文章基本信息

标题：The protective effect of isoliquiritigenin against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling as one key mechanism
本地全文：下载
作者：Wahidah H. Al-Qahtani ; Ghedeir M. Alshammari ; Mohammad A. Alshuniaber 等
期刊名称：Journal of King Saud University - Science
印刷版ISSN：1018-3647
出版年度：2022
卷号：34
期号：6
页码：1-13
DOI：10.1016/j.jksus.2022.102165
语种：English
出版社：Elsevier
摘要：AbstractObjectivesThis study aimed to evaluate if the protective effect of Isoliquiritigenin (ISL) against doxorubicin-induced nephropathy in rats entails activation of Nrf2 signaling.MethodsAdult male Wistart rats were treated as control, ISL, DOX, DOX, and ISL + DOX + ISL + Nrf2 inhibitor (brusatol) (n = 8/group). Treatments with ISL (25 mg//kg, oral) were carried out 10 days before and 10 days after the single dose of DOX (15 mg/kg, i.p).ResultsTreatment with ISL attenuated the glomerular and tubular damage and reduced interstitial fibrosis and collagen accumulation in the kidneys of DOX-intoxicated animals. It also increased urinary flow and volume, stimulated urinary creatinine excretion, and decreased albumin excretion. These effects were associated with high transcription of Bcl2, suppression of ROS, MDA, and inflammatory cytokines production (i.e., TNF-α, IL-6, and IL-1β), downregulation of apoptotic markers (Bax and caspase-3/9), TGF-β1, Collagen I/III. Besides, ISL stimulated renal expression, translation, and nuclear localization of Nrf2, as well as levels of GSH and SOD, independent of keap-1. All these effects afforded by ISL were reversed by suppressing Nrf2 with brusatol.ConclusionPre-treatment with ISL is an effective strategy to alleviate DOX-induced nephropathy in rats by stimulating the Nrf2/antioxidant axis, which encourages further pre-clinical studies.
关键词：KeywordsIsoliquiritigeninDoxorubicinNrf2AntioxidantKidney