title: Effect of PACAP treatment on kidney morphology and cytokine expression in rat diabetic nephropathy.
abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide, exerting diverse effects. One of its frequently examined functions is cell protection, which is achieved mainly via inhibiting apoptotic, inflammatory and oxidative processes. All its three receptors (PAC1, VPAC1, VPAC2) are expressed in the kidney and PACAP has been shown to have protective effects against different renal pathologies. Diabetic nephropathy is the leading cause of end stage renal disease. The aim of the present study was to investigate the possible ameliorative effect of PACAP in streptozotocin-induced diabetic nephropathy and to evaluate its anti-inflammatory effect in this model. Diabetes was induced by a single intravenous injection of streptozotocin (65 mg/kg) in male Wistar rats. PACAP-treated animals were administered ip. 20 μg PACAP every second day, while untreated animals were given vehicle. Kidneys were removed after 8-weeks survival. Besides the complex histological analysis (glomerular PAS positive area/glomerulus area, tubular damage, arteriolar hyalinosis), expression of several cytokines was evaluated by cytokine array and Luminex assay. Histological analysis revealed severe diabetic changes in kidneys of control diabetic animals (glomerular PAS-positive area expansion, tubular damage, Armanni-Ebstein phenomenon). PACAP treatment significantly diminished the damage. Diabetic kidneys showed significant cytokine activation compared to their healthy controls. PACAP was effective in downregulation of several cytokines including CINC-1, TIMP-1, LIX, MIG, s-ICAM. To conclude, PACAP is effective in ameliorating diabetic nephropathy at least partly through its well-known anti-inflammatory effect. These results raise the opportunity for the use of PACAP as a possible therapeutic or preventive method in treating the complications of diabetes.
authors: Department of Anatomy PTE-MTA Lendulet PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: E
authors: E
authors: Banki
authors: P
authors: P
authors: Degrell
authors: P
authors: P
authors: Kiss
authors: K
authors: K
authors: Kovacs
authors: A
authors: A
authors: Kemeny
authors: K
authors: K
authors: Csanaky
authors: A
authors: A
authors: Duh
authors: D
authors: D
authors: Nagy
authors: G
authors: G
authors: Toth
authors: A
authors: A
authors: Tamas
authors: D
authors: D
authors: Reglodi
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D054360:Chemokine CXCL1 / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D017208:Rats, Wistar; D013311:Streptozocin; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; C505723:CXCL9 protein, rat; D054360:Chemokine CXCL1; D054370:Chemokine CXCL9; C513297:Cxcl1 protein, rat; D016207:Cytokines; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D013311:Streptozocin