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木犀草素、表阿夫儿茶精和白花青素对镉诱导的炎症损伤大鼠的潜在影响:一种体外和体内方法。

Potential effect of luteolin, epiafzelechin, and albigenin on rats under cadmium-induced inflammatory insult: and approach.

作者信息

Shahzadi Andleeb, Tariq Nusrat, Sonmez Haktan, Waquar Sulayman, Zahid Ayesha, Javed Muhammad Ahsan, Ashraf Muhammad Yasin, Malik Arif, Ozturk Munir

机构信息

Department of Medical Pharmacology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkiye.

Department of Physiology, M. Islam Medical and Dental College, Gujranwala, Pakistan.

出版信息

Front Chem. 2023 Mar 1;11:1036478. doi: 10.3389/fchem.2023.1036478. eCollection 2023.

Abstract

Cadmium(Cd) an industrial poison present abundantly in the environment, causes human toxicity by an inflammatory process. Chronic exposure of cadmium can cause a number of molecular lesions that could be relevant to oncogenesis, through indirect or epigenetic mechanisms, potentially including abnormal activation of oncogenes and suppression of apoptosis by depletion of antioxidants. As induction of cyclooxygenase (COX)-2 is linked to inflammatory processes, use of luteolin, epiafzelechin, and albigenin alone or in different combinations may be used as anti-inflammatory therapeutic agents. We, herein, performed in silico experiments to check the binding affinity of phytochemicals and their therapeutic effect against COX-2 in cadmium administered rats. Wistar albino rats were given phytochemicals in different combinations to check their anti-inflammatory activities against cadmium intoxication. The level of alanine aminotransferases (ALT), 4-hydroxynonenal (4HNE), 8-hydroxy-2-deoxyguanosine (8-OHdG), tumor necrosis factor-alpha (TNF-α), isoprostanes (IsoP-2α), COX-2, and malondialdehyde (MDA) were estimated with their respective ELISA and spectrophotometric methods. The generated results show that phytocompounds possessed good binding energy potential against COX-2, and common interactive behavior was observed in all docking studies. Moreover, the level of ALT, 4HNE, 8-OHdG, TNF-α, IsoP-2α, malondialdehyde, and COX-2 were significantly increased in rats with induced toxicity compared to the control group, whereas in combinational therapy of phytocompounds, the levels were significantly decreased in the group. Taken together, luteolin, epiafzelechin, and albigenin can be used as anti-inflammatory therapeutic agents for future novel drug design, and thus it may have therapeutic importance against cadmium toxicity.

摘要

镉(Cd)是一种在环境中大量存在的工业毒物,通过炎症过程导致人体中毒。长期接触镉会引发一些分子损伤,这些损伤可能通过间接或表观遗传机制与肿瘤发生相关,潜在地包括癌基因的异常激活以及抗氧化剂耗竭导致的细胞凋亡抑制。由于环氧合酶(COX)-2的诱导与炎症过程相关,单独或不同组合使用木犀草素、表阿夫儿茶精和白坚木辛可能用作抗炎治疗剂。在此,我们进行了计算机模拟实验,以检查植物化学物质的结合亲和力及其对镉处理大鼠中COX-2的治疗效果。给Wistar白化大鼠给予不同组合的植物化学物质,以检查它们对镉中毒的抗炎活性。使用各自的酶联免疫吸附测定法和分光光度法估计丙氨酸转氨酶(ALT)、4-羟基壬烯醛(4HNE)、8-羟基-2'-脱氧鸟苷(8-OHdG)、肿瘤坏死因子-α(TNF-α)、异前列腺素(IsoP-2α)、COX-2和丙二醛(MDA)的水平。生成的结果表明,植物化合物对COX-2具有良好的结合能潜力,并且在所有对接研究中都观察到了常见的相互作用行为。此外,与对照组相比,诱导毒性大鼠中ALT、4HNE、8-OHdG、TNF-α、IsoP-2α、丙二醛和COX-2的水平显著升高,而在植物化合物的联合治疗组中,这些水平显著降低。综上所述,木犀草素、表阿夫儿茶精和白坚木辛可作为未来新型药物设计的抗炎治疗剂,因此可能对镉毒性具有治疗重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b59f/10016615/994700f5cecf/fchem-11-1036478-g001.jpg

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