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甜菜汁和 2,3-二巯基丁二酸通过改善肝脏氧化和炎症应激对铅中毒大鼠的协同保肝作用。

The synergistic hepatoprotective potential of Beta vulgaris juice and 2,3- dimercaptosuccinic acid in lead-intoxicated rats via improving the hepatic oxidative and inflammatory stress.

机构信息

Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, 21511, Egypt.

Department of Nucleic Acid Research, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), New Borg EL-Arab, Alexandria, 21934, Egypt.

出版信息

BMC Complement Med Ther. 2020 Sep 1;20(1):268. doi: 10.1186/s12906-020-03056-6.

Abstract

BACKGROUND

Lead (Pb) is observed in all areas of the environment, mainly derived from human operations such as mining, processing, and burning fossil fuels. Pb toxicity is one of the most prevalent causes of human hepatotoxicity. The available chelator drugs used now have many adverse effects and therefore the world is looking for natural and secure alternatives.

METHODS

Here, we evaluated the hepatoprotective role of the oral administration (1 g/kg b.w.) of the lyophilized Beta vulgaris juice (BVJ) against Pb-induced rat hepatotoxicity. We also examined the possible synergistic hepatoprotective impact of the combination between BVJ and 2,3- dimercaptosuccinic acid (DMSA, the currently approved drug for Pb-toxicity). The evaluation depends on the ability of BVJ, DMSA, or their combination (BVJ-DMSA) to reduce serum and hepatic Pb level and to avoid oxidative stress and inflammation caused by Pb. The level of lipid peroxidation, reduced glutathione (GSH), total antioxidant capacity, and the activity of the antioxidant enzymes were quantified. In addition, the level of interleukin (IL)-6, nitric oxide (NO), DNA fragmentation, and liver histology were studied.

RESULTS

The results showed that BVJ contained considerable amounts of betalains, vitamin C, and various types of phenolic compounds. Therefore, BVJ displayed a significant (p < 0.05) preventive influence on the elevation of Pb levels in blood and liver as well as the hepatic DNA fragmentation. In addition, it significantly (p < 0.05) improved most of the studied antioxidant and inflammatory markers in the Pb-intoxicated rats. However, the combined extract (BVJ-DMSA) revealed synergistic (combination index < 1) activities in most of the tested parameters. The histopathological results verified the biochemical findings of this research.

CONCLUSION

BVJ has a potent efficiency in the protection from Pb-induced hepatotoxicity through the reduction of its accumulation in blood and liver and the prevention of the oxidative stress and inflammation induced by Pb. Additionally, the treatment of hepatotoxicity with BVJ and DMSA in combination showed a synergistic effect and reduced the adverse effects induced by DMSA. Thus, BVJ can be a promising hepatoprotective extract against lead toxicity and its combination with DMSA potentiates this effect.

摘要

背景

铅(Pb)存在于环境的各个领域,主要来源于采矿、加工和燃烧化石燃料等人类活动。铅毒性是导致人类肝毒性的最常见原因之一。目前可用的螯合剂药物有许多不良反应,因此全世界都在寻找天然、安全的替代品。

方法

在这里,我们评估了口服(1g/kg 体重)冻干蕹菜汁(BVJ)对铅诱导的大鼠肝毒性的保护作用。我们还研究了 BVJ 与 2,3-二巯基丁二酸(DMSA,目前批准用于铅毒性的药物)联合使用可能产生的协同保肝作用。评估取决于 BVJ、DMSA 或它们的组合(BVJ-DMSA)降低血清和肝脏中 Pb 水平以及避免由 Pb 引起的氧化应激和炎症的能力。定量测定脂质过氧化、还原型谷胱甘肽(GSH)、总抗氧化能力和抗氧化酶的活性。此外,还研究了白细胞介素(IL)-6、一氧化氮(NO)、DNA 片段化和肝组织学的水平。

结果

结果表明,BVJ 含有相当数量的甜菜红素、维生素 C 和各种类型的酚类化合物。因此,BVJ 对 Pb 水平在血液和肝脏中的升高以及肝 DNA 片段化有显著的(p<0.05)预防作用。此外,它显著(p<0.05)改善了铅中毒大鼠中大多数研究的抗氧化和炎症标志物。然而,联合提取物(BVJ-DMSA)在大多数测试参数中显示出协同(组合指数<1)活性。组织病理学结果验证了本研究的生化发现。

结论

BVJ 通过减少 Pb 在血液和肝脏中的积累以及预防 Pb 诱导的氧化应激和炎症,对铅诱导的肝毒性具有强大的保护作用。此外,BVJ 和 DMSA 联合治疗肝毒性显示出协同作用,并减少了 DMSA 诱导的不良反应。因此,BVJ 可以成为一种有前途的抗铅毒性肝保护提取物,其与 DMSA 的联合使用增强了这种作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc17/7466492/708da73d62ce/12906_2020_3056_Fig1_HTML.jpg

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