Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Nutrition. 2022 Oct;102:111732. doi: 10.1016/j.nut.2022.111732. Epub 2022 May 14.
Doxorubicin (Dox) is an indispensable chemotherapeutic agent associated with damaging cardiotoxicity. Baicalin (BA) is a flavonoid, extracted from the medicinal plant Scutellariae baicalensis Georgi. BA is well known for its anti-inflammatory and antioxidant effects. Our study investigated the potential effect of BA in attenuating Dox-induced cardiotoxicity. To this end, male Swiss albino mice were given BA (100 mg/kg/d, orally) for 4 wk and were challenged with Dox (six intraperitoneal doses, each 2.5 mg/kg, every other day with a final cumulative dose of 15 mg/kg). Serum activities of cardiac biomarkers (cardiac troponin-I, creatine kinase-membrane bound, lactate dehydrogenase, and aspartate aminotransferase) were assessed along with the histopathological examination of the heart tissues. Gene expression of Toll-like receptor 4 (TLR4) was analyzed by quantitative reverse transcription real-time polymerase chain reaction. Analysis of the protein levels of β-catenin and nuclear factor-κB (NF-κB) was done immunohistochemically. Cardiac Dickkopf-1 (DKK1) and interleukin-1beta (IL-1β) were quantified by enzyme-linked immuno-sorbent assay. Cardiac levels of reduced glutathione (GSH) and malondialdehyde (MDA) were detected spectrophotometrically. Pretreatment with BA significantly prevented Dox-induced elevation of serum activities of cardiac biomarkers and alterations to the heart. Moreover, BA suppressed the gene overexpression of cardiac TLR4 and subsequently prevented Dox-induced elevation of both cardiac NF-κB and IL-1β. BA also significantly reduced the cardiac levels of DKK1 and elevated the level of β-catenin. Dox-induced elevation of MDA and reduction of GSH were reversed by BA. BA exhibited a novel cardioprotective effect against Dox-induced cardiotoxicity. The cardioprotective effect was indicated through the inhibition of the inflammatory TLR4/NF-κB pathway and the activation of the protective Wnt/β-catenin pathway by the suppression of DKK1.
阿霉素（Dox）是一种不可或缺的化疗药物，与心脏毒性损伤有关。黄芩苷（BA）是一种黄酮类化合物，从药用植物黄芩中提取。BA 以其抗炎和抗氧化作用而闻名。我们的研究调查了 BA 减轻 Dox 诱导的心脏毒性的潜在作用。为此，雄性瑞士白化病小鼠口服 BA（100mg/kg/d，连续 4 周），并用 Dox（六次腹腔注射，每次 2.5mg/kg，每隔一天一次，累积终剂量为 15mg/kg）进行挑战。评估血清心脏生物标志物（肌钙蛋白 I、肌酸激酶膜结合物、乳酸脱氢酶和天冬氨酸氨基转移酶）的活性，以及心脏组织的组织病理学检查。通过定量逆转录实时聚合酶链反应分析 Toll 样受体 4（TLR4）的基因表达。用免疫组织化学法分析 β-连环蛋白和核因子-κB（NF-κB）的蛋白水平。通过酶联免疫吸附试验定量心脏 Dickkopf-1（DKK1）和白细胞介素-1β（IL-1β）。用分光光度法检测心脏还原型谷胱甘肽（GSH）和丙二醛（MDA）的水平。BA 预处理显著防止 Dox 诱导的血清心脏生物标志物升高和心脏改变。此外，BA 抑制心脏 TLR4 的基因过表达，并随后防止 Dox 诱导的心脏 NF-κB 和 IL-1β升高。BA 还显著降低心脏 DKK1 水平并升高 β-连环蛋白水平。BA 逆转了 Dox 诱导的 MDA 升高和 GSH 降低。BA 通过抑制炎症 TLR4/NF-κB 途径和通过抑制 DKK1 激活保护性 Wnt/β-连环蛋白途径表现出对 Dox 诱导的心脏毒性的新型心脏保护作用。
