Effects of sildenafil on oxidative and inflammatory injuries of the kidney in streptozotocin-induced diabetic rats.
BACKGROUND
Oxidative stress and inflammation are implicated in the pathogenesis of diabetic nephropathy. Because sildenafil citrate (Viagra) has variable cardiovascular benefits, including antioxidative and immunomodulating effects, we investigated its influence on oxidative stress and inflammation in diabetic rat kidney.


METHODS
Streptozotocin-induced diabetic rats received sildenafil (3 mg/kg/day in drinking water) or not (undosed water) for 8 weeks and were compared to age-matched nondiabetic animals. We evaluated 8-hydroxydeoxyguanosine (8-OHdG; for oxidative DNA damage), inducible nitric oxide synthase (iNOS) and nitrotyrosine (for excessive NO production and peroxynitrite formation), and representative chemoattractants [monocyte chemotactic protein-1, MCP-1; for inflammation and monocyte/macrophage infiltrations (ED-1)] in the kidney.


RESULTS
Sildenafil-treated rats had a lower kidney-to-body weight ratio than untreated diabetic rats. Urinary albumin excretion in diabetic rats decreased significantly after sildenafil treatment without changes in systolic blood pressure. Sildenafil-treated rats had significantly lower urinary and renal cortical 8-OHdG levels than the nonsildenafil group. Sildenafil administration significantly attenuated the increased renal nitrotyrosine protein expression, positive iNOS and ED-1 staining in glomeruli and tubulointerstitium, and nitrotyrosine staining in tubulointerstitium. Cortical MCP-1 RNA expression in the sildenafil group was significantly lower than in the nonsildenafil group.


CONCLUSIONS
Sildenafil treatment may attenuate renal damage by ameliorating oxidative and inflammatory injuries in diabetic rats.
Jeong
Kyung-Hwan
KH
Department of Nephrology, School of Medicine, Kyung Hee University, Seoul, Korea.
Lee
Tae-Won
TW
Ihm
Chun-Gyoo
CG
Lee
Sang-Ho
SH
Moon
Ju-Young
JY
Lim
Sung-Jig
SJ
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D009393:Nephritis / Q000378:metabolism / Q000517:prevention & control; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013311:Streptozocin; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000097382:CD68 Molecule
D000080242:8-Hydroxy-2'-Deoxyguanosine; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D018932:Chemokine CCL2; D003849:Deoxyguanosine; D018836:Inflammation Mediators; D052247:Nitric Oxide Synthase Type II; D010879:Piperazines; D011687:Purines; D012333:RNA, Messenger; D000068677:Sildenafil Citrate; D013311:Streptozocin; D013450:Sulfones; D014443:Tyrosine; D014665:Vasodilator Agents; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C491766:Ccl2 protein, rat; C002744:3-nitrotyrosine; C496318:Nos2 protein, rat