Quercetin, an Anti‐oxidant Bioflavonoid, Attenuates Diabetic Nephropathy in Rats

Abstract

1. Diabetic nephropathy is an important microvascular complication and one of the main causes of end-stage renal disease. Many in vivo and in vitro studies have indicated that oxidative stress is one of the major pathophysiological mechanisms involved in the development of diabetic nephropathy. In the present study, we examined the effect of an anti-oxidant bioflavonoid quercetin on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. 2. Diabetes was induced in Sprague-Dawley rats with a single intravenous injection of STZ (45 mg/kg). Four weeks after STZ injection, quercetin (10 mg/kg per day) was given orally for 4 weeks in both control and diabetic rats. Plasma glucose levels and bodyweights were measured at 4 and 8 weeks after the STZ injection. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The renal oxidative stress marker malonaldehyde, glutathione levels and the anti-oxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. 3. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in bodyweight compared with age-matched control rats. After 8 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Treatment with quercetin significantly attenuated renal dysfunction and oxidative stress in diabetic rats. 4. These results confirm the role of oxidative stress in the development of diabetic nephropathy and point to the possible anti-oxidative mechanism being responsible for the nephroprotective action of quercetin.

Quercetin suppresses NF-κB and MCP-1 expression in a high glucose-induced human mesangial cell proliferation model

“…Protective effects of quercetin in diabetes mellitus and DN have also been reported in rat models (12)(13)(14). Our data showed that quercetin treatment at 40 µM led to smaller cells with irregular shapes, larger gaps between adjacent cells, and weakened cell adhesion (Fig.…”

“…Protective effects of quercetin in diabetes mellitus and DN have also been reported in rat models (10)(11)(12). In addition, the protective effects of quercetin have been observed in a streptozotocin (STZ)-induced model of diabetes mellitus (11)(12)(13)(14). Furthermore, Kim et al (15) reported that dietary quercetin attenuated fasting and postprandial hyperglycemia.…”

Preventive Effects of Flavonoids on Alloxan-Induced Diabetes Mellitus in Rats

“…( Mira et al 2002;Anjaneyulu and Chopra 2004). On the other hand, it was found that chrysin had only a moderate antioxidant effect and almost no metal chelatory properties (Kubo et al 2000;Furusawa et al 2005).…”

“…Certain studies have found increased lipid peroxides or ROS and oxidative stress (or both) in different animal models of diabetes (Anjaneyulu and Chopra 2004;Mehta et al 2006). However, the results in clinical practice are not unequivocal and the usefulness of antioxidant therapy in diabetic patients is not convincing (Newsholme et al 2007).…”

“…From the results of clinical studies (Knekt et al 2002) it is evident without any doubt that the reduction of hyperglycaemia is the most important factor in the prevention of chronic microvascular complications of diabetes mellitus (retinopathy, nepropathy, neuropathy and diabetic foot) as well as in the prevention of the accelerated atherosclerosis-related conditions (myocardial infarction, stroke). Several researchers have demonstrated that flavonoids act as reducers of hyperglycaemia (Anjaneyulu and Chopra 2004;Dene et al 2005) and there is reduced non-enzymatic glycation of proteins in animals. Studies with flavonoids are underway to further elucidate their mechanism of action.…”