Oleanolic acid prevents progression of streptozotocin induced diabetic nephropathy and protects renal microstructures in Sprague Dawley rats

Abstract

Objective:To study the effect of oleanolic acid (OA) on streptozotocin induced diabetic nephropathy in Sprague Dawley rats.Materials and Methods:Four weeks after intra-peritoneal injection of streptozotocin (STZ; 55 mg/kg), the rats with proteinuria were grouped as: Control (non-diabetic, treated orally with vehicle), diabetic control (treated orally with vehicle) and three diabetic groups receiving 20, 40 and 60 mg/kg/day oral doses of OA. At the end of 8 weeks, urine and serum samples from the rats were processed for determination of creatinine, BUN and GFR. The kidney samples were processed for determination of weight changes, oxidative stress related parameters like catalase, superoxide dismutase and reduced glutathione levels. A part of one kidney from each rat was used for transmission electron microscopy (TEM).Result:As evident in TEM, OA inhibited the nephropathy induced alterations in podocyte integrity, basement membrane thickness and spacing between the podocytes at 60 mg/kg dose. It increased GFR and reduced oxidative stress in the kidneys in a dose dependent manner. These findings conclusively demonstrate the efficacy of OA in diabetic nephropathy. Significant decrease in the oxidative stress in kidneys indicates the role of anti-oxidant mechanisms in the effects of OA. However, OA is known to act through multiple mechanisms like inhibition of the generation of advanced glycation end products and improving the insulin secretion. These mechanisms might have contributed to its efficacy.Conclusion:These results conclusively demonstrate the efficacy of OA in diabetic nephropathy through its possible antioxidant activity.

Evaluation of Effect of Montelukast in the Model of Streptozotocin Induced Diabetic Nephropathy in Rats

“…FBG, BUN, serum creatinine and urine microalbumin. [ 21 35 36 37 38 39 40 41 42 43 ] In our study, baseline FBG levels of the rats were found to be comparable across all the groups and were within the normal range. There was a dramatic rise in FBG after one week of STZ administration indicating successful induction of diabetes.…”

“…Some researchers reported a decrease in weight, while others have reported an increase or no significant change in kidney weight. [ 33 34 35 ] In our study, kidney volume and weight were higher in the Enalapril group compared to the vehicle control group. However, there was no statistically significant difference in mean kidney weights among the different groups.…”

“…A study conducted by Dubey VK et al . [ 35 ] showed significant albuminuria after four weeks of administration of STZ. In our study too, the vehicle control group showed higher microalbuminuria and Enalapril as well as both the Montelukast groups offered protection against it.…”

Traditional Uses, Phytochemistry, and Pharmacology ofOlea europaea(Olive)

“…This compound exhibited excellent inhibitory activities in vitro against α -amylase and lipase enzymes [ 117 ]. Recently, the effect of oleanolic acid on streptozotocin-induced diabetic neuropathy in Sprague Dawley rats has been studied [ 149 ]. The rats were divided into control group and diabetic group and were daily treated with 20, 40, and 60 mg/Kg doses of oleanolic acid up to four weeks.…”

The Effect and Mechanism of Oleanolic Acid in the Treatment of Metabolic Syndrome and Related Cardiovascular Diseases

“…In addition, OA was able to enhance the antioxidant function of mitochondria by increasing the expression of glutathione peroxidase 4 (Gpx4) and SOD [ 75 ]. Furthermore, OA was reported to improve the mitochondrial ultrastructure and function and antioxidant capacity by inhibiting MDA and ROS levels, as well as increasing CAT, SOD, and glutathione peroxidase (GSH-px) in diabetic rats [ 11 , 76 , 77 ].…”