Rosuvastatin attenuates contrast-induced nephropathy through modulation of nitric oxide, inflammatory responses, oxidative stress and apoptosis in diabetic male rats

Abstract

BackgroundContrast-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.MethodsDiabetic 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.ResultsAfter 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.ConclusionsOur 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.

Synergistic effects of the capsaicinoid nonivamide and rosuvastatin on obesity‐related endothelial dysfunction in rat fed a high‐fat diet

“…RSV (3‐hydroxy‐3‐methylglutaryl coenzyme‐A [HMG‐CoA] reductase inhibitor) is a widely used contemporary statin. Many studies have shown that RSV has pleiotropic anti‐inflammatory and antioxidant effects and that it also improves endothelial function (Deng et al, ; Nade et al, ; Schäfer et al, ; Suh et al, ). However, other studies have reported that statins can promote fat deposition in the liver and that there are reverse effects after withdrawal from high doses of statins (Pantan et al, ).…”

“…The activation of TRPV1 by PAVA has been reported to be associated with anti‐inflammatory, antioxidant, and anti‐obesity effects (Srinivasan, ; Morales‐Martínez et al, ; Hochkogler et al, ). RSV has been shown to have anti‐inflammatory and antioxidant effects and to improve endothelial function (Deng et al, ; Nade et al, ; Schäfer et al, ; Suh et al, ). Our study showed the treatments of PAVA and RSV yielded similar results.…”

“…Rosuvastatin (RSV; 3‐hydroxy‐3‐methylglutaryl coenzyme‐A [HMG‐CoA] reductase inhibitor) is a third‐generation statin. RSV has been shown to have pleiotropic anti‐inflammatory and antioxidant properties; in addition, it can improve endothelial function (Deng et al, ; Nade, Kawale, & Patel, ; Schäfer et al, ; Suh et al, ). In contrast, a previous study reported adverse effects of high doses of statin in the form of reverse effects after withdrawal (Pantan, Tocharus, Suksamrarn, & Tocharus, ).…”

The glucagon‐like peptide‐1 receptor agonist Exendin‐4, ameliorates contrast‐induced nephropathy through suppression of oxidative stress, vascular dysfunction and apoptosis independent of glycaemia

“…This increases the concentration and viscosity of the tubular fluid, which subsequently increases the tubular hydrostatic pressure. As a result, the renal perfusion pressure and renal blood flux are diminished to eventually induce medullary hypoxia . Both impaired renal perfusion and hypoxia can increase oxidative stress, conceivably by triggering an excessive generation of ROS .…”

Pueraria tuberosa extract inhibits iNOS and IL-6 through suppression of PKC-α and NF-kB pathway in diabetes-induced nephropathy

“…It has multi‐aetiological pathogenesis such as oxidative stress, inflammation, production of advanced glycation end products (AGEs) and PKC activation, which are attributed to hyperglycaemia, hyperlipidaemia and hypertensive state . Previous reports from DN patient and animal model have indicated that inflammation plays a significant role in the development and progression of DN . Activation of PKC is considered as an important signalling molecule in progression of DN as it attributed to an abnormality in vascular and cellular processes causing vascular permeability, endothelial dysfunction, angiogenesis, ECM accumulation, basement thickening and alteration in various enzymatic activity and transcription factors .…”