关于 -丁基对苯二酚的肝保护活性的研究。

and Studies of the Hepatoprotective Activity of -Butylhydroquinone.

机构信息

Biomedical Science Laboratory, Clinical Chemistry, Faculty of Professional Studies Huasteca Zone, Autonomous University of San Luis Potosi, Ciudad Valles 79060, San Luis Potosi, Mexico.

Pharmacobiological Sciences, Faculty of Chemical Sciences, Autonomous University of San Luis Potosi, San Luis Potosi 78210, Mexico.

出版信息

Int J Mol Sci. 2023 Dec 29;25(1):475. doi: 10.3390/ijms25010475.

DOI:10.3390/ijms25010475

PMID:38203648

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10779046/

Abstract

-butylhydroquinone (TBHQ) is a synthetic food antioxidant with biological activities, but little is known about its pharmacological benefits in liver disease. Therefore, this work aimed to evaluate TBHQ during acute liver damage induced by CCl (24 h) or BDL (48 h) in Wistar rats. It was found that pretreatment with TBHQ prevents 50% of mortality induced by a lethal dose of CCl (4 g/kg, i.p.), and 80% of BDL+TBHQ rats survived, while only 50% of the BDL group survived. Serum markers of liver damage and macroscopic and microscopic (H&E staining) observations suggest that TBHQ protects from both hepatocellular necrosis caused by the sublethal dose of CCl (1.6 g/kg, i.p.), as well as necrosis/ductal proliferation caused by BDL. Additionally, online databases identified 49 potential protein targets for TBHQ. Finally, a biological target candidate (Keap1) was evaluated in a proof-of-concept in silico molecular docking assay, resulting in an interaction energy of -5.5491 kcal/mol, which was higher than RA839 and lower than monoethyl fumarate (compounds known to bind to Keap1). These findings suggest that TBHQ increases the survival of animals subjected to CCl intoxication or BDL, presumably by reducing hepatocellular damage, probably due to the interaction of TBHQ with Keap1.

摘要

叔丁基对苯二酚（TBHQ）是一种具有生物活性的合成食品抗氧化剂，但关于其在肝病中的药理作用知之甚少。因此，本工作旨在评价 TBHQ 在 Wistar 大鼠 CCl（24 小时）或 BDL（48 小时）诱导的急性肝损伤中的作用。结果发现，TBHQ 预处理可预防致死剂量 CCl（4 g/kg，腹腔注射）诱导的 50%的死亡率，80%的 BDL+TBHQ 大鼠存活，而 BDL 组仅存活 50%。血清肝损伤标志物以及大体和微观（H&E 染色）观察表明，TBHQ 可预防亚致死剂量 CCl（1.6 g/kg，腹腔注射）引起的肝细胞坏死以及 BDL 引起的坏死/胆管增生。此外，在线数据库鉴定出 49 个 TBHQ 的潜在蛋白靶标。最后，在基于计算机的分子对接虚拟筛选实验中评估了一个生物靶标候选物（Keap1），其相互作用能为-5.5491 kcal/mol，高于 RA839，低于富马酸单乙酯（已知与 Keap1 结合的化合物）。这些发现表明，TBHQ 通过减少肝细胞损伤，增加了 CCl 中毒或 BDL 动物的存活率，这可能是由于 TBHQ 与 Keap1 的相互作用。