Sanajou Davoud, Bahrambeigi Saman, Aslani Somayeh
Department of Biochemistry, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Biochemistry, School of Medicine, Hamedan University of Medical Sciences, Hamedan, Iran.
Iran J Basic Med Sci. 2021 May;24(5):650-656. doi: 10.22038/ijbms.2021.55565.12422.
β-LAPachone (B-LAP) is a natural product with established anti-inflammatory properties. In this study, we investigated the protective potential of B-LAP against diabetic nephropathy in streptozotocin (STZ) induced diabetic mice.
Diabetes induction in mice was carried out by a single intraperitoneal injection of STZ. 2.5 mg/kg/day and 5 mg/kg/day doses of B-LAP were administered orally for twelve weeks and renal histoarchitecture, caspase-3, tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), glutathione peroxidase (GPX), as well as urinary nephrin and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated. Additionally, kidney levels of PI3K, phosphorylated (p)-Akt, p-mTOR, p-CREB, and SIRT1 were assessed in the present investigation.
5 mg/kg B-LAP significantly decreased urinary excretions of nephrin and NGAL. It also mitigated renal TNF-α and MDA levels and simultaneously improved GPX activities. 5 mg/kg B-LAP improved renal function in diabetic mice as indicated by elevated values of creatinine clearance. While B-LAP elevated renal levels of SIRT1, it alleviated PI3K, p-Akt, p-mTOR, and p-CREB levels in the kidneys of diabetic mice.
Collectively, these findings suggest B-LAP as a potential renoprotective agent in STZ-induced diabetic mice probably via modulating the PI3K/Akt/mTOR pathway.
β-拉帕醌（B-LAP）是一种具有抗炎特性的天然产物。在本研究中，我们研究了B-LAP对链脲佐菌素（STZ）诱导的糖尿病小鼠糖尿病肾病的保护潜力。
通过单次腹腔注射STZ诱导小鼠糖尿病。以2.5mg/kg/天和5mg/kg/天的剂量口服B-LAP，持续12周，并评估肾脏组织结构、半胱天冬酶-3、肿瘤坏死因子-α（TNF-α）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GPX）以及尿nephrin和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）。此外，在本研究中还评估了肾脏中PI3K、磷酸化（p）-Akt、p-mTOR、p-CREB和SIRT1的水平。
5mg/kg B-LAP显著降低了nephrin和NGAL的尿排泄量。它还减轻了肾脏TNF-α和MDA水平，同时提高了GPX活性。5mg/kg B-LAP改善了糖尿病小鼠的肾功能，肌酐清除率值升高表明了这一点。虽然B-LAP提高了肾脏中SIRT1的水平，但它减轻了糖尿病小鼠肾脏中PI3K、p-Akt、p-mTOR和p-CREB的水平。
总体而言，这些发现表明B-LAP可能通过调节PI3K/Akt/mTOR途径，成为STZ诱导的糖尿病小鼠潜在的肾脏保护剂。
