛋白Bax基因过表达。雌性大鼠(Hmox)高表达,Bax、Tnf(肿瘤坏死因子)低表达。同时,肝脏匀浆的总抗氧化活性在男性中降低,而在女性中则相反。雄性大鼠的肝细胞变性、细胞核多形性、细胞浸润伴Caspase-3阳性细胞。因此,在给定剂量下,AFB1对雄性大鼠具有致癌、氧化应激和细胞凋亡的遗传毒性,而对雌性大鼠具有短暂但可补偿的氧化应激。
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