Hellal Doaa, El-Khalik Sarah Ragab Abd, Arakeep Heba M, Radwan Doaa A, Abo Safia Hend S, Farrag Eman A E
Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura, 31516, Egypt.
Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May;398(5):5593-5609. doi: 10.1007/s00210-024-03620-8. Epub 2024 Nov 23.
Nonsteroidal anti-inflammatory drug (NSAID)-induced kidney injury is one of the most common causes of renal failure. The exact pathogenesis of NSAID induced kidney injury is not fully known and the treatment is still challenging. Artemisinin (ART) gains more attention by its potent biological activities in addition to its antimalarial effect. In our research, we evaluated the preventive and therapeutic effects of ART in Diclofenac (DIC) induced kidney injury through its effect on mitochondria and regulation of sirtuin 3 (SIRT3). Thirty adult male Sprague Dawley rats were divided into five groups: control, ART, DIC, DIC + ART prophylactic, and DIC followed + ART therapeutic groups. At the end of the study, animals were scarified and the following parameters were evaluated: serum urea and creatinine, renal malondialdehyde (MDA), superoxide dismutase (SOD) and nitrate. SIRT3 was detected by western blotting and real-time PCR. Mitochondrial related markers (PGC-1α, Drp1, and mitochondrial ATP) were detected by immunoassay. Caspase-3 and LC3 II expression in kidney tissues were demonstrated by immune-histochemical staining. The kidney specimens were stained for H&E and PAS special stain. Electron microscopy was done to detect mitochondrial morphology. ART improved renal function test, oxidative stress, SIRT3 level, mitochondrial function, LC3 II expression and decrease caspase-3. Histopathological examination confirmed ART alleviation as determined by light or electron microscopy. ART can modulate biochemical and pathological changes in DIC-induced kidney injury and can be considered a new possible therapeutic approach for DIC-induced kidney injury through its effect on SIR3 and maintenance of mitochondrial homeostasis.
非甾体抗炎药（NSAID）引起的肾损伤是肾衰竭最常见的原因之一。NSAID 所致肾损伤的确切发病机制尚未完全明确，治疗仍具有挑战性。青蒿素（ART）除了具有抗疟作用外，其强大的生物学活性也受到了更多关注。在我们的研究中，我们通过评估 ART 对线粒体的影响以及对沉默调节蛋白 3（SIRT3）的调控，来研究其对双氯芬酸（DIC）诱导的肾损伤的预防和治疗作用。将 30 只成年雄性 Sprague Dawley 大鼠分为五组：对照组、ART 组、DIC 组、DIC + ART 预防组和 DIC 后 + ART 治疗组。在研究结束时，处死动物并评估以下参数：血清尿素和肌酐、肾丙二醛（MDA）、超氧化物歧化酶（SOD）和硝酸盐。通过蛋白质免疫印迹法和实时聚合酶链反应检测 SIRT3。通过免疫测定法检测线粒体相关标志物（PGC-1α、Drp1 和线粒体 ATP）。通过免疫组织化学染色显示肾组织中半胱天冬酶 -3 和 LC3 II 的表达。对肾标本进行苏木精 - 伊红（H&E）染色和过碘酸雪夫（PAS）特殊染色。进行电子显微镜检查以检测线粒体形态。ART 改善了肾功能测试、氧化应激、SIRT3 水平、线粒体功能、LC3 II 表达并降低了半胱天冬酶 -3。组织病理学检查证实，通过光镜或电镜观察，ART 具有减轻损伤的作用。ART 可以调节 DIC 诱导的肾损伤中的生化和病理变化，并且通过其对 SIR3 的影响和维持线粒体稳态，可被视为 DIC 诱导的肾损伤的一种新的可能治疗方法。
