Yarmohammadi Akram, Arkan Elham, Najafi Houshang, Abbaszadeh Fatemeh, Rashidi Khodabakhsh, Piri Sana, Fakhri Sajad
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):4491-4502. doi: 10.1007/s00210-024-03543-4. Epub 2024 Nov 4.
Acute kidney injury (AKI) is a sudden onset of renal injury that occurs within a few hours or days. Ischemia-reperfusion (IR) is a major cause of AKI. There are multiple dysregulated mechanisms behind the pathogenesis of AKI and IR which urges the need for finding multi-targeting therapies. Natural products are multi-targeting agents with promising sources of anti-inflammation, antioxidant, and antiapoptosis. Among them, astaxanthin (AST) is a keto-carotenoid with a high antioxidant potential. Using solid lipid nanoparticles (SLNs) as a novel formulation of AST helps to increase its efficacy and reduce side effects against AKI. After SLN preparation and loading of AST, the physicochemical properties were evaluated, using scanning electron microscopy (SEM) and dynamic light scattering (DLS) tests. For the in vivo study, 28 rats were divided into four groups, including sham, ischemia/reperfusion (I/R), and groups receiving protective and daily doses of AST-SLN (5 and 10 mg/kg, i.p.) during all 5 days before ischemia. Exactly 24 h after ischemia, kidneys were isolated for histological studies, and also, serum levels of catalase (CAT), glutathione (GSH), nitrite, blood urea, and creatinine were measured. The results indicated that intraperitoneal administration of SLN-AST reduced oxidative stress by decreasing serum nitrite levels, while increasing CAT and GSH. SLN-AST also improved renal function by decreasing serum urea and creatinine and preventing tissue damage. Therefore, SLN-AST could be a hopeful adjuvant candidate to prevent AKI by modulating renal function, preventing tissue damage, and through antioxidant mechanisms.
急性肾损伤(AKI)是指在数小时或数天内突然发生的肾损伤。缺血再灌注(IR)是AKI的主要原因。AKI和IR发病机制背后存在多种失调机制,这促使人们寻找多靶点治疗方法。天然产物是具有抗炎、抗氧化和抗凋亡潜力的多靶点药物。其中,虾青素(AST)是一种具有高抗氧化潜力的酮类胡萝卜素。使用固体脂质纳米粒(SLN)作为AST的新型制剂有助于提高其疗效并减少对AKI的副作用。在制备SLN并负载AST后,使用扫描电子显微镜(SEM)和动态光散射(DLS)测试评估其物理化学性质。在体内研究中,将28只大鼠分为四组,包括假手术组、缺血/再灌注(I/R)组以及在缺血前5天内接受保护性和每日剂量AST-SLN(5和10 mg/kg,腹腔注射)的组。缺血24小时后,分离肾脏进行组织学研究,并测量血清中过氧化氢酶(CAT)、谷胱甘肽(GSH)、亚硝酸盐、血尿素和肌酐的水平。结果表明,腹腔注射SLN-AST可通过降低血清亚硝酸盐水平来减轻氧化应激,同时增加CAT和GSH。SLN-AST还可通过降低血清尿素和肌酐水平并防止组织损伤来改善肾功能。因此,SLN-AST可能是一种有希望的辅助药物,可通过调节肾功能、防止组织损伤以及通过抗氧化机制来预防AKI。