UNILATERAL URETERAL OBSTRUCTION (UUO) is a clinical scenario that leads to obstructive nephropathy. UUO alters the expression of many mediators in the ipsilateral kidney. Renin-angiotensin system (RAS) is involved in UUO. Angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7) as the main arms of RAS influence kidney function which may alter by UUO. Ang II via Ang II receptor subtypes I (AT1R) reduces renal blood flow and glomerular filtration rate and induces oxidative stress, apoptosis as well as inflammation in renal tissue and contributes to renal fibrosis in UUO model. Also, Ang 1-7 receptor (MasR) and Ang II receptor subtype II (AT2R) may have a protective effect against UUO-induced renal injury. In addition, there is crosstalk among RAS with the main vasodilator factors (prostaglandins E2 and I2, bradykinin, atrial natriuretic factor, nitric oxide and adenosine) and the main vasoconstrictor factors (endothelin and vasopressin) in the ipsilateral kidney with UUO. In this review, the roles of the RAS on renal function and its interactions with the other factors in the kidney with UUO were discussed.

Introduction & Objective: Comparative reductase inhibitors, such as simvastatin increase HDL-cholestrol and decrease serum triglyceride and cholesterol. It is widely recognized that statins have organ protective nature and most effective for organ damage progressing. Obstructive uropathy can be used to indicate any OBSTRUCTION to urinary flow; which causes a developing of hydronephrosis, tubular atrophy and associated renal impairment. The aim of this study was evaluation of the simvastatin effect on renal fibrosis after UNILATERAL URETERAL OBSTRUCTION in rat.Materials & Methods: In this experimental study, 50 adult male Sprague-Dawley rats were subjected to UNILATERAL URETERAL OBSTRUCTION (UUO) and randomly divided into five groups (ten rats in each group) as follows: (1) control group; (2) UUO; (3) UUO/SIM; (4) Sham-operated; (5) Sham/SIM. Control animals received orally drug solvent by gavage for 15 days (started one day before operation). UNILATERAL URETERAL OBSTRUCTION was performed in groups 2 and 3 and sham operations were performed in groups 4 and 5. In group 2 animals received drug solvent and in group 3 animals received simvastatin (2 mg/kg/twice daily) for 15 days (started one day before operation). Rats were sacrificed either at day 14 for histopathological evaluation with H&E, masson-trichrome and PAS technique.Results: In this investigation histopathologic evaluation approved that in UUO group, renal interstitial fibrosis, tubular epithelial necrosis, hemorrhage, interstitial infiltration of mononuclear cells, tubular atrophy, glumerular tufts expanding, periglomerular sclerosis, subcapsular fibrosis, glomerulosclerosis and peritubular capillaries edema were observed. But in simvastatin treated animals this histopatologic lesions and fibrosis significantly (p<0.05) decreased. There was no difference between control and sham groups.Conclusion: In this investigation our results showed that URETERAL OBSTRUCTION increased renal fibrosis and caused severe deterioration in renal tissue but simvastatin administration improved renal fibrosis. It needs to be more investigation for approving of organ protective action of simvastatin in human renal disorders.

Objective(s): To explore the effect of verbascoside on renal fibrosis in UNILATERAL URETERAL OBSTRUCTION (UUO) rats. Materials and Methods: Twenty Sprague-Dawley rats were randomly distributed into sham-operated, UUO, and UUO+Verbascoside groups. After two weeks of rat model construction, urine and blood samples were collected for biochemical analysis while kidney tissues were harvested for hematoxylin and eosin (H&E), Masson’ s Trichrome, and immunohistochemistry staining. Pearson coefficient was used to analyze the correlation between the two proteins. Results: Verbascoside improved UUO-induced renal dysfunction as detected by decreased serum creatinine, urea nitrogen, and urinary protein excretion rate. In UUO rats, H&E staining result revealed increased total nucleated cell number, and Masson’ s Trichrome staining results showed tubular interstitial fibrosis with the deposition of collagen fibrils. Besides, expressions of fibrosis-related proteins including collagen type I (COL-I), α-smooth muscle actin (a-SMA), and tissue inhibitor of metalloproteinase 2 (TIMP2) expressed higher in the UUO group. Moreover, macrophage infiltrationrelated factors such as CD68+, F4/80+ cells, and suppressor of cytokine signaling-3 (SOCS3) were significantly higher in the UUO group than in sham-operated rats. However, after administration with verbascoside, the accumulation of collagen fibrils and total nucleated cell numbers were mitigated. Likewise, macrophage infiltration was extenuated and fibrosis-related proteins were down-regulated in the UUO+Verbascoside rats. Correlation analysis indicated that macrophage infiltration-related markers were related to fibrosis-related factors. Conclusion: Verbascoside could alleviate renal fibrosis in UUO rats probably through ameliorating macrophage infiltration.

flow. Losartan is angiotensin II receptor I (AT1) antagonist and is used for treatment of congestive heart failure and hypertension. It is widely recognized that Losartan has organ protective nature and most effective for organ damage progressing. The aim of this study was to evaluate the effect of Losartan on apoptosis in renal tissue after UNILATERAL URETERAL OBSTRUCTION in rat.Materials and Methods: In this experimental study, adult male Sprague-Dawley rats were randomly divided into five groups (ten rats in each group) as follows: (1) control; (2) UNILATERAL URETERAL OBSTRUCTION (UUO); (3) UUO/Losartan (UUO/LOS); (4) Sham-operated; (5) Sham/LOS. Control animals received drug solvent. UNILATERAL URETERAL OBSTRUCTION was performed in groups 2 and 3 and sham operations were performed in groups 4 and 5. In group 2, animals received drug solvent and in group 3 animals received Losartan (60 mg/kg). All drugs administered orally for 15 days (started before operation). Apoptosis in renal tissue were studied in left renal in different groups with tunnel method at day 14.Results: Tunnel staining determined that experimental UNILATERAL URETERAL OBSTRUCTION caused induction of apoptosis (15.52±1.33) in tubular cells of renal tissue but, in Losartan treated animals number of apoptotic cells (5.24±0.93) significantly (p<0.05) decreased. There was no significant difference between control (0.91±0.26), sham (1.17±0.29) and sham/LOS (2.16±0.47) groups.Conclusion: Our results showed that experimental UNILATERAL URETERAL OBSTRUCTION induces apoptosis in renal tissue but, Losartan administration decreased the number of apoptotic cells in renal tissue.

Background: It is widely recognized that losartan, as an angiotensin receptor (AT1) antagonist, has organ protective nature and effective activity against organ damage progression. The aim of this study was to evaluate the effect of losartan on renal function amelioration after UNILATERAL URETERAL OBSTRUCTION of rat.Material and methods: In this experimental study, 50 Adult male Sprague-Dawley rats were subjected to UNILATERAL URETERAL OBSTRUCTION (UUO) of left kidney and randomly divided into five groups (ten rats in each groups) as follows: (1) control group; (2) UUO; (3) UUO/LOS; (4) Sham-operated; (5) Sham/LOS. Control animals received orally drug solvent by gavage for 15 days. UNILATERAL URETERAL OBSTRUCTION was performed on groups 2 and 3 and sham, the operation was performed in groups 4 and 5. The group 2, received solvent drug and group 3 received losartan (60 mg/kg) for 15 days. Blood samples were collected at day 0, 3, 7 and 14 after UUO for evaluation of serum creatinine, urea and cholesterol levels. Rats were sacrificed at day 14 for histopathological evaluation of left kidney with H&E technique. Data were analyzed by ANOVA statistics.Results: Serum creatinine, urea and cholesterol levels significantly increased in UUO group at days 7 and 14 after operation compared with control group (p<0.05). But serum levels of creatinine, urea and cholesterol significantly decreased (p<0.05). Unlike losaratan treated animals, histopathologic evaluation showed more renal interstitial fibrosis, tubular epithelial necrosis, hemorrhage, interstitial infiltration of mononuclear cells, tubular atrophy, glumerular tufts expanding, periglomerular sclerosis, subcapsular fibrosis, glomerulosclerosis and peritubular capillaries edema in UUO groups. There were no significant differences between control and sham groups.Conclusion: This study showed the URETERAL OBSTRUCTIONs lead severe renal tissue deterioration and dysfunction, but losartan may reverse renal tissue damage.

Objective (s): Our recent report indicates that breviscapine play a protective role of the kidney by down-regulating transforming growth factor- b 1 (TGF-b1), a-smooth muscle actin (a-SMA) and alleviating interstitial fibrosis following UNILATERAL URETERAL OBSTRUCTION (UUO). In this study, we investigate the effect of breviscapine on changes of renal water and sodium transport proteins in response to UUO.Materials and Methods: Male Sprague-Dawley rats were divided into 3 groups, sham group, UUO group and UUO treat with breviscapine. After 4, 7 and 14 days, histologic changes and interstitial collagen were determined microscopically following hematoxylin and eosin (H& E) and Masson's trichrome staining. The expression of Aquaporins (AQP-2) and g-epithelial sodium channel (g-ENaC) were investigated using immunohistochemistry and Western blot in each group.Results: Breviscapine treatment decrease the tubular injury index and the degree of interstitial collagen deposition significantly compared with the UUO group (P<0.05). Breviscapine treatment also significantly reduced downregulation of AQP2 and g-ENaC compared to those subjected to the same time course of OBSTRUCTION in UUO group (P<0.05).Conclusion: These results demonstrate that breviscapine could prevent downregulation of renal water and sodium transport proteins in response to UUO so as to protect obstructed kidney.