Diosmin Modulates the NF-kB Signal Transduction Pathways and Downregulation of Various Oxidative Stress Markers in Alloxan-Induced Diabetic Nephropathy

Abstract

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.

Advances in early biomarkers of diabetic nephropathy

“…16 In agreement with GST, animal experiments on LPO have yielded the same results. 17,18 In addition, genetic investigation also found that knockout of GST coding genes can lead to decreased GST levels and increased malondialdehyde (MDA) levels, an important biomarker of LPO, demonstrating that GST has an effect against oxidative stress. 19 Human research was consistent with the experimental studies above.…”

Efeito antioxidante da diosmina: revisão integrativa

“…A caracterização dos estudos e os resultados acerca da Diosmina foram relatados e expostos na Figura 1. [16][17][18][19][20][21][22][23] , contribuindo para a redução das lesões cardíacas, hepáticas e renais induzidas em muitos modelos de experimentação animal (Tabela 1).…”

Role of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy

“…For type 2 diabetes rats, similarly, upregulation of malondialdehyde and downregulation of antioxidant enzymes, such as superoxide dismutase and glutathione, were observed in diabetes rat kidney. And, restoration of these enzymes halted hyperglycemia-induced oxidative stress and maintained renal function [14]. Moreover, it is not difficult to obtain similar evidence from clinical studies [15–17].…”