Chitkara College of Pharmacy, Chitkara University, 140401, Rajpura, Punjab, India.
Chitkara School of Pharmacy, Chitkara University, Baddi, Himachal Pradesh, India.
Naunyn Schmiedebergs Arch Pharmacol. 2022 Nov;395(11):1331-1341. doi: 10.1007/s00210-022-02277-5. Epub 2022 Aug 3.
Renal I/R injury is a severe medical condition contributing to acute kidney injury (AKI), leading to rapid kidney dysfunction and high mortality rates. It is generally observed during renal transplantation, shock, trauma, and urologic and cardiovascular surgery, for which there is no effective treatment. Cell death and damage are commonly linked to I/R. Cell death triggered by iron-dependent lipid peroxidation, such as ferroptosis, has been demonstrated to have a significant detrimental effect in renal IRI models, making it a new type of cell death currently being researched. Ferroptosis is a nonapoptotic type of cell death that occurs when free iron enters the cell and is a critical component of many biological processes. In ferroptosis-induced renal I/R injury, iron chelators such as Deferasirox, Deferiprone, and lipophilic antioxidants are currently suppressed lipid peroxidation Liproxstatin-1 (Lip-1), Ferrostatin-1 along with antioxidants like vitamin and quercetin. Ferroptosis has been considered a potential target for pharmaceutical intervention to alleviate renal IRI-associated cell damage. Thus, this review emphasized the role of ferroptosis and its inhibition in renal IRI. Also, Pharmacological modulation of ferroptosis mechanism in renal I/R injury has been conferred. Graphical abstract.
肾缺血再灌注损伤是一种严重的医学病症，可导致急性肾损伤（AKI），迅速引起肾功能障碍和高死亡率。这种病症通常发生在肾移植、休克、创伤以及泌尿科和心血管手术期间，但目前尚无有效的治疗方法。细胞死亡和损伤通常与 I/R 相关。铁依赖性脂质过氧化引起的细胞死亡（如铁死亡）已被证明在肾 IRI 模型中具有显著的有害作用，使其成为目前正在研究的一种新型细胞死亡方式。铁死亡是一种非凋亡性的细胞死亡形式，当游离铁进入细胞时就会发生铁死亡，它是许多生物学过程的关键组成部分。在铁死亡诱导的肾 I/R 损伤中，铁螯合剂（如地拉罗司、去铁酮和脂溶性抗氧化剂）目前可抑制脂质过氧化反应，如 Liproxstatin-1（Lip-1）、Ferrostatin-1 以及抗氧化剂如维生素和槲皮素。铁死亡已被认为是一种潜在的药物干预靶点，可减轻与肾 IRI 相关的细胞损伤。因此，本综述强调了铁死亡及其抑制在肾 IRI 中的作用。此外，还探讨了肾 I/R 损伤中铁死亡机制的药理学调节。
