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1.
Urol Oncol ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31983531

RESUMO

OBJECTIVE: To investigate the role of gene expression of circulating tumor cells (CTCs) as noninvasive prognostic markers in patients with high risk nonmuscle invasive bladder cancer. MATERIALS AND METHODS: We identified all patients with TIG3 urothelial bladder cancer (UBC) at our institution since 2016.The study included 100 patients with T1G3 UBC and 50 healthy volunteers. CTCs were isolated from blood using immunomagnetic separation and gene expression was performed using 10 bladder cancer associated genes, namely; KRAS, EPCAM, CD133, CD44, mTOR, SURVIVIN, AKT, PI3K, VEGF, and TP53. Gene expression of CTCs was correlated to time to first recurrence and time to progression using Kaplan-Meier curves. RESULTS: There was strong negative correlation between CTCs-positive patients and time to first recurrence and time to progression. Significant differences in expression levels of specific genes were observed that can predict recurrence and progression of T1G3 UBC. CONCLUSION: CTCs appear to be noninvasive methods of predicting disease recurrence and progression in patients with high- risk nonmuscle invasive bladder cancer; therefore, studying their molecular profiling may improve prediction of recurrence and progression. Further studies are invited for more in-depth investigation to consolidate our initial results.

2.
Arab J Urol ; 17(2): 150-159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31285928

RESUMO

Objectives: To design a new canine model to assess the renoprotective effect of local sildenafil administration, as the renoprotective effect of systemic sildenafil administration in renal ischaemia-reperfusion (IR) injury in animal models has been shown but its local effects have not been established to date. Materials and methods: In all, 120 dogs were assigned to five groups: sham, oral control (OC) group (right nephrectomy + left renal ischaemia for 60 min), oral sildenafil (OS) group (oral sildenafil 1 mg/kg, 60 min before ischaemia), local control (LC) group (local renal perfusion with saline and heparin for 5 min) and local sildenafil (LS) group (perfusion with sildenafil 0.5 mg/kg). Renal functions, histopathological changes, expression of caspase-3, nuclear factor erythroid 2-related factor 2 (Nrf2), inflammatory cytokines (intracellular adhesion molecule 1, tumour necrosis factor α and interleukin 1ß) and endothelial nitric oxide synthase (eNOS) in renal tissues were assessed in all groups at 1, 3, 7 and 14 days. Results: There were significant improvements in renal functions and cortical and medullary damage scores in the sildenafil-treated groups compared to their control groups (P < 0.05). Also, the LS group showed significantly better improvement of renal functions and cortical and medullary damage scores than the OS group (P < 0.05). Moreover, sildenafil significantly decreased the expression of caspase-3 and inflammatory cytokines and increased the expression of Nrf2 and eNOS in renal tissue, which were statistically significant in the LS group. Conclusion: LS has a greater renoprotective effect against renal IR injury than systemic administration via anti-inflammatory, antioxidant and anti-apoptotic pathways. Abbreviations: BUN: blood urea nitrogen; Ct: cycle threshold; eNOS: endothelial nitric oxide synthase; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; H&E: haematoxylin and eosin; IL-1ß: interleukin 1ß; NO: nitric oxide; Nrf2: nuclear factor erythroid 2-related factor 2; OC: oral control; OS: oral sildenafil; LC: local control; LS: local sildenafil.

3.
BMC Urol ; 18(1): 100, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413194

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) overexpression is believed to be associated with bladder cancer (BC) progression and poor clinical outcomes. In vivo studies have linked EGFR subcellular trafficking and chemo-resistance to cisplatin-based chemotherapies. This has not been studied in the clinical adjuvant setting. We aimed to investigate the prognostic significance of EGFR expression in patients receiving cisplatin-based adjuvant chemotherapy following radical cystectomy for advanced BC. METHODS: The database from the Urology and Nephrology Center at Mansoura University was reviewed. BC patients who were treated with radical cystectomy and adjuvant chemotherapy for adverse pathological features or node positive disease were identified. Patients who underwent palliative cystectomy, had histological diagnoses other than pure urothelial carcinoma, or received adjuvant radiotherapy were excluded from the study. Immunohistochemical staining for EGFR expression was performed on archived bladder specimens. The following in vitro functional analyses were performed to study the relationship of EGFR expression and chemoresponse. RESULTS: The study included 58 patients, among which the mean age was 57 years old. Majority of patients had node positive disease (n = 53, 91%). Mean follow up was 26.61 months. EGFR was overexpressed in 25 cystectomy specimens (43%). Kaplan-Meier analysis revealed that EGFR over-expression significantly correlated with disease recurrence (p = 0.021). Cox proportional hazard modeling identified EGFR overexpression as an independent predictor for disease recurrence (p = 0.04). Furthermore, in vitro experiments demonstrated that inhibition of EGFR may sensitize cellular responses to cisplatin. CONCLUSIONS: Our findings suggest that EGFR overexpression is associated with disease recurrence following adjuvant chemotherapy for advanced BC. This may aid in patient prognostication and selection prior to chemotherapeutic treatment for BC.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fator de Crescimento Epidérmico/biossíntese , Regulação Neoplásica da Expressão Gênica , Neoplasias Musculares/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/fisiologia , Fator de Crescimento Epidérmico/genética , Receptores ErbB/biossíntese , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/tratamento farmacológico , Invasividade Neoplásica/patologia , Valor Preditivo dos Testes , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética
4.
BJU Int ; 119(1): 142-147, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27686059

RESUMO

OBJECTIVE: To evaluate the protective effects of selenium with vitamins A, C and E (selenium ACE, i.e. antioxidants), verapamil (calcium channel blocker), and losartan (angiotensin receptor blocker) against extracorporeal shockwave lithotripsy (ESWL)-induced renal injury. PATIENTS AND METHODS: A randomised controlled trial was conducted between August 2012 and February 2015. Inclusion criteria were adult patients with a single renal stone (<2 cm) suitable for ESWL. Patients with diabetes, hypertension, congenital renal anomalies, moderate or marked hydronephrosis, or preoperative albuminuria (>300 mg/L) were excluded. ESWL was performed using the electromagnetic DoLiS lithotripter. Eligible patients were randomised into one of four groups using sealed closed envelopes: Group1, control; Group 2, selenium ACE; Group 3, losartan; and Group 4, verapamil. Albuminuria and urinary neutrophil gelatinase-associated lipocalin (uNGAL) were estimated after 2-4 h and 1 week after ESWL. The primary outcome was differences between albuminuria and uNGAL. Dynamic contrast-enhanced magnetic resonance imaging was performed before ESWL, and at 2-4 h and 1 week after ESWL to compare changes in renal perfusion. RESULTS: Of 329 patients assessed for eligibility, the final analysis comprised 160 patients (40 in each group). Losartan was the only medication that showed significantly lower levels of albuminuria after 1 week (P < 0.001). For perfusion changes, there was a statistically significant decrease in the renal perfusion in patients with obstructed kidneys in comparison to before ESWL (P = 0.003). These significant changes were present in the control or antioxidant group, whilst in the losartan and verapamil groups renal perfusion was not significantly decreased. CONCLUSIONS: Losartan was found to protect the kidney against ESWL-induced renal injury by significantly decreasing post-ESWL albuminuria. Verapamil and losartan maintained renal perfusion in patients with post-ESWL renal obstruction.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Antioxidantes/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Rim/lesões , Litotripsia/efeitos adversos , Losartan/uso terapêutico , Selênio/uso terapêutico , Verapamil/uso terapêutico , Vitaminas/uso terapêutico , Adulto , Ácido Ascórbico/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Vitamina A/uso terapêutico , Vitamina E/uso terapêutico , Ferimentos e Lesões/prevenção & controle
5.
Can J Physiol Pharmacol ; 94(9): 936-46, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27411029

RESUMO

The present study investigated the effects of combination of ischemic preconditioning (Ipre) and adipose-derived mesenchymal stem cells (ADMSCs) on renal ischemia-reperfusion (I-R) injury in rats. 90 male Sprague Dawley rats were divided into 5 equal groups; sham operated, control (45 min left renal ischemia), Ipre group as control group with 3 cycles of Ipre just before renal ischemia, ADMSCs-treated group (as control with ADMSCs 10(6) cells in 0.1 mL via penile vein 60 min before ischemia time), and Ipre + ADMSCs group as ADMCs group with 3 cycles of Ipre. Ipre and ADMSCs groups showed significant decrease in serum creatinine and blood urea nitrogen (BUN) and caspase-3 and CD45 expression in kidney and significant increase in HIF-1α, SDF-1α, CD31, and Ki67 expressions in kidney compared with the control group (p < 0.05). Moreover, the Ipre + ADMSCs group showed significant decrease in serum BUN and caspase-3 and CD45 expression in kidney with significant increase in HIF-1α, SDF-1α, CD31, and Ki67 expression in kidney compared with the Ipre and ADMCs groups (p < 0.05). We concluded that Ipre potentiates the renoprotective effect of ADMSCs against renal I/R injury probably by upregulation of HIF-1α, SDF-1α, CD31, and Ki67 and downregulation of caspase-3 and CD45.


Assuntos
Tecido Adiposo/citologia , Precondicionamento Isquêmico , Rim/metabolismo , Rim/patologia , Transplante de Células-Tronco Mesenquimais , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Animais , Nitrogênio da Ureia Sanguínea , Caspase 3/biossíntese , Quimiocina CXCL12/biossíntese , Creatinina/sangue , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Antígeno Ki-67/biossíntese , Antígenos Comuns de Leucócito/biossíntese , Masculino , Molécula-1 de Adesão Celular Endotelial a Plaquetas/biossíntese , Ratos , Traumatismo por Reperfusão/sangue
6.
Gen Physiol Biophys ; 35(1): 77-86, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26612920

RESUMO

The mechanisms underlying the renoprotective effect for remote limb ischemic preconditioning (rIPC) against renal ischemia/reperfusion injury need further elucidation. In our work, one hundred and twenty male Sprague Dawley rats were randomized into 3 groups; sham, I/R group (left renal 45 min ischemia) and rIPC (as I/R group with 3 cycles of left femoral ischemic PC just before renal ischemia). Rats were sacrificed at 2 h, 24 h, 48 h and 7 days. Serum creatinine and urea were measured at the baseline and endpoints. Also, histopathological examination and assessment of the expression of inflammatory cytokines e.g. TNF-α, IL-1ß and ICAM-1 and antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 in left kidney were done by the end of experiment. The results of this study demonstrated that, rIPC caused significant improvement in serum creatinine and BUN levels and in the expression of antioxidant genes and Bcl-2 antiapoptotic gene with significant attenuation of pro-inflammatory cytokines and histopathological damage score at all-time points compared to I/R group (p ≤ 0.05). In conclusion, inhibition of inflammatory cytokine (TNF-α, IL-1ß and ICAM-1) formation and activation of antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 could be possible underlying mechanisms for the renoprotective effect of rIPC.


Assuntos
Antioxidantes/metabolismo , Citocinas/imunologia , Fatores Imunológicos/sangue , Precondicionamento Isquêmico/métodos , Nefropatias/fisiopatologia , Traumatismo por Reperfusão/fisiopatologia , Animais , Proteínas Reguladoras de Apoptose , Membro Posterior/irrigação sanguínea , Nefropatias/sangue , Nefropatias/prevenção & controle , Testes de Função Renal , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/prevenção & controle , Resultado do Tratamento
7.
Int Urol Nephrol ; 47(11): 1907-15, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26377490

RESUMO

OBJECTIVES: To study the possible renoprotective effect of sildenafil against renal ischemia/reperfusion (I/R) injury and its effect on the expression of some antioxidant, antiapoptotic gene and proinflammatory cytokine genes in rat model of renal I/R injury. MATERIALS AND METHODS: One hundred and twenty male Sprague Dawley rats were subdivided into three equal groups: sham (underwent right nephrectomy without ischemia), control (underwent right nephrectomy and left ischemia for 45 min) and study [as control with 1 mg/kg sildenafil (per oral) 60 min before anesthesia]. Serum creatinine and BUN were measured at the baseline and the study endpoints (2, 24, 48 h and 7 days), and the left kidney was harvested at study endpoints for histopathological examination as well as for assessment of the expression of antioxidant genes (Nrf-2, HO-1 and NQO-1), antiapoptotic gene (Bcl-2) and inflammatory cytokines, e.g., TNF-a, IL-1ß and ICAM-1. RESULTS: I/R caused significant increase in serum creatinine, BUN, histopathological damage score (p < 0.001) and significant reduction in antioxidant genes (nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) with significant increase in TNF-a, IL-1ß and ICAM-1 genes in kidney tissues. Pretreatment with sildenafil caused significant attenuation of serum creatinine and BUN as well as significant increase in the expression of antioxidant genes and Bcl-2 genes with significant reduction in the expression of proinflammatory cytokine genes (p value < 0.001). CONCLUSION: The renoprotective effect of sildenafil against renal I/R might be due to the activation of antioxidant genes (Nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) and attenuation of proinflammatory cytokines (TNF-a, IL-1ß and ICAM-1).


Assuntos
Inibidores da Fosfodiesterase 5/farmacologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/prevenção & controle , Citrato de Sildenafila/farmacologia , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Molécula 1 de Adesão Intercelular/genética , Interleucina-1beta/genética , Masculino , NAD(P)H Desidrogenase (Quinona)/genética , Fator 2 Relacionado a NF-E2/genética , Nefrectomia , Inibidores da Fosfodiesterase 5/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Citrato de Sildenafila/uso terapêutico , Fator de Necrose Tumoral alfa/genética , Isquemia Quente/efeitos adversos
8.
Infect Agent Cancer ; 8(1): 24, 2013 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-23809295

RESUMO

OBJECTIVE: The present study was designed to determine the possible impact of hepatitis C virus (HCV) infection on the expression of telomerase (TERT), retinoblastoma (RB1), E2F3, TP53, CDKN1A (p21) and fibroblast growth factor receptor- 3 (FGFR3) genes in patients with bladder cancer (BC). MATERIALS AND METHODS: 100 patients with bladder cancer (15 female and 85 male) were divided into 2 groups; Group I: 50 HCV negative subjects (age range 36-79), and Group II: 50 HCV positive subjects (age range 42-80). Expressions of the telomerase, retinoblastoma (Rb), E2F3, TP53 and FGFR3 genes were tested by immunohistochemistry and real time PCR in tumour tissues and healthy bladder tissues. Also, telomerase activity was assessed by telomeric repeats amplification protocol (TRAP). RESULTS: Bladder tumors associated with HCV infection were of high grade and invasive squamous cell carcinomas (SCCs). Expressions of hTERT, Rb, E2F3, TP53 and FGFR3 as well as telomerase activity were significantly higher in bladder tissues of HCV-infected patients compared with bladder tissues of non infected patients (p<0.05). On the contrary, CDKN1A (p21) expression was significantly lower in bladder tissues of HCV-infected patients compared to bladder tissues of non infected patients (p<0.05). CONCLUSION: The expressions of hTERT, Rb, E2F3, TP53 and FGFR3 as well as the activity of telomerase were significantly high in malignant bladder tissues associated with HCV infection. On the other hand, CDKN1A (p21) expression was low in bladder tissues of HCV-infected subjects. Moreover, there was a positive correlation between HCV infection and expression of telomerase, E2F3, TP53 and FGFR3. There was a negative correlation between HCV infection and expression of Rb and p21.

9.
Can J Physiol Pharmacol ; 90(11): 1535-43, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23181281

RESUMO

The objective of this study was to investigate the effects of erythropoietin (EPO) on systemic and renal hemodynamics in a rat model of renal ischemic/reperfusion (I/R) injury. We used 30 male Sprague-Dawley rats distributed among the following 3 groups (10 rats per group): (i) the sham-operated group, (ii) the control group (I/R injury only), and (iii) the EPO-treated group (I/R injury with 1500 U EPO·(kg body mass)⁻¹ on day 0, and 500 U·kg⁻¹ on days 2 and 4 after ischemia). Renal function, arterial blood pressure (ABP), renal plasma flow (RPF), renal blood flow (RBF), and renal vascular resistance (RVR) were measured on days 1, 2, and 7 after ischemia. The expression of endothelial NO synthase (eNOS) and histopathology of kidney were evaluated on day 7. The contractility of aortic strips was recorded from the different groups. The results show that renal function and histopathology were significantly improved after treatment with EPO. Compared with the control group, the EPO-treated group showed a significant increase in RPF, RBF, haematocrite, ABP, eNOS expression, and a decrease in RVR (p < 0.05).The response of aortic strips to the relaxant effect of acetylcholine was improved in the EPO-treated group. In conclusion, treatment with EPO improves renal function and renal haemodynamics in renal I/R injury, and causes significant rise of ABP and haematocrite value.


Assuntos
Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Hipotensão/prevenção & controle , Isquemia/tratamento farmacológico , Rim/efeitos dos fármacos , Circulação Renal/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiopatologia , Resistência a Medicamentos/efeitos dos fármacos , Indução Enzimática/efeitos dos fármacos , Epoetina alfa , Eritropoetina/efeitos adversos , Hematínicos/efeitos adversos , Hemodinâmica/efeitos dos fármacos , Hipotensão/etiologia , Rim/irrigação sanguínea , Rim/patologia , Rim/fisiopatologia , Masculino , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo III/biossíntese , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Substâncias Protetoras/efeitos adversos , Substâncias Protetoras/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Resistência Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
10.
BJU Int ; 110(6): 904-11, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22381210

RESUMO

UNLABELLED: What's known on the subject? and What does the study add? It is known that the kidney damage continues even after release of ureteric obstruction. This study found that giving ferulic acid, antioxidant, after release of ureteric obstruction enhanced the recovery of kidney functions in solitary kidney. OBJECTIVE: To evaluate the effect of ferulic acid (FA) on the recovery of renal function and renal damage after relief of partial ureteric obstruction (PUO) of a solitary kidney. METHODS: Male mongrel dogs (n = 32) were classified into three groups: sham (eight), control (12) and study (12). A right nephrectomy was carried out and dogs in the study and control groups were subjected to 4 weeks of PUO. Serum creatinine, creatinine clearance (CrCl) and renographic clearance (RC) were measured at baseline, after 4 weeks of obstruction and 8 weeks after relief of obstruction. Markers of lipid peroxidation (malondialdehyde [MDA]), superoxide dismutase (SOD), and reduced glutathione (GSH), and immunostaining of markers of apoptosis (caspase 3 and Bcl2), cell proliferation (Ki67) and interstitial fibrosis in the kidney were evaluated at the end of experiment. RESULTS: Ferulic acid enhanced the recovery of serum creatinine, CrCl and RC by an extra 22%, 26% and 33.7%, respectively, of the basal values at 8 weeks, after relief of 4 weeks' obstruction. In addition, FA caused a significant decrease in MDA and a significant increase in GSH and SOD. Ferulic acid also significantly reduced the interstitial fibrosis, and caspase 3 expression, and significantly increased the expression of Bcl2 and Ki67 in kidney tissues at 8 weeks after relief of the obstruction. CONCLUSION: Ferulic acid enhances the recoverability of renal function and minimizes the renal damage through reduction of oxidative stress, tubular apoptosis and the interstitial fibrosis in the solitary kidney after relief of PUO.


Assuntos
Ácidos Cumáricos/farmacologia , Nefropatias/etiologia , Nefropatias/fisiopatologia , Rim/efeitos dos fármacos , Rim/fisiologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Obstrução Ureteral/complicações , Animais , Cães , Rim/anormalidades , Masculino
11.
Arab J Urol ; 10(4): 418-24, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26558061

RESUMO

OBJECTIVE: To compare the effect of ischaemic preconditioning (Ipre) vs. ischaemic postconditioning (Ipost) on renal ischaemia/reperfusion (I/R) injury in rats. MATERIALS AND METHODS: In all, 120 male Sprague-Dawley rats were classified into four groups of 30 rats each, designated sham, control, Ipre and Ipost. Renal function, including serum creatinine, blood urea nitrogen (BUN), creatinine clearance (CrCl), fractional Na excretion (FENa) and renal histopathology were measured at 2, 24 and 48 h after ischaemia. Markers of lipid peroxidation (malondialdehyde, MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were measured in kidney tissues during the same intervals. RESULTS: Ipre caused a significant improvement in renal function, as indicated by a significant decrease in serum creatinine, BUN and FENa, with a significant increase in CrCl. However, Ipost caused no significant improvement in renal function. Morphologically Ipre caused a marked significant improvement in the renal tubular damage score compared to Ipost. Also, Ipre caused a significant decrease in MDA, and significant increase in GSH and SOD when compared to Ipost. CONCLUSION: Ipre is more potent than Ipost for improving the renal injury induced by I/R. Ipre caused a marked improvement in renal function and morphology, while Ipost caused a minimal improvement in morphology only. Moreover, Ipre caused a marked and significant reduction in oxidative stress in kidney tissues, while Ipost caused a minimal reduction.

12.
BJU Int ; 108(4): 612-8, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21592301

RESUMO

UNLABELLED: What's known on the subject? and What does the study add? Renal ischaemia/reperfusion (I/R) injury is an inevitable consequence of kidney transplantation. It contributes to delayed graft function (DGF), acute renal failure and graft rejection. The present study investigates for the first time the impact of a combination of L-arginine and alpha tocopherol on the renal ischemia/reperfusion injury in a rodent model of kidney transplantation. We found that concomitant administration of L-arginine and α-tocopherol has a more protective effect and synergistic antioxidant effect on ischaemia/reperfusion injury in transplanted rat kidneys. OBJECTIVES: To investigate the role of L-arginine and α-tocopherol in ischaemia/reperfusion injury in a kidney transplanted rat model. MATERIALS AND METHODS: In total, 40 male Sprague-Dawley rats subjected to renal transplantation received FK506 (tacrolimus) to overcome early acute rejection episodes. Animals were divided randomly into four groups (ten rats each). Group I were treated with FK506 (2 mg/kg/bw/day) and served as the control group. Group II were treated with L-arginine 300 mg/kg/bw. Group III were treated with α-tocopherol 30 mg/kg/bw. Group IV were treated with L-arginine and α-tocopherol. Urine and blood samples were taken at 0 (before operation), 2, 7 and 14 days post-transplantation for estimation of urine sodium, creatinine, fractional excretion of sodium, serum creatinine, sodium and blood urea nitrogen. Histological examination and measurement of malondialdehyde in kidney tissues were also performed. RESULTS: Serum creatinine and blood urea nitrogen significantly decreased in L-arginine and α-tocopherol, as well as combination groups, compared to the control group. Malondialdehyde was significantly decreased in the combination group compared to L-arginine and α-tocopherol alone. Histological examination of the control group showed that acute tubular necrosis was markedly decreased in transplanted kidneys treated with a combination of both L-arginine and α-tocopherol. CONCLUSIONS: Concomitant administration of l-arginine and α-tocopherol has a more protective effect and synergistic antioxidant effect on ischaemia/reperfusion injury in transplanted rat kidneys.


Assuntos
Arginina/administração & dosagem , Transplante de Rim , Traumatismo por Reperfusão/prevenção & controle , alfa-Tocoferol/administração & dosagem , Animais , Antioxidantes/metabolismo , Arginina/farmacologia , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Combinação de Medicamentos , Testes de Função Renal , Masculino , Malondialdeído/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , alfa-Tocoferol/farmacologia
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