Hepatic oxidative damage and Nrf2 pathway protein changes in rats following long-term manganese exposure
Hepatic oxidative damage and Nrf2 pathway protein changes in rats following long-term manganese exposure
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DOI：
10.1177/0748233721993311
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发表时间：
2021-05
影响因子：
1.9
通讯作者：
Xia Wang;Xubo Shen;Lei Chen;Qin Yu;Shimin Xiong;K. Tian;Yan Xie;Rong Zeng;Yuanzhong Zhou
中科院分区：
文献类型：
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作者：
Xia Wang;Xubo Shen;Lei Chen;Qin Yu;Shimin Xiong;K. Tian;Yan Xie;Rong Zeng;Yuanzhong Zhou
本研究探讨了长期锰暴露对大鼠肝脏氧化损伤的影响及其机制。将48只SPF级雄性大鼠随机分为低剂量组（10 mg/kg，n = 16）、高剂量组（50 mg/kg，n = 16）和对照组（无菌蒸馏水，n = 16）。12个月后处死大鼠，测定肝脏Mn水平和组织病理学变化。还测定了血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平以及肝脏丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-PX）、核因子E2相关因子-2（Nrf 2）、血红素加氧酶-1（HO-1）和NAD（P）H奎宁氧化还原酶-1（NQO 1）水平。高剂量锰组的锰浓度和相对肝脏重量显著高于对照组和低剂量锰暴露组。低剂量锰暴露导致肝窦和完整的细胞核轻度扩张，而高剂量暴露导致肝细胞的病理改变。高剂量锰处理显著提高AST、ALT和MDA活性，降低GSH-PX活性。此外，肝脏Nrf 2，HO-1和NQO 1蛋白表达显着降低锰暴露。在本研究条件下，长期低剂量锰暴露导致肝脏结构轻微病变，而高剂量锰暴露则影响肝脏结构和功能，这可能与抑制Nrf 2表达、抑制其潜在抗氧化基因转录、下调相应蛋白有关。因此，大鼠肝脏的抗氧化能力减弱。
This study investigated hepatic oxidative damage in rats following long-term manganese (Mn) exposure and clarified the underlying mechanisms. Forty-eight rats (SPF, male) were randomly assigned to receive low (10 mg/kg, n = 16) or high doses of Mn (50 mg/kg, n = 16) or sterilized distilled water (control group, n = 16). Rats were euthanized after 12 months, and liver Mn levels and histopathological changes were determined. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver malondialdehyde (MDA), glutathione peroxidase (GSH-PX), nuclear factor E2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinine oxidoreductase-1 (NQO1) levels were also determined. The Mn concentration and relative liver weights were significantly higher in the high-dose Mn group than in the control and low-dose Mn exposure groups. Low-dose Mn exposure resulted in mild expansion of hepatic sinuses and intact nuclei, whereas high-dose exposure led to pathological alterations in hepatocytes. High-dose Mn treatment significantly increased AST, ALT, and MDA activities and decreased GSH-PX activity. Additionally, liver Nrf2, HO-1, and NQO1 protein expression were markedly reduced by Mn exposure. Under the study conditions, long-term low-dose Mn exposure resulted in slight pathological changes in liver structure, but high-dose Mn exposure affected both liver structure and function, which might be related to the inhibition of Nrf2 expression, suppression of the transcription of its underlying antioxidant genes, and down regulation of the corresponding proteins. Consequently, the antioxidant capacity in the rat liver was weakened.