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PO1-5-2

Apigenin ameliorates streptozotocin induced diabetic nephropathy in rats

[Speaker] Dharamvir S. Arya:1
[Co-author] Salma Malik:1, Jagriti Bhatia:1
1:Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi, India

Background
Diabetic nephropathy is a seious complication of diabetes mellitus. Inflammation, oxidative stress and fibrosis have been implicated in the progression of diabetic nephropathy. Apigenin, a bioflavanoid, possesses anti-inflammatory, antifibrotic anti-diabetic properties. Hence Apigenin was evaluated in an experimental model of Streptozotocin (STZ) induced diabetic rats to study the efficacy of apigenin in halting the progression of diabetic nephropathy.

Methods
The study protocol was approved by the Institutional Animal Ethics Committee (IAEC no. 671/IAEC/12). Male albino wistar rats were divided into control, diabetic control, apigenin treatment groups (5, 10 and 20mg/kg p.o.), ramipril treatment group (2mg/kg p.o.) and apigenin per se (20mg/kg p.o.). The rats were administered drug treatment for 8 months. All groups except control and per se were administered single injection of STZ (55mg/kg i.p.) to induce diabetes mellitus.

Results
The diabetic rats were treated with apigenin (20mg/kg) exhibited reduced oxidative stress and renal dysfunction. Also, the renal tissue had decreased fibronectin, transforming growth factor beta - 1 and type IV collagen levels thereby suggesting reduction in the degree of fibrosis. Further, the histopathological examination of kidney also revealed reduction in collagen deposition, inflammation and glomwrulosclerosis in renal tissue of rats in comparison to the diabetic control rats.In addition, by inhibiting Mitogen Activated Protein Kinase (MAPK) activation, apigenin also suppressed inflammation.This was evident from decreased renal expression of various inflammatory proteins like TNF-alpha, IL-6 and NF-kappa B. Also, there was decreased expression of pro-apoptotic proteins like Bax and Caspase-3 and increased expression of anti-apoptotic protein Bcl-2. Furthermore, the renal protection observed with apigenin (20mg/kg) was comparable to the ramipril group.

Conclusion
Apigenin reduced renal damage due to diabetic nephropathy by suppressing oxidative stress, inflammation and fibrosis by inhibiting MAPK pathway.


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