Overexpression of NDUFV1 alleviates renal damage by improving mitochondrial function in unilateral ureteral obstruction model mice

Author(s):  
Ruiting Wang ◽  
Chen Kairen ◽  
Lu Li ◽  
Lingling Zhang ◽  
Haifeng Gong ◽  
...  

2008 ◽  
Vol 295 (5) ◽  
pp. F1545-F1553 ◽  
Author(s):  
Yasunori Mizuguchi ◽  
Jie Chen ◽  
Surya V. Seshan ◽  
Dix P. Poppas ◽  
Hazel H. Szeto ◽  
...  

Unilateral ureteral obstruction (UUO) is characterized by decreases in renal function, increased interstitial fibrosis, tubular apoptosis, and cellular infiltration. It has been suggested that inhibition of tubular apoptosis may protect against renal damage in obstruction. We have recently developed a series of peptides which are concentrated in the inner mitochondrial membrane and prevent cell death. These peptides are also active in vivo, in myocardial infraction, ischemic brain injury, and amyotrophic lateral sclerosis models. We therefore used SS-31, a prototype of these peptides, and assessed its effects on renal damage and oxidative stress in a 14-day obstruction model. SS-31 (1 or 3 mg/kg) or saline was given 1 day before and throughout the 14 days of obstruction. Kidneys were harvested and assessed for apoptosis (terminal transferase-dUTP-nick-end labeling, caspase 3 expression), fibrosis (trichrome staining), macrophage infiltration, fibroblast expression (immunoperoxidase), and oxidative damage (8-OH deoxyguanosine and heme oxygenase-1 expression), cytokines, and signaling pathways (transforming growth factor-β, CCR-1, p38-MAPK, NF-κB). SS-31 significantly attenuated the effects of obstruction on all aspects of renal damage which were examined, with both the 1 and 3 mg/kg doses showing efficacy. We noted increased oxidative stress in obstruction, which was also attenuated by SS-31 treatment. Signaling via NF-κB and p38 MAPK pathways were both affected by SS-31 treatment. This study provides a proof of concept that peptides which protect mitochondria in vitro can provide protection from renal damage in a UUO model. The mechanism by which protection is afforded requires further studies both in vitro and in vivo.



Urology ◽  
2009 ◽  
Vol 74 (4) ◽  
pp. 938-943 ◽  
Author(s):  
Yasumitsu Uchida ◽  
Akira Miyajima ◽  
Eiji Kikuchi ◽  
Norihide Kozakai ◽  
Takeo Kosaka ◽  
...  


2018 ◽  
Vol 44 (6) ◽  
pp. 1243-1251 ◽  
Author(s):  
Emre Can Polat ◽  
Huseyin Besiroglu ◽  
Levent Ozcan ◽  
Alper Otunctemur ◽  
Ahmet Tugrul Eruyar ◽  
...  


2005 ◽  
Vol 68 (2) ◽  
pp. 515-528 ◽  
Author(s):  
Keiichi Ito ◽  
J.I.E. Chen ◽  
Surya V. Seshan ◽  
Jonathan J Khodadadian ◽  
Rachel Gallagher ◽  
...  


2012 ◽  
Vol 1 (2) ◽  
Author(s):  
Alvarino Alvarino

AbstrakPendahuluan : Obstruksi ureter merupakan kondisi yang dapat terjadi pada setiap usia dengan levelbervariasi dengan efek terburuk berupa gagal ginjal permanen. Terdapat berbagai mekanisme yang berperandalam terjadinya kerusakan ginjal pada obstruksi ureter. Penelitian ini bertujuan untuk mengamati pengaruhvalsartan untuk memperbaiki kerusakan ginjal pada kondisi tersebut. Metode : Dilakukan penelitian eksperimentalmenggunakan 30 ekor tikus wistar dengan obstruksi ureter unilateral melalui pengikatan ureter kiri yang dibagimenjadi dua kelompok, tanpa pemberian valsartan dan dengan pemberian valsartan. Pada hari ke-14 dinilai dandibandingkan fibrosis interstisial, degenerasi hidrofik, dan atrofi tubulus pada kedua kelompok dengan pulasanhematoksilin-eosin. Hanya tikus yang tetap hidup hingga melewati hari ketujuh yang dimasukkan dalam penelitian.Hasil : Dari tiga belas tikus wistar pada kelompok obstruksi ureter unilateral tanpa pemberian valsartan, didapatkan11 tikus mengalami fibrosis interstisial pada ringan dan 2 tikus mengalami fibrosis interstisial sedang, sementaraseluruh tikus wistar pada kelompok dengan valsartan mengalami fibrosis interstisial ringan (p > 0.05). Tidakterdapat perbedaan bermakna untuk degenerasi hidrofik epitel tubulus antara kelompok tanpa valsartan dandengan valsartan (31.46 vs 33.67, p > 0.05). Tidak terdapat pula perbedaan bermakna untuk atrofi tubuli antarakedua kelompok (61.78 vs 62.07, p > 0.05). Kesimpulan : Pemberian valsartan dengan dosis antihipertensi tidakmengurangi tingkat fibrosis interstisial, degenerasi hidrofik, maupun atrofi tubulus pada obstruksi ureter unilateralpada tikus wistarKata kunci: obstruksi ureter unilateral, valsartan, fibrosis interstisialAbstractIntroduction: Ureteral obstruction is a condition that might happen at any age in any level with the worstcomplication is permanent renal damage. There are several mechanisms that play role in renal damage in ureteralobstruction. This experimental research is aimed to observe the effect of valsartan to attenuate renal damage inunilateral ureteral obstruction. MethodsExperimental research was performed using 30 wistar rats with unilateralureteral obstruction achieved by ligation of the left ureter. Rats then divided into two groups, no treatment groupand valsartan group. At the 14th day, evaluation was performed to compare interstitial fibrosis, hydrophilicdegeneration, and tubular atrophy between the two groups using haematoxylin-eosin staining. Only rats surviveuntil at least 7th day are included in the study. ResultFrom thirteen wistar rats in no treatment group, two of themhaving moderate interstitial fibrosis and eleven with mild interstitial fibrosis while all rats in valsartan group had mildinterstitial fibrosis (p > 0.05). There is no significant difference on hydrophilic degeneration between no treatmentand valsartan group (31.46 vs 33.67, p > 0.05). There is also no significant difference in tubular atrophy betweenthe two groups (61.78 vs 62.07, p > 0.05). ConclusionValsartan therapy in antihypertensive dosage has nosignificant effect in to attenuate interstitial fibrosis, hydrophilic degeneration, and tubular atrophy in unilateralureteral obstruction in wistar rats.Keywords: unilateral ureteral obstruction, valsartan, interstitial fibrosis



2015 ◽  
Vol 7 (2) ◽  
pp. 166 ◽  
Author(s):  
Alper Otunctemur ◽  
Emin Ozbek ◽  
SuleymanSami Cakir ◽  
EmreCan Polat ◽  
Murat Dursun ◽  
...  


2017 ◽  
Vol 69 (4) ◽  
pp. 648-657 ◽  
Author(s):  
Sara Hosseinian ◽  
Abolfazl Khajavi Rad ◽  
Alireza Ebrahimzadeh Bideskan ◽  
Mohammad Soukhtanloo ◽  
Hamidreza Sadeghnia ◽  
...  


2004 ◽  
Vol 287 (6) ◽  
pp. F1283-F1293 ◽  
Author(s):  
Keiichi Ito ◽  
Jie Chen ◽  
Maher El Chaar ◽  
Joshua M. Stern ◽  
Surya V. Seshan ◽  
...  

Progression of renal damage after relief of unilateral ureteral obstruction (UUO) has been demonstrated, especially in neonatal rats. We evaluated renal function and renal damage after relief of 3-day UUO in five groups of adult rats: group 1, no treatment; group 2, 3-day UUO; groups 3- 5, 3-day UUO followed by relief; group 3, 7-day relief; group 4, 14-day relief; and group 5, 28-day relief. Glomerular filtration rate (GFR), renal blood flow (RBF), tissue transforming growth factor-β (TGF-β), interstitial fibrosis and fibroblast expression, tubular apoptosis, macrophage infiltration, expression of nitric oxide synthases (NOS), and urinary nitrate/nitrite (NO2/NO3) were evaluated. RBF and GFR were decreased to <10% of baseline by 3 days of UUO. GFR and RBF in a previously obstructed kidney (POK) returned to baseline by 14 days after relief. Both tissue TGF-β1 and interstitial fibrosis were significantly higher in POK of groups 3- 5 compared with groups 1 and 2 . In group 5, the numbers of infiltrating macrophages, fibroblasts, and apoptotic tubular cells were higher in POK compared with group 1. Urinary NO2/NO3 was significantly higher than baseline from 3 to 27 days after relief of UUO. Expression of NOS isoforms was increased in tubules. As interstitial fibrosis contributes to decreased renal function, these results suggest that the acute recovery in function may be compromised in the long term by the progressive renal fibrosis which was found. Furthermore, pharmacological intervention at the time of relief of UUO, targeted to fibrotic processes, may contribute to long-term recovery of renal function.



Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 671
Author(s):  
Rodrigo Prieto-Carrasco ◽  
Alejandro Silva-Palacios ◽  
Pedro Rojas-Morales ◽  
Omar Emiliano Aparicio-Trejo ◽  
Estefany Ingrid Medina-Reyes ◽  
...  

Our work evaluated cardiac function and mitochondrial bioenergetics parameters in hearts from male Wistar rats subjected to the UUO model during 28 days of progression. We measured markers of kidney damage and inflammation in plasma and renal fibrosis by histological analysis and Western blot. Cardiac function was evaluated by echocardiography and proteins involved in cardiac damage by Western blot. Oxygen consumption and transmembrane potential were monitored in cardiac mitochondria using high-resolution respirometry. We also determined the activity of ATP synthase and antioxidant enzymes such as glutathione peroxidase, glutathione reductase, and catalase. Our results show that, although renal dysfunction is established in animals subjected to ureteral obstruction, cardiac function is maintained along with mitochondrial function and antioxidant enzymes activity after 28 days of injury evolution. Our results suggest that renocardiac syndrome might develop but belatedly in obstruction-induced renal damage, opening the opportunity for treatment to prevent this condition.



Sign in / Sign up

Export Citation Format

Share Document