title: Rosuvastatin attenuates contrast-induced nephropathy through modulation of nitric oxide, inflammatory responses, oxidative stress and apoptosis in diabetic male rats.
abstract: BACKGROUND
  Contrast-induced nephropathy (CIN) is an important cause of acute renal failure. We observe the effect of rosuvastatin on preventing CIN in diabetic rats in current study.
  
  
  METHODS
  Diabetic rats were then divided into five groups: 1 diabetic rats (D), 2 diabetic rats + contrast media (DCM), 3 diabetic rats + rosuvastatin (DR), 4 diabetic rats + contrast media + rosuvastatin (DRCM), 5 non-diabetic rat control (NDCM). Contrast-induced nephropathy was induced by intravenous injection a single dose of indomethacin (10 mg/kg), double doses of N-nitro-L-arginine methyl ester (10 mg/kg) and a single dose of high-osmolar contrast medium meglumine amidotrizoate (6 ml/kg). DR and DRCM group rats were treated with rosuvastatin (10 mg/kg/day) by gavage for 5 days. At the end of treatment, the experimental groups were sacrificed, and their renal tissues were investigated histopathologically beside assessments of functional activities, nitric oxide metabolites, and oxidative stress and apoptic markers.
  
  
  RESULTS
  After 6 days, serum creatinine and urine microprotein were increased, and creatinine clearance, kidney nitrite were decreased in DCM rats compared with NDCM, D, DR and DRCM groups. Histopathology scores in group DCM were increased compared with groups NDCM, D and DR, but lower in group DRCM than in group DCM (p < 0.01). Kidney thiobarbituric acid-reacting substances (TBARS), serum malondialdehyde (MDA), and serum protein carbonyl content (PCC) were increased, and serum thiol was decreased in the DCM group compared with groups NDCM, D and DR; however, these results were reversed in group DRCM compared with group DCM. Both expression of IL-6, TNF-α and the percentage of apoptotic cells were increased in group DCM than in groups NDCM, D and DR, but they were decreased in group DRCM than in group DCM. The expression of phospho-p38, cleaved capase-3, and the Bax/Bcl-2 ratio, were increased in group DCM than in groups NDCM, D and DR, but were decreased in group DRCM than in group DCM.
  
  
  CONCLUSIONS
  Our study demonstrated that rosuvastatin treatment attenuated both inflammatory processes and apoptosis and inhibited oxidative stress and the p38 MAPK pathway in a diabetic rat model in the setting of CIN.
authors.affiliation: Department of Cardiology, the General Hospital of Shenyang Military Region, Chinese People's Liberation Army, Shenyang, Liaoing, China. Jie.Deng@hotmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Cardiology, the General Hospital of Shenyang Military Region, Chinese People's Liberation Army, Shenyang, Liaoing, China. 565710586@qq.com.
authors.forename: Guijun
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Cardiology, the General Hospital of Shenyang Military Region, Chinese People's Liberation Army, Shenyang, Liaoing, China. 2822998560@qq.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Cardiology, the General Hospital of Shenyang Military Region, Chinese People's Liberation Army, Shenyang, Liaoing, China. 18640238150@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, the General Hospital of Shenyang Military Region, Chinese People's Liberation Army, Shenyang, Liaoing, China. shanxijqm@126.com.
authors.forename: Quanmin
authors.initials: Q
authors.lastname: Jing
authors.affiliation: Department of Cardiology, the General Hospital of Shenyang Military Region, Chinese People's Liberation Army, Shenyang, Liaoing, China. D.jie@126.com.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D003287:Contrast Media / Q000009:adverse effects*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium / Q000494:pharmacology / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; D000068718:Rosuvastatin Calcium; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3