Oleanolic acid prevents progression of streptozotocin induced diabetic nephropathy and protects renal microstructures in Sprague Dawley rats - PubMed (original) (raw)
Oleanolic acid prevents progression of streptozotocin induced diabetic nephropathy and protects renal microstructures in Sprague Dawley rats
Vishal K Dubey et al. J Pharmacol Pharmacother. 2013 Jan.
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.
Keywords: Electron microscopy; glomerular basement membrane; pentacyclic triterpenoid; podocytes.
Conflict of interest statement
Conflict of Interest: None declared.
Figures
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
Figure 2
Oleanolic acid protects rats kidneys from ultramicroscopic changes associated with diabetic nephropathy. Magnification: 5600×, BM : Basement membrane, PC : podocyte, MV : Microvasculature
Figure 3
Oleanolic acid ameliorated the symptoms of streptozotocin induced diabetes in rats
Similar articles
- Oleanolic acid and its analogues: promising therapeutics for kidney disease.
Pan D, Qu Y, Shi C, Xu C, Zhang J, Du H, Chen X. Pan D, et al. Chin Med. 2024 May 30;19(1):74. doi: 10.1186/s13020-024-00934-w. Chin Med. 2024. PMID: 38816880 Free PMC article. Review. - Attenuation of diabetic nephropathy in streptozotocin-induced diabetic rats by Punica granatum Linn. leaves extract.
Mestry SN, Dhodi JB, Kumbhar SB, Juvekar AR. Mestry SN, et al. J Tradit Complement Med. 2016 Jul 13;7(3):273-280. doi: 10.1016/j.jtcme.2016.06.008. eCollection 2017 Jul. J Tradit Complement Med. 2016. PMID: 28725620 Free PMC article. - Quercetin, an anti-oxidant bioflavonoid, attenuates diabetic nephropathy in rats.
Anjaneyulu M, Chopra K. Anjaneyulu M, et al. Clin Exp Pharmacol Physiol. 2004 Apr;31(4):244-8. doi: 10.1111/j.1440-1681.2004.03982.x. Clin Exp Pharmacol Physiol. 2004. PMID: 15053821 - Astragaloside IV ameliorates diabetic nephropathy involving protection of podocytes in streptozotocin induced diabetic rats.
Chen J, Chen Y, Luo Y, Gui D, Huang J, He D. Chen J, et al. Eur J Pharmacol. 2014 Aug 5;736:86-94. doi: 10.1016/j.ejphar.2014.04.037. Epub 2014 May 6. Eur J Pharmacol. 2014. PMID: 24809932 - Protective effects of tacrolimus on podocytes in early diabetic nephropathy in rats.
Peng T, Chang X, Wang J, Zhen J, Yang X, Hu Z. Peng T, et al. Mol Med Rep. 2017 May;15(5):3172-3178. doi: 10.3892/mmr.2017.6354. Epub 2017 Mar 22. Mol Med Rep. 2017. PMID: 28339051
Cited by
- Oleanolic acid and its analogues: promising therapeutics for kidney disease.
Pan D, Qu Y, Shi C, Xu C, Zhang J, Du H, Chen X. Pan D, et al. Chin Med. 2024 May 30;19(1):74. doi: 10.1186/s13020-024-00934-w. Chin Med. 2024. PMID: 38816880 Free PMC article. Review. - Evaluation of Effect of Montelukast in the Model of Streptozotocin Induced Diabetic Nephropathy in Rats.
Kokate D, Marathe P. Kokate D, et al. Indian J Endocrinol Metab. 2024 Jan-Feb;28(1):47-54. doi: 10.4103/ijem.ijem_414_22. Epub 2024 Feb 26. Indian J Endocrinol Metab. 2024. PMID: 38533280 Free PMC article. - The Effect and Mechanism of Oleanolic Acid in the Treatment of Metabolic Syndrome and Related Cardiovascular Diseases.
Luo Q, Wei Y, Lv X, Chen W, Yang D, Tuo Q. Luo Q, et al. Molecules. 2024 Feb 6;29(4):758. doi: 10.3390/molecules29040758. Molecules. 2024. PMID: 38398510 Free PMC article. Review. - Nephroprotective effect of Vanillic acid in STZ-induced diabetic rats.
Kumari S, Kamboj A, Wanjari M, Sharma AK. Kumari S, et al. J Diabetes Metab Disord. 2021 Apr 3;20(1):571-582. doi: 10.1007/s40200-021-00782-7. eCollection 2021 Jun. J Diabetes Metab Disord. 2021. PMID: 34222078 Free PMC article. - Protosappanin-A and oleanolic acid protect injured podocytes from apoptosis through inhibition of AKT-mTOR signaling.
Zheng J, Zhang S, Chen H, Cai X, Zhang C, Li S, Zhou Y, Shang J, Liang S, Yao F. Zheng J, et al. Cell Biol Int. 2020 Jan;44(1):189-199. doi: 10.1002/cbin.11218. Epub 2019 Sep 8. Cell Biol Int. 2020. PMID: 31441181 Free PMC article.
References
- Liby KT, Yore MM, Sporn MB. Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nat Rev Cancer. 2007;7:357–69. - PubMed
- Dzubak P, Hajduch M, Vydra D, Hustova A, Kvasnica M, Biedermann D, et al. Pharmacological activities of natural triterpenoids and their therapeutic implications. Nat Prod Rep. 2006;23:394–441. - PubMed
- Sporn MB, Liby KT, Yore MM, Suh N, Albini A, Honda T, et al. Platforms and networks in triterpenoid pharmacology. Drug Dev Res. 2007;68:174–82.
- Liu J. Oleanolic acid and urosolic acid: Research perspectives. J Ethnopharmacol. 2005;100:92–4. - PubMed
- Sultana N, Ata A. Oleanolic acid and related derivatives as medicinally important compounds. J Enzyme Inhib Med Chem. 2008;23:739–56. - PubMed
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials