The effect of nitro-oleic versus losartan in diabetic nephropathy: modulation of parathyroid hormone-related protein

Background: Parathyroid hormone-related protein (PTHrP) involvement in the mechanisms related to angiotensin II (AngII)-induced renal injury has become an emerging concern. The current study was thus designed to compare the possible preventive and therapeutic effect of AngII antagonists, losartan and nitro-oleic (NO2-OA) acid, on diabetic nephropathy (DN) and evaluate their effect on PTHrP modulation as well as on the functional and histopathological parameters in the kidney of diabetic rats.  Materials and methods: Forty eight adult male Sprague Dawley rats were divided into control group, DN group, pre-diabetic nephropathy (pre-DN) losartan group, pre-diabetic nephropathy nitro-oleic acid (pre-DN NO2-OA) group, post-diabetic nephropathy (post-DN) losartan and post-diabetic nephropathy nitro-oleic acid (post-DN NO2-OA) groups. At the end of the study, systolic blood pressure (SBP), serum fasting glucose, glomerular filtration rate (GFR), urea, urea albumin excretion (UAE), serum angiotensin, renal PTHrP gene expression and correlations between PTHrP and SBP, serum glucose, AngII and kidney functions were evaluated. Histo- logical examination, Masson’s trichrome, periodic acid-Schiff staining as well as morphometric analysis and histopathological scoring for tubular and glomerular parameters have been carried out.  Results: Prophylactic losartan and NO2-OA were associated with improvement in SBP, serum glucose, urea, GFR, UAE, with reduction in serum AngII and PTHrP overexpression observed in diabetic kidney. Treatment with losartan and NO2-OA showed the same effect except that post-DN NO2-OA showed no significant effect regarding kidney function. Strong correlations were observed between PTHrP and SBP, serum glucose, AngII and kidney functions. Histopathological results revealed obvious improvement in glomerulosclerosis, vascular and tubular injury parameters in prophylactic groups especially with losartan.  Conclusions: Both pre and post-DN losartan, NO2-OA may have a potential role in protection and regression of DN through reduction of PTHrP overexpression.