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1.
Life Sci ; 272: 119221, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33609543

RESUMO

The present study aimed to investigate the invitro preconditioning of adipose-derived mesenchymal stem cells (ADMSCs) with CD44-targeted hyalournic acid (HA) on ischemic kidney injury in rats. Ninety male Sprague Dawley rats were randomly allocated into the following groups; i) sham group, ii) control group: rats exposed to 45 min left renal ischemia with saline treatment, iii) HA group as control group but rats treated with HA, iv) ADMSCs group as control but rats treated with ADMSCs v) HA + ADMSCs group as ADMSCs but rats treated with ADMSCs preconditioned with CD44-tageted HA for 14 days. We found that treattment with either ADMSCs or HA + ADMSCs caused significant decrease in the elevated serum creatinine and BUN and malondialdehyde (MDA) concentrations and expression of TGF-ß1, fibronectin, collagen type I, inducible nitric oxide synthease (iNOS) and microRNAs (miR-21, miR-17-5p, miR-10a) in kidney and significant increase in creatinine clearance, superoxide dismutase (SOD), reduced glutathione (GSH) and the expression of Bcl2, vascular endothelial growth factor (VEGF), Wnt/ß-catenin pathway genes in kidney compared to control group (p < 0.05). Moreover, HA + ADMSCs group caused more significant improvement in these parameters than ADMSCs group (p < 0.05), while HA group did not cause any significant improvement in these parameters compared to control group. These results suggest that preconditioning of ADMSCs preconditioned with CD44-targted HA enhanced their cytoprotective effect against ischemic kidney injury. This renoprotective effect might be due to activation of angiogenesis, Wnt/ß-catenin pathway proteins, and suppression of oxidative stress, apoptosis, inflammation and fibrosis.

2.
Life Sci ; 265: 118811, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33259867

RESUMO

AIMS: To study the effect of direct renin inhibitor (aliskiren) on the renal function during acute and chronic partial ureteral obstruction (PUO) in rat solitary kidney. MAIN METHODS: Sixty male Sprague-Dawley rats were randomly allocated into three groups (20 rats each); sham, PUO and aliskiren groups. Right nephrectomy was performed in all groups. Rats in PUO and aliskiren groups were subjected to left PUO and received no treatment and aliskiren (10 mg/kg, orally, once per day till sacrification), respectively. Blood samples were then collected for biochemical measurements. Ten rats from each group were sacrificed after two weeks, while the remaining rats were sacrificed after four weeks. Left kidneys were harvested for histopathological examination, BCL-2, interleukin (IL)-6, transforming growth factor (TGF)-ß1, collagen I and fibronectin relative gene expression and assessment of glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) activity. KEY FINDINGS: After two and four weeks of PUO, aliskiren significantly recompensed the rise of serum creatinine (Scr) and blood urea nitrogen (BUN). Aliskiren also revealed significantly better histopathological results regarding cortical and medullary necrosis, regeneration and inflammatory cell infiltration. Aliskiren group showed statistically significant up-regulation of BCL-2 and down-regulation of IL-6, TGF-ß1, collagen I and fibronectin relative gene expression. Aliskiren significantly increased GSH and SOD activity and reduced MDA and NO activity. Moreover, aliskiren administration for four weeks after PUO significantly yielded more renoprotective effect compared to its administration for two weeks. SIGNIFICANCE: Aliskiren ameliorates the deterioration of the renal function during acute and chronic PUO in a solitary kidney.

3.
Brain Sci ; 10(10)2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33096612

RESUMO

Asymptomatic valproic acid (VPA)-induced hyperammonemia in the absence of liver impairment is fairly common. However, the underlying mechanisms through which VPA causes elevation in plasma ammonia (NH4) remains under investigation. Male Sprague Dawley rats (n = 72) were randomly allocated to receive VPA 400 mg/kg, 200 mg/kg, or vehicle IP daily for either 8, 14, or 28 consecutive days. The behavioral effects of VPA were assessed. Plasma, liver, and prefrontal cortex (PFC), striatum (Str), and cerebellum (Cere) were collected 1 h post last injection and assayed for NH4 concentration and glutamine synthetase (GS) enzyme activity. Chronic VPA treatment caused attenuation of measured behavioral reflexes (p < 0.0001) and increase in plasma NH4 concentration (p < 0.0001). The liver and brain also showed significant increase in tissue NH4 concentrations (p < 0.0001 each) associated with significant reduction in GS activity (p < 0.0001 and p = 0.0003, respectively). Higher tissue NH4 concentrations correlated with reduced GS activity in the liver (r = -0.447, p = 0.0007) but not in the brain (r = -0.058, p = 0.4). Within the brain, even though NH4 concentrations increased in the PFC (p = 0.001), Str (p < 0.0001), and Cere (p = 0.01), GS activity was reduced only in the PFC (p < 0.001) and not in Str (p = 0.2) or Cere (p = 0.1). These results suggest that VPA-induced elevation in plasma NH4 concentration could be related, at least in part, to the suppression of GS activity in liver and brain tissues. However, even though GS is the primary mechanism in brain NH4 clearance, the suppression of brain GS does not seem to be the main factor in explaining the elevation in brain NH4 concentration. Further research is urgently needed to investigate brain NH4 dynamics under chronic VPA treatment and whether VPA clinical efficacy in treating seizure disorders and bipolar mania is impacted by its effect on GS activity or other NH4 metabolizing enzymes.

4.
Heliyon ; 6(10): e05192, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33083625

RESUMO

Objectives: Pomegranate juice (PJ) is rich in important compounds with anti-cancer activities. This study aims to investigate the preventive effect of pomegranate juice (PJ) against bladder cancer (BC). Methods: Eighty male Sprague Dawley rats were randomly classified into 4 equal groups: (1) Normal controls; (2) PJ group: supplied by PJ for 12 weeks; (3) Cancer-induced group: intake 0.05% v/v N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for 8 weeks; (4) Cancer-prevented group: BBN + PJ. After 12 weeks, all rats were sacrificed and their urinary bladder tissues were subjected to histopathological and immunohistochemical (p53) examinations, expression of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), hypoxia-inducible factor 1 (HIF-1) and the tumor protein p53 (TP53) and analysis of oxidative stress markers. Results: The development of BC was: 0/20 (0%) in normal, PJ and cancer-prevented groups and 20/20 (100%) in cancer-induced group. Significant neoplastic lesions were observed in cancer-induced group. Mild preneoplastic alterations were noticed in 25% (5/20) of cancer-prevented group. p53 immunostaining were significantly elevated in the cancer-induced group, which was decreased in the cancer-prevented group. The relative expressions of IL-6, TNF-α, HIF-1 and TP53 were significantly lower in the cancer-prevented group compared to the cancer-treated group. Correction in the oxidative stress markers were also observed in the cancer-prevented group. Conclusion: PJ possesses a promising inhibitory effect on BC development, probably due to its anti-oxidant and anti-inflammatory properties.

5.
Neurourol Urodyn ; 39(8): 2447-2454, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32960981

RESUMO

PURPOSE: To study the effect of intravesical instillation of botulinum neurotoxin-A (BoNT-A) combined with low energy shock wave (LESW) for treatment of overactive bladder (OAB) in a rat model and to investigate its effect on the associated inflammatory and oxidative stress process. MATERIAL AND METHODS: Forty rats were subdivided into four equal groups: normal control group, OAB group, LESW group, and BoNT-A plus LESW group. Cystometrogram (CMG) changes and histopathological changes in the bladder mucosa were assessed in the different groups. Oxidative stress markers (malondialdehyde [MDA] and superoxide dismutase [SOD]) and proinflammatory cytokines (tumor necrotic factor-α [TNF-α] and interleukin-6 [IL-6]) were compared among groups. RESULTS: BoNT-A plus LESW group showed statistically significant lower amplitude (p = .001) and lower frequency of detrusor contractions (p = .01) compared to LESW, which showed no statistically significant difference in comparison to the OAB group. Also, the combined group significantly reduced submucosal edema and inflammatory cell infiltrate scores compared to all groups (p < .05). LESW was associated with 42% reduction of MDA expression while, LESW plus BoNT-A decreased it by 68% (p < .001). Also, LESW and LESW plus BoNT-A increased SOD expression by 43% and 75%, respectively (p < .001). LESW plus BoNT-A was associated with statistically significant lower expression of TNF-α and IL-6 expression by 37% and 66% in comparison to LESW group (p = .001). CONCLUSION: Intravesical instillation of BoNT-A plus LESW is an effective method for increasing the urothelial permeability to BoNT-A and enhancing its therapeutic effect against OAB in rat model through the expression of a substantial anti-inflammatory and antioxidative stress effect.

6.
Life Sci ; 258: 118242, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32784056

RESUMO

AIMS: As the spermatogenesis process is targeted by cisplatin (Cis) that changes testicular morphology, alters sperm quality, and hence causes male infertility. This study investigated the possible therapeutic effects of l-carnitine (LC) on Cis impaired spermatogenesis's establishment during the prepubertal phase. MATERIALS AND METHODS: Ninety-six prepubertal Sprague Dawley male rats were divided into four groups. CONTROL GROUP: rats were injected with 0.9% saline solution intraperitoneally (i.p.). LC group: animals were injected for eight weeks, with 250 mg/kg/wk. LC (i.p.). Cis group: animals were injected with a single dose of 5 mg/kg Cis (i.p.). LC + Cis group: animals were pre-injected with LC 250 mg/kg 2 h before Cis injection. The rats were sacrificed at 37, 60, and 90 days old, and their testes were taken for biochemical, molecular, and histopathological studies. The motility, viability, morphology, and DNA fragmentation of sperm in adult rats were also measured. KEY FINDINGS: Group treated with LC and Cis showed an increase in antioxidant and hormonal activity compared to the Cis treated group in the pre and post-pubertal period. Moreover, there was an increase in sperm survival, motility, and DNA integrity. Furthermore, LC showed an increase in the anti-apoptotic and chromatin remodeling genes and a decrease in the pro-inflammatory genes. SIGNIFICANCE: LC could enhance the spermatogenesis process after exposure to Cis during the prepubertal phase by restoring the balance between reactive oxygen species and antioxidant activity, improving hormonal activity, sperm quality and DNA integrity, promoting protamination and blood-testis barrier integrity, and maintaining the testicular architecture.


Assuntos
Carnitina/farmacologia , Cisplatino/toxicidade , Infertilidade Masculina/prevenção & controle , Infertilidade Masculina/fisiopatologia , Maturidade Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Animais , Antineoplásicos/toxicidade , Carnitina/uso terapêutico , Infertilidade Masculina/induzido quimicamente , Masculino , Ratos , Ratos Sprague-Dawley , Maturidade Sexual/fisiologia , Motilidade Espermática/efeitos dos fármacos , Motilidade Espermática/fisiologia , Espermatogênese/fisiologia
7.
Urol Oncol ; 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32800441

RESUMO

OBJECTIVES: To assess the clinical performance characteristics of Xpert Monitor test for recurrence detection during surveillance of patients with non muscle invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Patient with previous history of NMIBC were included in the study. Voided urine specimens were collected for Xpert monitor analysis and cytology. Office cystoscopy was performed for all study participants with in patient biopsy specimen retrieval for positive or suspicious cases. Test characteristics were calculated based on cystoscopy/biopsy results and compared between Xpert and cytology. RESULTS: Between March 2018 and May 2019, 181 patients including 168 (92.8%) males fulfilled the study criteria with median age 61 years, Primary tumors were low, intermediate, high risk in 2.8%, 22.7% and 74.5% of patients respectively. Biopsy proven recurrence was detected in 19 patients (10.4%). Xpert Monitor had a sensitivity of 73.7% with a negative predictive value (NPV) of 96.3%. Xpert Monitor was positive in all cases with high grade tumors (9 patients). Urine cytology showed sensitivity of 47% and an NPV of 93.2%. During follow up surveillance, out of 162 cystoscopy negative patients (CNP), 9.3% developed recurrence within 8 months. Xpert Monitor was found to be an independent predictor of early recurrence in CNP (HR=2.8, 95%CI=1.1-7.2, p=0.01). CONCLUSIONS: Xpert Monitor urine test has a superior diagnostic performance for recurrence detection in NMIBC patients compared to urine cytology. It might be a helpful tool not only for excluding bladder cancer recurrence in those patients, but also for prediction of possible future early recurrence.

8.
BJU Int ; 2020 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-32654305

RESUMO

OBJECTIVES: To study the efficacy of low-energy shock wave therapy (LESW) on enhancing intravesical epirubicin (EPI) delivery in a rat model of bladder cancer (BCa). MATERIALS AND METHODS: A total of 100 female Fischer rats were randomly allocated into five groups: control; BCa; LESW; EPI; and EPI plus LESW. After BCa induction by N-butyl-N-(4-hydroxybutyl)nitrosamine, EPI (0.6 mg/0.3 mL of EPI diluted in 0.3 mL saline) or saline (0.6 mL) was administered and retained in the bladders for 1 h with or without LESW treatment (300 pulses at 0.12 mJ/mm2 ). This was repeated weekly for 6 weeks. Survival was then calculated, rats were weighed and their bladders were harvested for bladder/body ratio estimation, histopathological examination, p53 immunostaining, miR-210, hypoxia-inducible factor (HIF)-1α, tumour necrosis factor (TNF)-α and interleukin (IL)-6 relative gene expression and fluorescence spectrophotometric drug quantification. Heart and blood samples were also collected for assessment of the safety profile and toxicity. RESULTS: The EPI plus LESW group had significantly lower mortality rates, loss of body weight and bladder/body ratio. Histopathological results in terms of grossly visible bladder lesions, mucosal thickness, dysplasia formation and tumour invasion were significantly better in the combined treatment group. The EPI plus LESW group also had statistically significant lower expression levels of p53 , miR-210, HIF-1α, TNF-α and IL-6. LESW increased urothelial concentration of EPI by 5.7-fold (P < 0.001). No laboratory variable exceeded the reference ranges in any of the groups. There was an improvement of the indicators of EPI-induced cardiomyopathy in terms of congestion, hyalinization and microvesicular steatosis of cardiomyocytes (P = 0.068, 0.003 and 0.046, respectively) in the EPI plus LESW group. CONCLUSIONS: The combined use of intravesical EPI and LESW results in less BCa invasion and less dysplasia formation, as LESW increases urothelial permeability of EPI and enhances its delivery into tumour tissues, without subsequent toxicity.

9.
Environ Sci Pollut Res Int ; 27(13): 15835-15841, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32095963

RESUMO

To evaluate Cu and Zn levels in bladder cancer (BC) patients and their relationship with expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1). Plasma levels of Cu and Zn were determined in 66 transitional bladder cell carcinoma patients (BC group) and 60 matched controls. The concentration of Cu and Zn as well as the expressions of both VEGF and HIF-1 were also estimated in cancerous and non-cancerous bladder tissues in the BC group. The results showed that plasma Cu and Cu/Zn ratio were significantly higher in BC group when compared with the control group. In contrast, the plasma Zn in BC group was significantly lower than in the controls. Comparing levels of Cu and Zn in cancerous and non-cancerous bladder tissues among the BC group indicated a significantly higher Cu levels in the cancerous tissues, while Zn levels was significantly lower. There were higher expressions of both VEGF and HIF-1 in the cancerous samples. Moreover, the Cu concentration in cancerous tissues was significantly correlated with expressions of VEGF and HIF-1. Logistic regression analysis revealed that the increase in plasma Cu/Zn ratio and plasma Cu and the decrease in plasma Zn may be risk factors for development of bladder cancer. We concluded that alteration of plasma and bladder tissue levels of both Cu and Zn is correlated with pathogenesis of bladder cancer. The increase in Cu level in cancerous tissues of BC group has an important role in angiogenesis in bladder cancer cells.


Assuntos
Neoplasias da Bexiga Urinária , Cobre , Humanos , Fator 1 Induzível por Hipóxia , Fator A de Crescimento do Endotélio Vascular , Zinco
10.
Urol Oncol ; 38(4): 278-285, 2020 04.
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.

11.
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.

12.
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
13.
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
14.
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
15.
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
16.
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
17.
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.

18.
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
19.
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
20.
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.

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