scholarly journals Unilateral Ureteral Obstruction as a Model of Kidney Fibrosis and Increasing of Systolic Blood Pressure in Mice

2019 ◽  
Vol 2 (3) ◽  
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Systolic Blood Pressure ◽  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Tubulointerstitial Fibrosis ◽  
Obstructive Nephropathy ◽  
Kidney Fibrosis ◽  
End Stage

Background: Obstructive nephropathy can lead to progressive and permanent loss of kidney function characterized by interstitial inflammation and tubulointerstitial fibrosis. Tubulointerstitial fibrosis presents as the end result of various kidney injuries in general and can cause chronic kidney disease (CKD), which can progress to end-stage kidney disease and hypertension. Objective: This study aimed to determine the effectiveness of unilateral ureteral obstruction (UUO) as a model of renal fibrosis and hypertension. Method: Sixteen male Rattus norvegicus mice (150-200 g) were divided into control groups and UUO by ureteral ligation, eight mice each. The systolic blood pressure (SBP) were measured every seven days. After 30 days the animals were dissected to analyze the changes in renal interstitial fibrosis. Statistical analysis was carried out by unpaired t test or alternative test. Results: There was a significant increase in interstitial fibrosis in the UUO rat group [1% (0% - 5%) vs. 75% (20% - ­90%), p <0.001] and SBP [85.38 ± 1.69 mmHg vs 144.75 ± 4.27 mmHg, p <0.001]. Conclusion: UUO can be used as a model of fibrosis and hypertension, which can be used as the basis for the development of anti-fibrotic and anti-hypertensive drugs.

scholarly journals NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Honglei Guo ◽  
Xiao Bi ◽  
Ping Zhou ◽  
Shijian Zhu ◽  
Wei Ding
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mitochondrial Dysfunction ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Tubulointerstitial Fibrosis ◽  
Mitochondrial Morphology ◽  
Glomerular Injury ◽  
Matrix Deposition

Background and Aims. The nucleotide-binding domain and leucine-rich repeat containing PYD-3 (NLRP3) inflammasome has been implicated in the pathogenesis of chronic kidney disease (CKD); however, its exact role in glomerular injury and tubulointerstitial fibrosis is still undefined. The present study was performed to identify the function of NLRP3 in modulating renal injury and fibrosis and the potential involvement of mitochondrial dysfunction in the murine unilateral ureteral obstruction (UUO) model of CKD. Methods. Employing wild-type (WT) and NLRP3−/− mice with or without UUO, we evaluated renal structure, tissue injury, and mitochondrial ultrastructure, as well as expression of some vital molecules involved in the progression of fibrosis, apoptosis, inflammation, and mitochondrial dysfunction. Results. The severe glomerular injury and tubulointerstitial fibrosis induced in WT mice by UUO was markedly attenuated in NLRP3−/− mice as evidenced by blockade of extracellular matrix deposition, decreased cell apoptosis, and phenotypic alterations. Moreover, NLRP3 deletion reversed UUO-induced impairment of mitochondrial morphology and function. Conclusions. NLRP3 deletion ameliorates mitochondrial dysfunction and alleviates renal fibrosis in a murine UUO model of CKD.

scholarly journals Dicer deficiency in proximal tubules exacerbates renal injury and tubulointerstitial fibrosis and upregulates Smad2/3

2018 ◽  
Vol 315 (6) ◽  
pp. F1822-F1832 ◽  
Author(s):  
Zhengwei Ma ◽  
Qingqing Wei ◽  
Ming Zhang ◽  
Jian-Kang Chen ◽  
Zheng Dong
Keyword(s):  
Kidney Disease ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Proximal Tubules ◽  
Tubulointerstitial Fibrosis ◽  
Obstructive Nephropathy ◽  
Pathological Feature ◽  
Tubular Injury

Renal fibrosis is a common pathological feature in chronic kidney disease (CKD), including diabetic kidney disease (DKD) and obstructive nephropathy. Multiple microRNAs have been implicated in the pathogenesis of both DKD and obstructive nephropathy, although the overall role of microRNAs in tubular injury and renal fibrosis in CKD is unclear. Dicer (a key RNase III enzyme for microRNA biogenesis) was specifically ablated from kidney proximal tubules in mice via the Cre-lox system to deplete micoRNAs. Proximal tubular Dicer knockout (PT- Dicer KO) mice and wild-type (WT) littermates were subjected to streptozotocin (STZ) treatment to induce DKD or unilateral ureteral obstruction (UUO) to induce obstructive nephropathy. Renal hypertrophy, renal tubular apoptosis, kidney inflammation, and tubulointerstitial fibrosis were examined. Compared with WT mice, PT- Dicer KO mice showed more severe tubular injury and renal inflammation following STZ treatment. These mice also developed higher levels of tubolointerstitial fibrosis. Meanwhile, PT- Dicer KO mice had a significantly higher Smad2/3 expression in kidneys than WT mice (at 6 mo of age) in both control and STZ-treated mice. Similarly, UUO induced more severe renal injury, inflammation, and interstitial fibrosis in PT- Dicer KO mice than WT. Although we did not detect obvious Smad2/3 expression in sham-operated mice (2–3 mo old), significantly more Smad2/3 was induced in obstructed PT- Dicer KO kidneys. These results supported a protective role of Dicer-dependent microRNA synthesis in renal injury and fibrosis development in CKD, specifically in DKD and obstructive nephropathy. Depletion of Dicer and microRNAs may upregulate Smad2/3-related signaling pathway to enhance the progression of CKD.

scholarly journals SREBP inhibition ameliorates renal injury after unilateral ureteral obstruction

2016 ◽  
Vol 311 (3) ◽  
pp. F614-F625 ◽  
Author(s):  
Maria Mustafa ◽  
Tony N. Wang ◽  
Xing Chen ◽  
Bo Gao ◽  
Joan C. Krepinsky
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Ureteral Obstruction ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Fibrotic Process ◽  
Atubular Glomeruli ◽  
Tgf Β1

Tubulointerstitial fibrosis is a major feature associated with declining kidney function in chronic kidney disease of diverse etiology. No effective means as yet exists to prevent the progression of fibrosis. We have shown that the transcription factor sterol-regulatory element-binding protein 1 (SREBP-1) is an important mediator of the profibrotic response to transforming growth factor-β (TGF-β) and angiotensin II, both key cytokines in the fibrotic process. Here, we examined the role of SREBP in renal interstitial fibrosis in the unilateral ureteral obstruction (UUO) model. The two isoforms of SREBP (-1 and -2) were activated by 3 days after UUO, with SREBP-1 showing a more sustained activation to 21 days. We then examined whether SREBP1/2 inhibition with the small-molecule inhibitor fatostatin could attenuate fibrosis after 14 days of UUO. SREBP activation was confirmed to be inhibited by fatostatin. Treatment decreased interstitial fibrosis, TGF-β signaling, and upregulation of α-smooth muscle actin (SMA), a marker of fibroblast activation. Fatostatin also attenuated inflammatory cell infiltrate and apoptosis. Associated with this, fatostatin preserved proximal tubular mass. The significant increase in atubular glomeruli observed after UUO, known to correlate with irreversible renal functional decline, was also decreased by treatment. In cultured primary fibroblasts, TGF-β1 induced the activation of SREBP-1 and -2. Fatostatin blocked TGF-β1-induced α-SMA and matrix protein upregulation. The inhibition of SREBP is thus a potential novel therapeutic target in the treatment of fibrosis in chronic kidney disease.

Protective effects of low-dose carbon monoxide against renal fibrosis induced by unilateral ureteral obstruction

2008 ◽  
Vol 294 (3) ◽  
pp. F508-F517 ◽  
Author(s):  
Lin Wang ◽  
Ji-Yang Sophie Lee ◽  
Joon Hyeok Kwak ◽  
Yanjuan He ◽  
Sung Il Kim ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Low Dose ◽  
Tissue Injury ◽  
Unilateral Ureteral Obstruction ◽  
Tubulointerstitial Fibrosis ◽  
In Vivo Model ◽  
Obstructive Nephropathy ◽  
Protective Effects

Tubulointerstitial fibrosis is a hallmark of chronic progressive kidney disease leading to end-stage renal failure. An endogenous product of heme oxygenase activity, carbon monoxide (CO), has been shown to exert cytoprotection against tissue injury. Here, we explored the effects of exogenous administration of low-dose CO in an in vivo model of renal fibrosis induced by unilateral ureteral obstruction (UUO) and examined whether CO can protect against kidney injury. UUO in mice leads to increased extracellular matrix (ECM) deposition and tubulointerstitial fibrosis within 4 to 7 days. Kidneys of mice exposed to low-dose CO, however, had markedly reduced ECM deposition after UUO. Moreover, low-dose CO treatment inhibited the induction of α-smooth muscle actin (α-SMA) and major ECM proteins, type 1 collagen and fibronectin, in kidneys after UUO. In contrast, these anti-fibrotic effects of CO treatment were abrogated in mice carrying null mutation of Mkk3, suggesting involvement of the MKK3 signaling pathway in mediating the CO effects. Additionally, in vitro CO exposure markedly inhibited TGF-β1-induced expression of α-SMA, collagen, and fibronectin in renal proximal tubular epithelial cells. Our findings suggest that low-dose CO exerts protective effects, via the MKK3 pathway, to inhibit development of renal fibrosis in obstructive nephropathy.

scholarly journals Centella asiatica Extract Attenuates Kidney Fibrosis Through Reducing Mesenchymal Transition and Inflammation in Ureteral Ligation Model in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Dwi Cahyani Ratna Sari ◽  
Santosa Budiharjo ◽  
Husnari Afifah ◽  
Destantry Jasmin ◽  
Orisativa Kokasih ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Area Fraction ◽  
Sham Operation ◽  
Tubular Injury ◽  
Kidney Fibrosis ◽  
Mesenchymal Transition ◽  
E Cadherin

Background: Kidney fibrosis is the common final pathway of chronic kidney disease (CKD), and is characterized by inflammation, mesenchymal transition with myofibroblast formation and epithelial to mesenchymal transition (EMT). Centella asiatia (CeA) is an herb that has a reno-protective effect. However, its mechanism of action in kidney fibrosis has not been elucidated.Aim: To elucidate the effect of CeA in amelioration of kidney fibrosis in a unilateral ureteral obstruction (UUO) model and focus on mesenchymal transition and inflammation.Methods: Unilateral ureteral obstruction was performed in male Swiss-background mice (age: 2–3 months, weight: 30–40 g, UUO group n = 6) to induce kidney fibrosis. Two doses of CeA extract with oral administration, 210 and 840 mg/kg body weight were added in UUO (U+C210 and U+C840 groups, each n = 6). The sham operation procedure was performed for the control group (SO, n = 6). The mice were euthanized at day-14 after operation. Tubular injury and interstitial fibrosis area fractions in kidney tissues of the mice were quantified based on periodic acid-Schiff (PAS) and Sirius Red (SR) staining. Immunostaining was performed for examination of fibroblast (PDGFR-β), myofibroblast (α-SMA), Monocyte Chemoattractant Protein-1 (MCP-1) and macrophage (CD68), meanwhile double immunofluorescence was performed with PDGFR-β and α-SMA. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to examine mRNA expression of TGF-β, Collagen-1, Snail, E-cadherin, vimentin, fibroblast-specific protein 1 (FSP-1), CD68, toll-like receptor 4 (TLR4), and MCP-1.Results: We observed a significantly higher interstitial fibrosis area fraction and tubular injury (p &lt; 0.001) with fibroblast expansion and myofibroblast formation in the UUO group than in the SO group. These findings were associated with higher mRNA expression of TGF-β, Collagen-1, Snail, vimentin, FSP-1, CD68, TLR4, and MCP-1 and lower mRNA expression of E-cadherin. The U+C840 group had a significantly lower tubular injury score and interstitial fibrosis area fraction, which associated with downregulation of mRNA expression of TGF-β, Collagen-1, Snail, vimentin, FSP-1, CD68, TLR4, and MCP-1, with upregulation of mRNA expression of E-cadherin. Immunostaining observation revealed the U+C840 group demonstrated reduction of macrophage infiltration and myofibroblast expansion.Conclusion: CeA treatment with dose-dependently ameliorates mesenchymal transition and inflammation in kidney fibrosis in mice.

scholarly journals Rapamycin reduces renal hypoxia, interstitial inflammation and fibrosis in a rat model of unilateral ureteral obstruction

2014 ◽  
Vol 37 (3) ◽  
pp. 142 ◽  
Author(s):  
Chun-feng Liu ◽  
Hing Liu ◽  
Yi Fang ◽  
Su-hua Jiang ◽  
Jia-ming Zhu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Expression ◽  
Rat Model ◽  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Tubulointerstitial Fibrosis ◽  
Interstitial Inflammation ◽  
Mrna And Protein Expression ◽  
Tgf Β1

Purpose: The purpose of this study was to explore effects of rapamycin on renal hypoxia, interstitial inflammation and fibrosis, and the expression of transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), Flk-1 and Flt-1 in a rat model of unilateral ureteral obstruction (UUO). Methods: Male Sprague-Dawley rats (n=36) were randomly divided into three groups (n=12 per group): sham surgery, UUO and UUO plus rapamycin (0.2 mg/kg/d). Serum creatinine (Scr), blood urea nitrogen, uric acid, triglycerides, cholesterol and 24-h urine protein levels were measured. The extent of interstitial fibrosis was determined by Masson's trichrome staining. ED-1 positive macrophages, type III collagen, hypoxia, TGF-1, VEGF, Flk-1, and Flt-1 mRNA and protein expressions were detected using immunohistochemical staining, real-time PCR and Western blot. Results: UUO induced an elevation in Scr, renal hypoxia, inflammation, interstitial fibrosis, TGF-β1, VEGF, Flk-1, and Flt-1 mRNA and protein expression levels (P < 0.05). Rapamycin alleviated the UUO-induced renal hypoxia, infiltration of inflammatory cells and tubulointerstitial fibrosis (at days 3 and 7). Rapamycin also down-regulated the UUO-induced elevated expression levels of TGF-β1 and Flt-1 mRNA and protein (P < 0.05). Rapamycin decreased VEGF mRNA and protein expression at day 3, and increased Flk-1 mRNA and protein expression at day 7, compared with the UUO group (P < 0.05). Conclusion: Rapamycin shows beneficial effects by reducing UUO-induced renal hypoxia, inflammation and tubulointerstitial fibrosis.

scholarly journals Obstructive Nephropathy in the Mouse: Progressive Fibrosis Correlates with Tubulointerstitial Chemokine Expression and Accumulation of CC Chemokine Receptor 2- and 5-Positive Leukocytes

2001 ◽  
Vol 12 (6) ◽  
pp. 1173-1187 ◽  
Author(s):  
VOLKER VIELHAUER ◽  
HANS-JOACHIM ANDERS ◽  
MATTHIAS MACK ◽  
JOSEF CIHAK ◽  
FRANK STRUTZ ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Chemokine Receptor ◽  
Ureteral Obstruction ◽  
Unilateral Ureteral Obstruction ◽  
Tubulointerstitial Fibrosis ◽  
Leukocyte Migration ◽  
Obstructive Nephropathy ◽  
Cc Chemokine ◽  
Renal Tubulointerstitial Fibrosis ◽  
Cc Chemokines

Abstract. The infiltration of leukocytes plays a major role in mediating tubulointerstitial inflammation and fibrosis in chronic renal disease. CC chemokines participate in leukocyte migration and infiltration into inflamed renal tissue. Because CC chemokine-directed leukocyte migration is mediated by target cell expression of a group of CC chemokine receptors, this study examined the expression of CC chemokines and their receptors during initiation of tubulointerstitial fibrosis after unilateral ureteral obstruction in C57BL/6 mice. Obstructed kidneys developed hydronephrosis, tubular cell damage, interstitial inflammation, and fibrosis. From days 2 to 10, a progressive interstitial influx of F4/80+ macrophages and CD3+ lymphocytes occurred (macrophages, 4-fold; lymphocytes, 20-fold at day 10, compared with contralateral control kidneys). In parallel, the number of activated fibroblast-specific protein 1+ fibroblasts and interstitial collagen IV accumulation increased from days 2 to 10. The mRNA expression of CC chemokines (predominantly monocyte chemoattractant protein-1 [MCP-1]/CCL2, RANTES/CCL5) and their receptors CCR1, CCR2, CCR5 increased progressively from days 2 to 10. Byin situhybridization, a prominent interstitial mRNA expression of MCP-1 and RANTES and their receptors CCR2 and CCR5 localized to interstitial mononuclear cell infiltrates. MCP-1 and RANTES expression was also seen in tubular epithelial cells. Fluorescence-activated cell sorter analysis of single-cell suspensions from obstructed kidneys revealed a prominent expression of CCR2 and CCR5 by infiltrating macrophages, whereas most lymphocytes expressed CCR5 only. These data demonstrate an increased expression of MCP-1/CCL2 and RANTES/CCL5 at sites of tubulointerstitial damage and progressive fibrosis during unilateral ureteral obstruction that correlates with simultaneous accumulation of interstitial macrophages and T lymphocytes expressing the respective surface receptors CCR2 and CCR5. The chemokine receptor—mediated leukocyte influx into the tubulointerstitium could offer a new potential target for therapeutic intervention in progressive renal tubulointerstitial fibrosis.

Inhibition of CTCF-regulated miRNA-185-5p mitigates renal interstitial fibrosis of chronic kidney disease

Epigenomics ◽  
2021 ◽  
Author(s):  
Jiajun Zhou ◽  
Han Zhou ◽  
Yong Liu ◽  
Caixin Liu
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mouse Model ◽  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Renal Interstitial Fibrosis ◽  
Underlying Mechanisms

Aim: The present study aimed to elucidate the effect of CTCF on renal interstitial fibrosis in chronic kidney disease (CKD) and underlying mechanisms. Materials & methods: We measured NPHS2 expression and investigated its function in a unilateral ureteral obstruction-induced mouse model of CKD. Results: NPHS2 was poorly expressed in CKD mice. miR-185-5p targeted NPHS2 and reduced its expression, leading to increased α-SMA and COL I/III expression, increased renal interstitial fibrosis area and elevated phosphorylated vasodilator-stimulated phosphoprotein/vasodilator-stimulated phosphoprotein ratio. Cotreatment with CTCF downregulated miR-185-5p expression and abolished its effects in the CKD model. Conclusion: CTCF suppressed miR-185-5p and upregulated its target NPHS2, with a net effect of alleviating renal interstitial fibrosis in CKD.

Sustained-release prostacyclin analog ONO-1301 ameliorates tubulointerstitial alterations in a mouse obstructive nephropathy model

2012 ◽  
Vol 302 (12) ◽  
pp. F1616-F1629 ◽  
Author(s):  
Tatsuyo Nasu ◽  
Masaru Kinomura ◽  
Katsuyuki Tanabe ◽  
Hiroko Yamasaki ◽  
Su Le Htay ◽  
...  
Keyword(s):  
Sustained Release ◽  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Smooth Muscle Actin ◽  
Specific Protein ◽  
Unilateral Ureteral Obstruction ◽  
Obstructive Nephropathy ◽  
Therapeutic Effects ◽  
Proximal Tubular Epithelial Cells ◽  
Prostacyclin Analog

Tubulointerstitial injuries are crucial histological alterations that predict the deterioration of renal function in chronic kidney disease. ONO-1301, a novel sustained-release prostacyclin analog, accompanied by thromboxane synthase activity, exerts therapeutic effects on experimental pulmonary hypertension, lung fibrosis, cardiomyopathy, and myocardial ischemia, partly associated with the induction of hepatocyte growth factor (HGF). In the present study, we examined the therapeutic efficacies of ONO-1301 on tubulointerstitial alterations induced by unilateral ureteral obstruction (UUO). After inducing unilateral ureteral obstruction in C57/BL6J mice, a single injection of sustained-release ONO-1301 polymerized with poly (d,l-lactic-co-glycolic acid) sustained-release ONO-1301 (SR-ONO) significantly suppressed interstitial fibrosis, accumulation of types I and III collagen, increase in the number of interstitial fibroblast-specific protein-1 (FSP-1)+ cells, and interstitial infiltration of monocytes/macrophages (F4/80+) in the obstructed kidneys (OBK; day 7). Treatment with SR-ONO significantly suppressed the increase of the renal levels of profibrotic factor TGF-β and phosphorylation of Smad2/3, and elevated the renal levels of HGF in the OBK. In cultured mouse proximal tubular epithelial cells (mProx24), ONO-1301 significantly ameliorated the expression of fibroblast-specific protein-1 and α-smooth muscle actin as well as phosphorylation of Smad3 and increased the expression of zonula occludens-1 and E-cadherin in the presence of TGF-β1 as detected by immunoblot and immunocytochemistry, partly dependent on PGI2 receptor-mediated signaling. Administration of rabbit anti-HGF antibodies, but not the control IgG, partly reversed the suppressive effects of SR-ONO on tubulointerstitial injuries in the OBK. Taken together, our findings suggest the potential therapeutic efficacies of ONO-1301 in suppressing tubulointerstitial alterations partly mediated via inducing HGF, an antifibrotic factor counteracting TGF-β.

scholarly journals The effect of compound DM509 on kidney fibrosis in the conditions of the experimental model

2020 ◽  
Vol 80 (1) ◽  
pp. 10-15
Author(s):  
A. Stavniichuk ◽  
O. Savchuk ◽  
Abdul Hye Khan ◽  
Wojciech K. Jankiewicz ◽  
John D. Imig ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Control Group ◽  
Urea Nitrogen ◽  
Kidney Fibrosis

Kidney fibrosis is a key event in the development of chronic kidney disease, leading to end-stage renal failure. Unfortunately, there are now few drugs capable of preventing fibrosis in the kidneys, which is accompanied by the progression of chronic kidney disease in the terminal stage of renal failure. The results show the effectiveness of the use of a new dual-acting agent DM509 in the prevention of renal fibrosis using a model of unilateral obstruction of the ureter in mice. DM509 is both a farnesoid X-receptor agonist and a soluble epoxyhydrolase inhibitor. In this study, there were 8-12 week old C57BL/6J males undergoing surgery, which led to the development of unilateral ureteral obstruction and a control group. Mice received DM509 (10 mg/kg/day) or DM509-free solution together with drinking water for 10 days the day before surgery. Samples of kidney and blood tissues were collected at the end of the experiment. In the unilateral ureteral obstruction group, kidney dysfunction was detected, which was accompanied by increased urea nitrogen content in the blood compared to the control group (63 ± 7 vs. 34 ± 6 mg/d). The reduction of urea nitrogen in the blood by 36 % in mice with unilateral ureteral obstruction treated with DM509 is shown compared to mice with this pathology without treatment, which in turn proved the effectiveness of DM509 in preventing renal dysfunction. In mice with unilateral ureteral obstruction, which did not receive DM509, the development of kidney fibrosis with a high content of hydroxyproline in the kidneys and also increased collagen content in histological sections of the kidneys were detected. In the DM509 group, the renal and collagen hydroxyproline content was 34-66 % lower, indicating the effectiveness of this agent in the treatment of renal fibrosis. Thus, we have shown that the new DM509 is effective in preventing renal dysfunction and renal fibrosis using a murine model of unilateral ureteral obstruction.

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