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单独使用百里醌或依布硒啉对大鼠砷诱导肝毒性的保护作用。

Protective efficacy of thymoquinone or ebselen separately against arsenic-induced hepatotoxicity in rat.

机构信息

Department of Internal Medicine, College of Medicine, Taif University, Taif, Saudi Arabia.

Biotechnology Department, College of Science, Taif University, Taif, Saudi Arabia.

出版信息

Environ Sci Pollut Res Int. 2021 Feb;28(5):6195-6206. doi: 10.1007/s11356-020-10955-1. Epub 2020 Sep 29.

DOI:10.1007/s11356-020-10955-1
PMID:32989703
Abstract

Arsenic (As) exposure is associated with adverse health outcomes to the living organisms. In the present study, the hepato-protective ability of thymoquinone (TQ), the active principle of Nigella sativa seed, or ebselen (Eb), an organoselenium compound, against As intoxication in female rats was investigated. For this purpose, animals were allocated randomly into control, As (20 mg/kg), TQ (10 mg/kg), Eb (5 mg/kg), As+TQ, and As+Eb groups that were orally administered for 28 consecutive days. Arsenic exposure resulted in hepatic oxidative damage which was evidenced by marked decreases in antioxidant parameters (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH)) concomitant with high malondialdehyde (MDA) level. Furthermore, As toxicity induced significant elevations in liver accumulation of As, serum hepatic indices (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (TB)), and apoptotic marker (B cell lymphoma 2(Bcl2), Bcl-2-associated X protein (Bax), and caspase 3) levels. Additionally, notable increments in hepatic fibrotic markers (epidermal growth factor (EFG) and transforming growth factor beta 1 (TGF-β1)) associated with high nitric oxide, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and myeloperoxidase (MPO) levels were noticed following As intoxication. Biochemical findings were well-supported by hepatic histopathological screening. The co-treatment of As-exposed rats with TQ or Eb considerably improved liver function and antioxidant status together with lessened hepatic As content, inflammation, apoptosis, and fibrosis. The overall outcomes demonstrated that TQ or Eb ameliorates As-induced liver injury through their favorable antioxidant, anti-inflammatory, anti-apoptotic, and fibrolytic properties.

摘要

砷(As)暴露会对生物体的健康产生不良影响。在本研究中,研究了黑种草种子的活性成分百里醌(TQ)或有机硒化合物依布硒啉(Eb)对雌性大鼠砷中毒的肝保护作用。为此,将动物随机分为对照组、As(20mg/kg)组、TQ(10mg/kg)组、Eb(5mg/kg)组、As+TQ 组和 As+Eb 组,连续 28 天口服给药。砷暴露导致肝氧化损伤,表现为抗氧化参数(超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽还原酶(GR)和谷胱甘肽(GSH))明显下降,同时丙二醛(MDA)水平升高。此外,砷毒性引起肝砷蓄积、血清肝指标(天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)和总胆红素(TB))和凋亡标志物(B 细胞淋巴瘤 2(Bcl2)、Bcl-2 相关 X 蛋白(Bax)和半胱天冬酶 3(caspase 3))水平显著升高。此外,砷中毒后还观察到肝纤维化标志物(表皮生长因子(EGF)和转化生长因子β1(TGF-β1))显著增加,同时伴有一氧化氮、白细胞介素 6(IL-6)、肿瘤坏死因子α(TNF-α)和髓过氧化物酶(MPO)水平升高。肝脏组织病理学筛选很好地支持了生化发现。As 暴露大鼠用 TQ 或 Eb 联合治疗可显著改善肝功能和抗氧化状态,同时减少肝砷含量、炎症、凋亡和纤维化。总的来说,这些结果表明 TQ 或 Eb 通过其有利的抗氧化、抗炎、抗凋亡和纤维溶解特性改善了 As 诱导的肝损伤。

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