Effect of unilateral ureteral obstruction and anti-angiotensin II treatment on renal tubule cell apoptosis and interstitial fibrosis in rats

Scientific paper - Original scientific paper

• Title (croatian): Učinak jednostrane opstrukcije uretera i primjene anti-angiotenzina II apoptozu i intersticijalnu fibrozu bubrežnih tubularnih stanica u štakore
• Author: Nikola Radović
• Author: Gorana Aralica
• Author: Danica Galešić Ljubanović
• Author: Vjekoslav Jeleč
• Author: Mladen Kontek
• Author's institution: University of Zagreb; School of Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences

Abstract (english)

Unilateral ureteral obstruction (UUO) results in a number of pathophysiological and morphological changes in the renal parenchyma, including interstitial inflammation and fibrosis, apoptotic changes of tubular and interstitial cells. Recent studies have indicated an association between renin-angiotensin system and apoptotic alterations in the kidney after unilateral obstructive nephropathy. In this study, the effect of ACE inhibitors and AT1 receptor antagonists on tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy after UUO in rats was investigated. The study was conducted on Wistar rats with unilaterally ligated ureter and sham operated animals (control group). The rats with UUO were treated with ACE inhibitor (cilazapril) or AT1 receptor antagonists (losartan) and control group was treated with H2O. Sham-operated animals were treated in the same way. Tubular and interstitial cell apoptosis was detected morphologically by hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL). The area of intersitial fibrosis was determined using computer-assisted image processing after Gomory silver impregnation of paraffin sections. All experimental animal groups with unilateral ureter ligation showed a significantly increased number of apoptotic tubular and interstitial cells in the obstructed kidney compared with the contralateral, unobstructed kidney. Histomorphometric analysis of renal interstitial fibrotic changes in the groups of rats treated with losartan or water showed a statistically significant difference (p < 0.05) between the operated and sham--operated animals. In conclusion, following UUO there is a significantly increased number of apoptotic tubular cells and interstitial fibrosis in the ipsilateral kidney compared with the contralateral kidney. ACE inhibitors and AT1 receptor antagonists could not decrease the extent of renal cells apoptosis and interstitial fibrosis after UUO.

Abstract (croatian)

Rezultat jednostrane opstrukcije uretera (JOU) je gubitak parenhima u bubregu zbog atrofije kanalića, upalnih i
fibroznih promjena u intersticiju i apoptoze stanica bubrežnih kanalića i intersticija. Dokazana je povezanost sustava
renin-angiotenzin i apoptotskih promjena u bubregu nakon jednostrane opstrukcijske nefropatije. U ovoj studiji je
istraživan učinak inhibitora ACE i antagonista receptora AT1 na apoptozu stanica tubula i na intersticijsku fibrozu kod
opstrukcijske nefropatije nakon JOU u štakora. Istraživanje je provedeno na štakorima soja Wistar kojima je jednostrano
podvezan ureter ili su bili lažno operirani (kontrola). Životinje s podvezanim ureterom obrađene su inhibitorima
ACE (cilazapril) ili antagonistima receptora AT1 (lozartan), a kontrolna skupina životinja obrađena je s H2O. Lažno
operirane životinje obrađene su na isti način. Apoptoza stanica u kanalićima i intersticiju je morfološki analizirana
nakon bojenja hemalaun eozinom (HE) i bojanjem terminalne deoksinukleotidil transferaze na 3, – OH krajevima DNA
(TUNEL). Površinu intersticijske fibroze na parafinskim prerezima odredili smo pomoću računalne obrade slike nakon
impregnacije uzoraka srebrom po Gomoriu. U svim eksperimentalnim skupinama životinja s podvezanim ureterom
značajno je povećan broj apoptotskih stanica u kanalićima bubrega u odnosu na suprotni, neopstruirani bubreg. Histomorfometrijska
analiza fibroznih promjena intersticija bubrega u skupinama životinja obrađenih lozartanom ili vodom,
pokazala je statistički značajnu razliku (p<0,05) između operiranih i lažno operiranih životinja. Nakon podvezanja
jednog uretera dolazi do značajno povećanog broja apoptotskih stanica u kanalićima te fibroze istostranog bubrega u
odnosu na suprotni bubreg. Inhibitori ACE i antagonisti receptora AT1 ne mogu smanjiti oštećenja stanica bubrega
koja su nastala u tijeku JOU.

• Keywords (english): Angiotensin II/drug effects; Animals; Apoptosis; In Situ Nick-End Labeling; Kidney Tubules/pathology; Male; Rats; Rats, Wistar; Ureteral Obstruction/drug therapy
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Collegium Antropologicum
• Numbering: vol. 38, no. 2, pp. 583-588
• p-ISSN: 0350-6134
• URN:NBN: urn:nbn:hr:105:108834
• Publication: 2014-06
• Document URL: https://hrcak.srce.hr/127565
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-03-28 08:19:04