Does Inhibition of Arginase and Advanced Glycation End Products Provide a Protection Against Experimentally Induced Diabetic Nephropathy?

Department of Physiology, Faculty of Medicine, Benha University, Egypt

Corresponding Author

Noha I. Hussien M.D.

Department of Physiology

Faculty of Medicine

Benha University

Egypt

Abstract

Diabetic nephropathy (DN) occurs in approximately one-third of all people with diabetes and is the leading cause of renal failure in developed and developing countries. The aim of the current study was to assess the possible protective effects of arginase and advanced glycation end (AGE) product inhibitors against DN and the possible underlying mechanisms. The present study was conducted on 40 male albino rats that were grouped into five groups of 8 rats each. Group I: control group that received single intraperitoneal (I.P.) injection of citrate Buffer. Group II: DN group that induced by administration of streptozotocin (STZ). Group III and Group IV have DN treated with L-citrulline an arginase inhibitor, and pyridoxamine (PM) an AGE inhibitor respectively. Group V: rats with DN treated with both L-citrulline and PM daily for 6 weeks. At the end of the treatment period blood glucose, urea, serum creatinine and urinary albumin excretion rate were measured. Renal tissue levels of AGEs, arginase activity, TGF-β1, malondialdehyde (MDA), reduced glutathione (GSH) and nitrate were assessed. DN group showed significant increase in albuminuria, blood glucose, urea, serum creatinine as well as renal AGEs, arginase activity, MDA and TGF-β1 concentrations, together with a significant decrease in renal NO and GSH. Administration of either L-citrulline or PM resulted in a significant amelioration of the above mentioned parameters. And their combination leads to more protective effect.  In conclusion, inhibition of both arginase and AGEs could represent therapeutic options for patients with DN.

Keywords: Diabetic Nephropathy; advanced glycation end product; arginase activity; L-citrulline; pyridoxamine.

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