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槲皮素对急性和亚慢性大鼠模型肝脏、肾脏和肺中锰诱导损伤的保护作用以及血液学参数

Protective role of quercetin against manganese-induced injury in the liver, kidney, and lung; and hematological parameters in acute and subchronic rat models.

作者信息

Bahar Entaz, Lee Geum-Hwa, Bhattarai Kashi Raj, Lee Hwa-Young, Kim Hyun-Kyoung, Handigund Mallikarjun, Choi Min-Kyung, Han Sun-Young, Chae Han-Jung, Yoon Hyonok

机构信息

College of Pharmacy, Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju.

Department of Pharmacology, Medical School, Chonbuk National University.

出版信息

Drug Des Devel Ther. 2017 Sep 5;11:2605-2619. doi: 10.2147/DDDT.S143875. eCollection 2017.

Abstract

Manganese (Mn) is an important mineral element required in trace amounts for development of the human body, while over- or chronic-exposure can cause serious organ toxicity. The current study was designed to evaluate the protective role of quercetin (Qct) against Mn-induced toxicity in the liver, kidney, lung, and hematological parameters in acute and subchronic rat models. Male Sprague Dawley rats were divided into control, Mn (100 mg/kg for acute model and 15 mg/kg for subchronic model), and Mn + Qct (25 and 50 mg/kg) groups in both acute and subchronic models. Our result revealed that Mn + Qct groups effectively reduced Mn-induced ALT, AST, and creatinine levels. However, Mn + Qct groups had effectively reversed Mn-induced alteration of complete blood count, including red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, and white blood cells. Meanwhile, the Mn + Qct groups had significantly decreased neutrophil and eosinophil and increased lymphocyte levels relative to the Mn group. Additionally, Mn + Qct groups showed a beneficial effect against Mn-induced macrophages and neutrophils. Our result demonstrated that Mn + Qct groups exhibited protective effects on Mn-induced alteration of GRP78, CHOP, and caspase-3 activities. Furthermore, histopathological observation showed that Mn + Qct groups effectively counteracted Mn-induced morphological change in the liver, kidney, and lung. Moreover, immunohistochemically Mn + Qct groups had significantly attenuated Mn-induced 8-oxo-2'-deoxyguanosine immunoreactivity. Our study suggests that Qct could be a substantially promising organ-protective agent against toxic Mn effects and perhaps against other toxic metal chemicals or drugs.

摘要

锰(Mn)是人体发育所需的一种重要的微量矿物元素,而过量或长期接触会导致严重的器官毒性。本研究旨在评估槲皮素(Qct)在急性和亚慢性大鼠模型中对锰诱导的肝脏、肾脏、肺脏毒性以及血液学参数的保护作用。在急性和亚慢性模型中,将雄性Sprague Dawley大鼠分为对照组、锰组(急性模型为100 mg/kg,亚慢性模型为15 mg/kg)以及锰+槲皮素组(25和50 mg/kg)。我们的结果显示,锰+槲皮素组有效降低了锰诱导的谷丙转氨酶、谷草转氨酶和肌酐水平。然而,锰+槲皮素组有效逆转了锰诱导的全血细胞计数变化,包括红细胞、血红蛋白、血细胞比容、平均红细胞体积、平均红细胞血红蛋白、平均红细胞血红蛋白浓度、血小板和白细胞。同时,相对于锰组,锰+槲皮素组的中性粒细胞和嗜酸性粒细胞显著减少,淋巴细胞水平增加。此外,锰+槲皮素组对锰诱导的巨噬细胞和中性粒细胞显示出有益作用。我们的结果表明,锰+槲皮素组对锰诱导的葡萄糖调节蛋白78、C/EBP同源蛋白和半胱天冬酶-3活性变化具有保护作用。此外,组织病理学观察表明,锰+槲皮素组有效抵消了锰诱导的肝脏、肾脏和肺脏形态学变化。而且,免疫组织化学结果显示,锰+槲皮素组显著减弱了锰诱导的8-氧代-2'-脱氧鸟苷免疫反应性。我们的研究表明,槲皮素可能是一种非常有前景的器官保护剂,可对抗锰的毒性作用,或许还能对抗其他有毒金属化学物质或药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e167/5592961/11ce839f9b66/dddt-11-2605Fig1.jpg

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