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Int Urol Nephrol ; 48(2): 287-97, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26660954


OBJECTIVES: To study the effects of darbepoetin-α (DPO-α) (erythropoietin analog) on adriamycin (ADR)-induced chronic nephropathy in rats. METHODS: Sixty-nine male Sprague-Dawley rats divided into 3 groups (23 rats each): negative control group: normal rats received saline as a vehicle; positive control (ADR) group: rats received 2 iv injection of ADR via penile vein at 14-day interval without treatment; and DPO-α group: as ADR group but rats received sc DPO-α (0.3 µg/kg bw) once weekly for 12 weeks. By the end of experiment hemoglobin (Hb) content, serum creatinine, BUN, albumin, triglycerides and cholesterol, urinary protein excretion and kidney injury molecule-1 (KIM-1). GSH, malondialdehyde, caspase-3 expression histopathological and electron microscopic examinations for kidney tissues were done. RESULTS: DPO-α significantly improved the animal survival rate and body weight, Hb, serum BUN, triglycerides, cholesterol, and albumin and urinary protein excretion and KIM-1 in urine. Also, administration of DPO-α improved the morphological damage in glomeruli and renal tubules as well as caspase-3 expression and markers of oxidative stress in kidney tissues. CONCLUSION: Administration of DPO-α alleviates ADR nephropathy and this might due to improvement of Hb content, hyperlipidemia, enhancement of endogenous antioxidants, reduction of apoptosis and tubulointerstitial injury and maintaining the integrity of glomerular membrane.

Darbepoetina alfa/administração & dosagem , Glomérulos Renais/ultraestrutura , Túbulos Renais/ultraestrutura , Insuficiência Renal Crônica/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Modelos Animais de Doenças , Doxorrubicina/toxicidade , Hematínicos/administração & dosagem , Glomérulos Renais/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Peroxidação de Lipídeos , Masculino , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia
BJU Int ; 107(2): 323-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20346036


OBJECTIVE: To investigate effects of combination of erythropoietin (EPO) and epidermal growth factor (EGF) on renal ischaemia and on reactive oxygen species in a rat model. MATERIALS AND METHODS: In all, 90 male Sprague-Dawley rats were allocated into five groups of 18, designated: Sham; treated with right nephrectomy only; Control, subjected to left renal ischaemia for 45 min with no treatment; EPO-treated, as the control but with EPO pretreatment; EGF-treated, as the control but with EGF pretreatment; EPO + EGF-treated, as the control but with EPO and EGF pretreatment. Renal function, histopathology and malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) levels in kidneys were assessed at 1, 2 and 7 days after ischaemia. RESULTS: All rats except the controls had a significant improvement in serum creatinine, creatinine clearance and fractional excretion of Na(+) ; all three were significantly better in EPO + EGF group than in all other groups Histopathological examination showed marked structural damage in control rats. The tubular damage was least in the EPO + EGF group. The control group had a significant increase in MDA level and a significant decrease in SOD and GSH, while the EPO + EGF group had a marked significant reduction in MDA and increase in GSH and SOD. CONCLUSION: The protection against ischaemia/reperfusion injury might be maximal when EPO and EGF are administered concomitantly, and their protective effect might be partly due to their antioxidant effects.

Antioxidantes/uso terapêutico , Fator de Crescimento Epidérmico/uso terapêutico , Eritropoetina/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Análise de Variância , Animais , Quimioterapia Combinada , Rim/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia
J Egypt Natl Canc Inst ; 22(1): 87-94, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21503011


BACKGROUND AND OBJECTIVE: Bcl-2 family members can be functionally divided into anti-apoptotic and proapoptotic groups. The balance between these two groups may determine the fate of tumor cells. In hepatocellular carcinoma (HCC), this balance is often tilted towards the anti-apoptotic members in tumor cells, leading to resistance to cell death and rapid proliferation. MATERIAL AND METHODS: In the current study, we investigated Bcl-2 and proliferating cell nuclear antigen (PCNA) immunohistochemically, using specific monoclonal antibodies in liver tissues obtained from two patient groups. The first group included fifty patients infected with hepatitis C virus (HCV) without hepatocellular carcinoma, the other group included twenty five HCVinfected patients but with confirmed HCC. Serum Bcl-2 was assayed using enzyme immunoassay. RESULTS: Results showed serum Bcl-2 was elevated in 82% versus 100% in HCC-free and HCC patients, respectively. Moreover, cytoplasmic staining of Bcl-2 was found in only 16% of chronic HCV patients without HCC, versus 8% in HCC patients. On the other hand, nuclear staining of PCNA was detected in 100% of HCC patients, but in none of the HCV patients without HCC. CONCLUSION: The results collectively suggest that in HCV-infected patients with and without HCC, apoptosis is dysregulated and proliferation activity perturbed. There may be prognostic and/or diagnostic potential in estimating Bcl-2 and PCNA proteins in these patient groups. KEY WORDS: Bcl-2 - PCNA - Apoptosis - HCC - HCV.