Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Life Sci. 2023 Dec 1;334:122209. doi: 10.1016/j.lfs.2023.122209. Epub 2023 Oct 25.
Chronic kidney disease (CKD) is one of the most prevalent chronic diseases and affects between 10 and 14 % of the world's population. The World Health Organization estimates that by 2040, the disease will be fifth in prevalence. End-stage CKD is characterized by renal fibrosis, which can eventually lead to kidney failure and death. Renal fibrosis develops due to multiple injuries and involves oxidative stress and inflammation. In the human body, nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in the expression of antioxidant, anti-inflammatory, and cytoprotective genes, which prevents oxidative stress and inflammation damage. Heme oxygenase (HO-1) is an inducible homolog influenced by heme products and after exposure to cellular stress inducers such as oxidants, inflammatory chemokines/cytokines, and tissue damage as an outcome or downstream of Nrf2 activation. HO-1 is known for its antioxidative properties, which play an important role in regulating oxidative stress. In renal diseases-induced tissue fibrosis and xenobiotics-induced renal fibrosis, Nrf2/HO-1 has been targeted with promising results. This review summarizes these studies and highlights the interesting bioactive compounds that may assist in attenuating renal fibrosis mediated by HO-1 activation. In conclusion, Nrf2/HO-1 signal activation could have a renoprotective effect strategy against CKD caused by oxidative stress, inflammation, and consequent renal fibrosis.
慢性肾脏病（CKD）是最常见的慢性疾病之一，影响全球 10%至 14%的人口。世界卫生组织估计，到 2040 年，该病的发病率将排在第五位。终末期 CKD 的特征是肾纤维化，这最终可能导致肾衰竭和死亡。肾纤维化是由多种损伤引起的，涉及氧化应激和炎症。在人体中，核因子红细胞 2 相关因子 2（Nrf2）在抗氧化、抗炎和细胞保护基因的表达中起着重要作用，可防止氧化应激和炎症损伤。血红素加氧酶（HO-1）是一种诱导型同源物，受血红素产物的影响，并在暴露于细胞应激诱导剂（如氧化剂、炎症趋化因子/细胞因子和组织损伤）后，作为 Nrf2 激活的结果或下游而被激活。HO-1 以其抗氧化特性而闻名，这在调节氧化应激中起着重要作用。在肾脏疾病引起的组织纤维化和外源性物质引起的肾纤维化中，Nrf2/HO-1 已成为研究的靶点，并取得了有前景的结果。本综述总结了这些研究，并强调了可能有助于减轻 HO-1 激活介导的肾纤维化的有趣的生物活性化合物。总之，Nrf2/HO-1 信号的激活可能成为一种针对氧化应激、炎症和随后的肾纤维化引起的 CKD 的肾保护作用策略。
