Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Bhangagarh, Guwahati, Assam, 781032, India.
Department of Biotechnology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam, 781032, India.
Inflammation. 2016 Oct;39(5):1783-97. doi: 10.1007/s10753-016-0413-4.
Hyperglycaemia-mediated oxidative stress plays an imperative role in the progression of diabetic nephropathy. NF-kB is an important transcription factor in eukaryotes which regulates a diverse array of cellular process, including inflammation, immunological response, apoptosis, growth and development. Increased expression of NF-kB plays a vital role in the pathogenesis of many inflammatory diseases including diabetic nephropathy. Hence, the present study was designed to explore the nephroprotective nature of diosmin by assessing the various biochemical parameters, markers of oxidative stress and proinflammatory cytokine levels in alloxan-induced diabetic Wistar rats. Type 2 diabetes was induced in Wistar rats by single intraperitoneal injection of alloxan (120 mg/kg body weight). Seventy-two hours after the conformation of diabetes (blood glucose level ≥ 250 mg/dl), the rats were segregated into four groups, each group having six animals. Diabetic rats were treated with diosmin at a dose of 50 mg and 100 mg/kg body weight respectively. After the 28th day of treatment, rats were sacrificed, blood serum, plasma and kidney tissue were collected for various biochemical analysis. Inflammatory cytokine levels were measured through ELISA kit. Diosmin treatment produces significant reduction in the blood glucose and plasma insulin level and increases the body weight when compared with diabetic rats. Elevated level of malondialdehyde (MDA) and decrease levels of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and nitric oxide (NO) were significantly restored after 28 days of diosmin treatment. Diosmin treatment group also restores the normal architecture of the kidney tissue which was confirmed by histopathological examination. Moreover, oral administration of diosmin shows a significant normalization in the level of NF-kB, proving its pivotal role in maintaining renal function. The above ameliorative effects were more pronounced with diosmin at a dose of 100 mg/kg body weight. The above results permit us to conclude that treatment with diosmin halts hyperglycaemia-mediated oxidative stress and decline in pro-inflammatory cytokines and thus has beneficial anti-diabetic activity.
高血糖介导的氧化应激在糖尿病肾病的进展中起着至关重要的作用。NF-κB 是真核生物中一种重要的转录因子，调节着包括炎症、免疫反应、细胞凋亡、生长和发育在内的多种细胞过程。NF-κB 的表达增加在许多炎症性疾病的发病机制中起着至关重要的作用，包括糖尿病肾病。因此，本研究旨在通过评估丙烯醛诱导的糖尿病 Wistar 大鼠的各种生化参数、氧化应激标志物和促炎细胞因子水平，探讨地奥司明的肾保护作用。通过单次腹腔注射丙烯醛（120mg/kg 体重）诱导 Wistar 大鼠 2 型糖尿病。在糖尿病确证后 72 小时（血糖水平≥250mg/dl），将大鼠分为 4 组，每组 6 只。糖尿病大鼠分别用地奥司明 50mg 和 100mg/kg 体重治疗。治疗 28 天后，处死大鼠，采集血清、血浆和肾脏组织进行各种生化分析。通过 ELISA 试剂盒测量炎性细胞因子水平。与糖尿病大鼠相比，地奥司明治疗可显著降低血糖和血浆胰岛素水平，增加体重。28 天后，地奥司明治疗可显著恢复丙二醛（MDA）水平升高和超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、还原型谷胱甘肽（GSH）和一氧化氮（NO）水平降低。地奥司明治疗组还可恢复肾脏组织的正常结构，这通过组织病理学检查得到证实。此外，地奥司明的口服给药可显著使 NF-κB 水平正常化，证明其在维持肾功能方面的关键作用。地奥司明 100mg/kg 体重组的上述改善作用更为明显。上述结果使我们得出结论，地奥司明治疗可阻止高血糖介导的氧化应激和促炎细胞因子水平下降，从而具有有益的抗糖尿病活性。
