Purpose: The current study was done to determine whether atorvastatin, the HMGCoA (3-hydroxy-3-methylglutaryl CoA) reductase inhibitor, could decrease renal transforming growth factor-beta (TGF-beta) levels in unilateral ureteral obstruction (UUO) and concomitantly affect renal tissue damage in UUO.
Materials And Methods: Atorvastatin (20 mg/kg) was administered to rats 1 day prior to UUO and every day thereafter. Kidneys were harvested at day 14 after UUO. Tissue TGF-beta was measured by bioassay using mink lung epithelial cells. Renal tubular proliferation and apoptosis were detected by immunostaining proliferating cell nuclear antigen and polyclonal antisingle strand DNA antibody, respectively. Fibrosis was assessed by measuring collagen deposition with trichrome stained slides. Interstitial leukocyte was detected by immunostaining CD45.
Results: TGF-beta bioassay showed that the obstructed kidney in the control group contained significantly higher TGF-beta than the unobstructed kidney in the control group (mean +/- SD 79.1 +/- 48.5 vs 28.7 +/- 13.7 pg/mg tissue) and atorvastatin significantly decrease tissue TGF-beta in the obstructed kidney (53.4 +/- 37.0 pg/mg tissue). Immunostaining polyclonal antisingle strand DNA antibody demonstrated that the obstructed kidney in the control group has significantly more tubular apoptosis than the unobstructed counterpart (4.8 +/- 2.8 vs 2.1 +/- 1.2 nuclei per high power field) and atorvastatin significantly decreased renal tubular apoptosis in the obstructed kidney (1.1 +/- 0.7 nuclei per high power field). In addition, immunostaining proliferating cell nuclear antigen showed that the obstructed kidney in the atorvastatin group had significantly more renal tubular proliferation than the obstructed kidney in the control group (48.7 +/- 20.8 vs 17.3 +/- 10.6 per high power field). Control obstructed kidney showed significantly more fibrosis, which was also blunted by atorvastatin.
Conclusions: Atorvastatin significantly decreases tissue TGF-beta, resulting in a decrease in tubular damage and interstitial fibrosis. This suggests that atorvastatin is a promising agent for preventing renal tubular damage in UUO.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/01.ju.0000138473.38447.f0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Macedo ileum-based reservoir for the management of bladder involvement in epidermolysis bullosa.
J Pediatr Urol
December 2024
Department of Pediatric Surgery and Urology, Medical University of Silesia, ul. Medyków 16, 40-752, Katowice, Poland.
Introduction: Epidermolysis bullosa (EB) can severely affect the urinary tract, leading to strictures and urine outflow obstruction, which pose significant risks to kidney function. Procedures involving the urinary mucosa often exacerbate these issues, making safe bladder emptying a major challenge. This study reviews surgical methods for managing urological complications in EB patients, with a focus on the Macedo procedure, which offers a promising alternative that avoids further bladder mucosa irritation and prevents disease exacerbation.
View Article and Find Full Text PDFPrenatal intervention for a large ureterocele in a male fetus causing lower urinary tract obstruction "Society of Fetal Urology Case Reports, Fall 2024".
Urology
January 2025
Department of Maternal Fetal Medicine, Ontario Fetal Center, Mount Sinai Hospital, Toronto, Ontario, Canada.
A male fetus at 20 weeks of gestation presented with severe bilateral hydroureteronephrosis and distended bladder due to a large ureterocele. A percutaneous ureterocele puncture at 21+3 weeks aimed to decompress the ureterocele, unclog the lower urinary tract, and prevent renal damage. Post-puncture, the ureterocele decompressed, with improved left hydronephrosis and a normal right kidney.
View Article and Find Full Text PDFUbiquitin-specific peptidase 10 promotes renal interstitial fibrosis progression through deubiquitinating and stabilizing P53 protein.
Biochim Biophys Acta Mol Basis Dis
January 2025
Department of Pediatric Nephrology and Rheumatism and Immunology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Department of Pediatric Nephrology and Rheumatism and Immunology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China. Electronic address:
Renal interstitial fibrosis is the main factor determining chronic kidney disease (CKD) progression, and renal tubular epithelial cells are the key drivers of this pathological process. Herein, we revealed significantly increased ubiquitin-specific peptidase 10 (USP10) expression in the kidney tissues of both patients with CKD and mice induced by unilateral ureteral obstruction, as well as in transforming growth factor-beta 1 (TGFβ1)-induced renal tubular epithelial cells. In vivo, treatment with the USP10 small molecule inhibitor Spautin-1, which inhibits its deubiquitinating activity, weakened renal interstitial fibrosis progression and alleviated the subsequent inflammatory response and oxidative stress in male mice.
View Article and Find Full Text PDFBackground: Timely identification of mild cognitive impairment (MCI) is key to early intervention. While primary care providers are the most likely entry point to detect early signs of MCI, their detection rates are low. Building upon a published study, we used electronic health records (EHR) to develop a clinically enhanced MCI risk prediction algorithm.
View Article and Find Full Text PDFA novel suture-free nephroplication with 4D-printed biodegradable bag for giant hydronephrosis: initial experience from hydromechanics and clinical application.
Int J Surg
January 2025
Department of Urology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
Background: Giant hydronephrosis as an rare condition is often caused by chronic ureteral obstruction. Nephroplication is a crucial procedure to improve urinary drainage in the kidney-sparing surgery for patients with giant hydronephrosis. However, traditional nephroplication via suturing kidney has technical difficulty and many potential risks.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!