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

Dubey VK, Patil CR, Kamble SM, Tidke PS, Patil KR, Maniya PJ, Jadhav RB, Patil SP - J Pharmacol Pharmacother (2013)

Bottom Line: It increased GFR and reduced oxidative stress in the kidneys in a dose dependent manner.Significant decrease in the oxidative stress in kidneys indicates the role of anti-oxidant mechanisms in the effects of OA.These results conclusively demonstrate the efficacy of OA in diabetic nephropathy through its possible antioxidant activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Pharmacognosy, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra, India.

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.

No MeSH data available.


Related in: MedlinePlus

Oleanolic acid protects rats kidneys from histological changes induced during diabetic nephropathy Magnification: ×400 Arbritary gradings given in parenthesis by a blinded observer indicate: (+++): Very severe, (++): severe. (+): Only detectable, (-): Absent
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Figure 1: Oleanolic acid protects rats kidneys from histological changes induced during diabetic nephropathy Magnification: ×400 Arbritary gradings given in parenthesis by a blinded observer indicate: (+++): Very severe, (++): severe. (+): Only detectable, (-): Absent

Mentions: As shown in [Figure 1], the histology of kidneys of diabetic rats presented characteristic changes like glomerular thickening, interstitial fibrosis, necrosis, arteriopathy and presence of hyaline casts. Occurrence of such histological changes was less severe in the OA treated rats. In the group treated with OA (60 mg/kg) the kidney histology revealed no other alterations than thickening of the basement membrane that too was less prominent as compared to the diabetic rats.


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

Dubey VK, Patil CR, Kamble SM, Tidke PS, Patil KR, Maniya PJ, Jadhav RB, Patil SP - J Pharmacol Pharmacother (2013)

Oleanolic acid protects rats kidneys from histological changes induced during diabetic nephropathy Magnification: ×400 Arbritary gradings given in parenthesis by a blinded observer indicate: (+++): Very severe, (++): severe. (+): Only detectable, (-): Absent
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643343&req=5

Figure 1: Oleanolic acid protects rats kidneys from histological changes induced during diabetic nephropathy Magnification: ×400 Arbritary gradings given in parenthesis by a blinded observer indicate: (+++): Very severe, (++): severe. (+): Only detectable, (-): Absent
Mentions: As shown in [Figure 1], the histology of kidneys of diabetic rats presented characteristic changes like glomerular thickening, interstitial fibrosis, necrosis, arteriopathy and presence of hyaline casts. Occurrence of such histological changes was less severe in the OA treated rats. In the group treated with OA (60 mg/kg) the kidney histology revealed no other alterations than thickening of the basement membrane that too was less prominent as compared to the diabetic rats.

Bottom Line: It increased GFR and reduced oxidative stress in the kidneys in a dose dependent manner.Significant decrease in the oxidative stress in kidneys indicates the role of anti-oxidant mechanisms in the effects of OA.These results conclusively demonstrate the efficacy of OA in diabetic nephropathy through its possible antioxidant activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Pharmacognosy, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra, India.

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.

No MeSH data available.


Related in: MedlinePlus