El-Aarag Bishoy, Attia Alshaimaa, Zahran Magdy, Younes Ali, Tousson Ehab
Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt.
Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt.
Saudi J Biol Sci. 2021 Nov;28(11):6384-6395. doi: 10.1016/j.sjbs.2021.07.014. Epub 2021 Jul 14.
The present study aimed, for the first time, to examine the biochemical effects of new phthalimide analog, 2-[2-(2-Bromo-1-ethyl-1H-indol-3-yl) ethyl]-1H-isoindole-1,3(2H)-dione, compared to thalidomide drug against liver injury induced in mice. Carbon tetrachloride was intraperitoneal injected in mice for 6 consecutive weeks at a dose of 0.4 mL/kg twice a week for liver injury induction. Histopathological examination, levels of malondialdehyde, nitric oxide, and antioxidant enzymes were determined. Additionally, the protein levels of vascular endothelial growth factor, proliferating cell nuclear protein, tumor necrosis factor-alfa, nuclear factor kappa B-p65, B-cell lymphoma-2, and cysteine-aspartic acid protease-3 were determined. Results revealed that the treatment with phthalimide analog improved the detected liver damage and presented an obvious antioxidant activity through decreasing malondialdehyde and nitric oxide levels accompanied by increasing the levels of the antioxidant enzymes. Furthermore, the analog exhibited an effective inhibitory activity towards the studied protein expressions in liver tissues. Moreover, the B-cell lymphoma-2 protein level was increased while the cysteine-aspartic acid protease-3 level was suppressed after the treatment with phthalimide analog. Together, these results propose that phthalimide analog can ameliorate carbon tetrachloride-induced liver injury in mice through its potent inhibition mediating effect in oxidative stress, inflammation, and apoptosis mechanisms.
本研究首次旨在检验新型邻苯二甲酰亚胺类似物2-[2-(2-溴-1-乙基-1H-吲哚-3-基)乙基]-1H-异吲哚-1,3(2H)-二酮与沙利度胺药物相比，对小鼠肝损伤的生化作用。将四氯化碳以0.4 mL/kg的剂量每周两次腹腔注射给小鼠，连续6周以诱导肝损伤。进行了组织病理学检查，测定了丙二醛、一氧化氮和抗氧化酶的水平。此外，还测定了血管内皮生长因子、增殖细胞核蛋白、肿瘤坏死因子-α、核因子κB-p65、B细胞淋巴瘤-2和半胱天冬酶-3的蛋白水平。结果显示，邻苯二甲酰亚胺类似物治疗改善了检测到的肝损伤，并通过降低丙二醛和一氧化氮水平，同时提高抗氧化酶水平，呈现出明显的抗氧化活性。此外，该类似物对肝组织中研究的蛋白表达表现出有效的抑制活性。而且，用邻苯二甲酰亚胺类似物治疗后，B细胞淋巴瘤-2蛋白水平升高，而半胱天冬酶-3水平受到抑制。总之，这些结果表明，邻苯二甲酰亚胺类似物可通过其在氧化应激、炎症和凋亡机制中的有效抑制介导作用，改善四氯化碳诱导的小鼠肝损伤。
