Inflammation, oxidative stress and apoptosis cascade implications in bisphenol A-induced liver fibrosis in male rats
Inflammation, oxidative stress and apoptosis cascade implications in bisphenol A-induced liver fibrosis in male rats
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DOI：
10.1111/iep.12207
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发表时间：
2016-10-01
影响因子：
3
通讯作者：
Hasan, Rehab Abdallah
中科院分区：
文献类型：
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作者：
Elswefy, Sahar El-Sayed;Abdallah, Fatma Rizk;Hasan, Rehab Abdallah
双酚A（BPA）是塑料生产中的关键单体。它已被证明是肝毒性。炎症和氧化应激与肝纤维化密切相关，肝纤维化是肝衰竭的主要促成因素。因此，本研究的目的是评估长期暴露于BPA对雄性大鼠肝纤维化发展的影响，并确定肝脏细胞因子网络、氧化应激和细胞凋亡之间的相互作用。为此目的，将30只雄性Wistar白化病大鼠分成如下三个相等的组：第一组不给予治疗（正常对照组）;第二组通过口服管饲法给予玉米油，每天一次，持续8周（媒介物对照组）;第三组接受BPA（50 mg/kg体重/天，p.o.）8周。BPA给药诱导肝纤维化，反映在血清肝酶活性增加，肝羟脯氨酸含量和组织病理学变化，特别是增加了门静脉周围的胶原纤维沉积。此外，还有炎症（反映在白细胞介素-1 β“IL-1 β”升高、白细胞介素-10“IL-100血清水平降低和IL-1 β/IL-10比值升高）、氧化应激（如丙二醛（MDA）水平的增加所反映的，还原型谷胱甘肽（GSH）含量的减少和过氧化氢酶（CAT）活性的抑制）和细胞凋亡[如半胱天冬酶-3水平和B细胞淋巴瘤2（BCL 2）免疫阳性肝细胞数量减少]。有趣的是，BPA对细胞外基质转换基因有上调作用[如基质金属蛋白酶-9（MMP-9）所反映]，对其抑制剂基因有下调作用[如基质金属蛋白酶组织抑制剂-2（TIMP-2）所反映]。因此，BPA诱导肝纤维化的机制似乎与炎症反应的刺激、氧化应激、细胞凋亡途径和细胞外基质周转的活化沿着有关。
Bisphenol A (BPA) is a key monomer in the production of plastics. It has been shown to be hepatotoxic. Inflammation and oxidative stress are closely linked with liver fibrosis, the major contributing factor to hepatic failure. Therefore, the aim of this study was to evaluate the impact of chronic exposure to BPA on the development of hepatic fibrosis in male rats and to determine the cross-talk between the hepatic cytokine network, oxidative stress and apoptosis. For this purpose, 30 male Wistar albino rats were divided into three equal groups as follows: the first group was given no treatment (normal control group); the second group was given corn oil once daily by oral gavage for 8 weeks (vehicle control group); and the third group received BPA (50 mg/kg body weight/day, p.o.) for 8 weeks. BPA administration induced liver fibrosis as reflected in an increase in serum hepatic enzymes activities, hepatic hydroxyproline content and histopathological changes particularly increased collagen fibre deposition around the portal tract. In addition, there was inflammation (as reflected in increase in interleukin-1beta 'IL-1 beta', decrease in interleukin-10 'IL-100 serum levels and increase in IL-1 beta/IL-10 ratio), oxidative stress (as reflected in increase in malondialdehyde (MDA) level, reduction in reduced glutathione (GSH) content and inhibition of catalase (CAT) activity) and apoptosis [as reflected in an increase in caspase-3 level and a decrease in numbers of B-cell lymphoma 2 (BCL2)-immunopositive hepatocytes]. Interestingly, BPA had an upregulating effect on an extracellular matrix turnover gene [as reflected in matrix metalloproteinase-9 (MMP-9)] and a downregulating effect on its inhibitor gene [as reflected in tissue inhibitor of matrix metalloproteinase-2 (TIMP-2)] expression. Thus, the mechanism by which BPA induced liver fibrosis seems to be related to stimulation of the inflammatory response, along with oxidative stress, the apoptotic pathway and activation of extracellular matrix turnover.