Atorvastatin ameliorates tissue damage of obstructed ureter in rats

Chuang, Yen-Hwang; Chuang, Wan–Long; Huang, Shu‐Pin; Liu, Ching-Kuan; Huang, Chun‐Hsiung

doi:10.1016/j.lfs.2011.09.010

Cited by 6 publications

(7 citation statements)

References 40 publications

(99 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings suggest that atorvastatin improves renal inflammation by attenuating the activation of the NF-κB pathway. This is in agreement with the anti-inflammatory effects of atorvastatin found in heart failure [ 43 ], obstructive uropathy [ 44 ] and endotoxemia [ 45 ]. Additionally, previous studies demonstrated that gentamicin increased macrophage infiltration and elevated TGFβ1 level leading to the progression of tubulointerstitial nephritis [ 26 , 46 ].…”

Section: Discussionsupporting

confidence: 90%

“…Additionally, previous studies demonstrated that gentamicin increased macrophage infiltration and elevated TGFβ1 level leading to the progression of tubulointerstitial nephritis [ 26 , 46 ]. An expression of TGFβ1 showed a strong correlation with fibrosis of smooth muscle layer in rats with unilateral ureteral obstruction [ 44 ]. In animal models with ureter obstruction, statins have been reported to inhibit inflammatory mediators and macrophage infiltration [ 47 ], and to suppress TGFβ1 expression and extracellular matrix production [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity

et al. 2016

View full text Add to dashboard Cite

Gentamicin is a commonly used aminoglycoside antibiotic. However, its therapeutic use is limited by its nephrotoxicity. The mechanisms of gentamicin-induced nephrotoxicity are principally from renal inflammation and oxidative stress. Since atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, exerts lipid-lowering effects, antioxidant, anti-inflammatory as well as anti-apoptotic effects, this study aimed to investigate the protective effects of atorvastatin against gentamicin-induced nephrotoxicity. Male Sprague Dawley rats were used and nephrotoxicity was induced by intraperitoneal injection of gentamicin, 100 mg/kg/day, for 15 days. Atorvastatin, 10 mg/kg/day, was administered by orally gavage 30 min before gentamicin injection on day 1 to 15 (pretreatment) or on day 10 to15 (delayed treatment). For only atorvastatin treatment group, it was given on day 1 to 15. At the end of the experiment, kidney weight, blood urea nitrogen and serum creatinine as well as renal inflammation (NF-κB, TNFαR1, IL-6 and iNOS), renal fibrosis (TGFβ1), ER stress (calpain, GRP78, CHOP, and caspase 12) and apoptotic markers (cleaved caspase-3, Bax, and Bcl-2) as well as TUNEL assay were determined. Gentamicin-induced nephrotoxicity was confirmed by marked elevations in serum urea and creatinine, kidney hypertrophy, renal inflammation, fibrosis, ER stress and apoptosis and attenuation of creatinine clearance. Atorvastatin pre and delayed treatment significantly improved renal function and decreased renal NF-κB, TNFαR1, IL-6, iNOS and TGFβ1 expressions. They also attenuated calpain, GRP78, CHOP, caspase 12, Bax, and increased Bcl-2 expressions in gentamicin-treated rat. These results indicate that atorvastatin treatment could attenuate gentamicin-induced nephrotoxicity in rats, substantiated by the reduction of inflammation, ER stress and apoptosis. The effect of atorvastatin in protecting from renal damage induced by gentamicin seems to be more effective when it beginning given along with gentamicin or pretreatment.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The current study indicates that statins are able to significantly inhibit myocardial apoptosis, thus protecting the heart function. Statins may play important roles in the inhibition of apoptosis by various mechanisms (22). …”

Section: Discussionmentioning

confidence: 99%

“…Atorvastatin (AVT), as a statin, has been reported to dose-dependently reduce the expression of numerous inflammatory cytokines, attenuate the reduction of PPAR expression levels, inhibit cardiomyocyte hypertrophy and improve the ventricular diastolic function in aged hypertensive patients (22–25). Although there have been several studies on the cardiovascular protective effects of statins, the roles and mechanisms of statin intervention in the occurrence and development processes of cardiac aging have been incompletely investigated.…”

Section: Introductionmentioning

confidence: 99%

Effects of long-term atorvastatin treatment on cardiac aging

Han

Liu

2013

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

A number of studies have reported that atorvastatin (AVT) may have an important role in the delay of cardiac aging. However, the mechanism by which AVT affects cardiac aging has not been established. In this study, a series of experiments were performed to investigate the effects of AVT treatment on the cardiovascular system and the associated mechanism. Wistar rats were administered AVT or saline for 4 months. Age-related changes in the hearts were measured at the end of the experiment. The results showed that compared with young rats, the aged rats had significant changes indicative of myocardial aging, including increased blood lipid 1evelss, increased body weight, cardiac hypertrophy, larger myocardial cells, irregular muscle fibers, fewer deeply stained nuclei, smaller intercellular spaces, a larger number of apoptotic cells and increased levels of lipofuscin in myocardial tissue. However, long-term AVT treatment was able to significantly delay or even reverse these aging-related changes. In addition, these effects showed a certain dose-dependence. In general, long-term AVT treatment reduces blood lipids, inhibits cardiac hypertrophy, suppresses cardiomyocyte apoptosis and lowers the level of oxidative stress to protect the heart from aging.

show abstract

“…In this regard, the administration of atorvastatin ameliorated the tissue damaged of obstructed ureters in an experimental model [66]. The expression of TGF- β 1 and of the proinflammatory cytokines IL-1 β , IL-6, and TNF- α was decreased following atorvastain treatment [66]. Another rational approach to blunt renal fibrosis is to block growth factors effects.…”

Section: Cytokines In Cakut: Experimental Studiesmentioning

confidence: 99%

Interactions between Cytokines, Congenital Anomalies of Kidney and Urinary Tract and Chronic Kidney Disease

Silva

Valerio

Vasconcelos

et al. 2013

Clinical and Developmental Immunology

View full text Add to dashboard Cite

Fetal hydronephrosis is the most common anomaly detected on antenatal ultrasound, affecting 1–5% of pregnancies. Postnatal investigation has the major aim in detecting infants with severe urinary tract obstruction and clinically significant urinary tract anomalies among the heterogeneous universe of patients. Congenital uropathies are frequent causes of pediatric chronic kidney disease (CKD). Imaging techniques clearly contribute to this purpose; however, sometimes, these exams are invasive, very expensive, and not sufficient to precisely define the best approach as well as the prognosis. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric urological diseases. In this regard, recent studies suggest a role for cytokines and chemokines in the pathophysiology of CAKUT and for the progression to CKD. Some authors proposed that the evaluation of these inflammatory mediators might help the management of postnatal uropathies and the detection of patients with high risk to developed chronic kidney disease. Therefore, the aim of this paper is to revise general aspects of cytokines and the link between cytokines, CAKUT, and CKD by including experimental and clinical evidence.

show abstract

Atorvastatin ameliorates tissue damage of obstructed ureter in rats

Cited by 6 publications

References 40 publications

Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity

Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity

Effects of long-term atorvastatin treatment on cardiac aging

Interactions between Cytokines, Congenital Anomalies of Kidney and Urinary Tract and Chronic Kidney Disease

Contact Info

Product

Resources

About