RESUMO
In hypertensive animals and patients, oxidative stress represents the primary risk factor for progression of renal disease. Recently, it has been demonstrated that hydrogen, as a novel antioxidant, can selectively reduce hydroxyl radicals and peroxynitrite anion to exert therapeutic antioxidant activity. Herein, we investigated the protective effect of hydrogen-rich water (HW) against renal injury in spontaneously hypertensive rats (SHR). The 8-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into HW-treated (1.3 ± 0.2 mg/l for 3 months, drinking) and vehicle-treated group. Although treatment with HW had no significant effect on blood pressure, it significantly ameliorated renal injury in SHR. Treatment with HW lowered reactive oxygen species formation, upregulated the activities of superoxide dismutase, glutathione peroxidase, glutathione-S-epoxide transferase, and catalase, and suppressed NADPH oxidase activity. Treatment with HW in SHR depressed pro-inflammatory cytokines expression including TNF-α, IL-6, IL-1ß, and macrophage chemoattractant protein 1, which might be mediated by suppressing nuclear factor-κB activation. In addition, treatment with HW had protective effect on mitochondrial function including adenosine triphosphate formation and membrane integrity in SHR. In conclusion, consumption of HW is a promising strategy to alleviate renal injury as a supplement for anti-hypertensive therapy.
Assuntos
Água Potável/química , Hidrogênio/análise , Rim/lesões , Animais , Sequência de Bases , Pressão Sanguínea , Quimiocina CCL2/sangue , Citocinas/sangue , Primers do DNA , Rim/metabolismo , Rim/fisiopatologia , Masculino , Mitocôndrias/fisiologia , NADPH Oxidases/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
PURPOSE: High-grade bleeding is a serious adverse event associated with bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor and widely used in the current cancer treatments. The aim of this study was to gain a better understanding of the overall incidence and risk of high-grade bleeding in cancer patients who receive bevacizumab therapy. METHODS: We performed a meta-analysis of relevant randomized controlled trials (RCTs) identified in PubMed, Cochrane library, Embase, and American Society of Clinical Oncology conferences. Overall relative risks (RRs), incidence rates, and 95% confidence intervals (CIs) were calculated using a random-effects model. The primary clinical endpoint was high-grade bleeding (grade 3 or above). RESULTS: A total of 14,277 patients with a variety of solid tumors from 22 RCTs were included in the present analysis. The addition of bevacizumab to cancer chemotherapy significantly increased the risk of high-grade bleeding (RR 1.60, 95% CI 1.19-2.15), with RRs of high-grade bleeding among patients receiving bevacizumab at 2.5 and 5 mg/kg per week of 1.27 (95% CI 0.95-1.71) and 3.02 (95% CI 1.85-4.95), respectively. The overall incidence of high-grade bleeding among patients receiving bevacizumab was 2.8% (95% CI 2.1-3.8). Higher risks were observed in patients with non-small-cell lung cancer (RR 3.41, 95% CI 1.68-6.91), renal cell carcinoma (RR 6.37, 95% CI 1.43-28.33), and colorectal cancer (RR 9.11, 95% CI 1.70-48.79) who were receiving bevacizumab at 5 mg/kg per week. CONCLUSIONS: Among the patients included in the trials analyzed in this meta-analysis, the addition of bevacizumab to cancer chemotherapy significantly increased the risk of high-grade bleeding. The risk may be dose-dependent and may vary with tumor type.
Assuntos
Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Hemorragia/epidemiologia , Neoplasias/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Bevacizumab , Relação Dose-Resposta a Droga , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Humanos , Incidência , Neoplasias/epidemiologia , Risco , Fatores de Risco , Fator A de Crescimento do Endotélio VascularRESUMO
Baicalein, a naturally occurring flavone, has been proved as a promising chemopreventive compound for many chronic human diseases. The aim of this work was to investigate whether treatment with baicalein prevented nonalcoholic steatohepatitis (NASH) induced by methionine-choline-deficient (MCD) diet. Rats were divided into four experimental groups and fed for 8 weeks as follows: (1) control rats; (2) control rats treated with baicalein (intraperitoneal injection of 10mg/kg); (3) MCD-diet-fed rats; (4) MCD-diet-fed rats treated with baicalein. Treatment with baicalein prevented MCD-diet-induced NASH, as evidenced by reduced histological scores, apoptosis, activities of ALT and AST, and hepatic fat accumulation in rats. Treatment with baicalein abated MCD-diet-induced oxidative stress through enhancing Nrf2/HO-1 pathway and activities of SOD and catalase in livers. Treatment with baicalein preserved hepatic mitochondrial function in MCD-diet fed rats. Treatment with baicalein reduced hepatic NO formation through suppressing MCD-diet-induced iNOS activation, and suppressed MCD-diet-induced inflammation through suppressing NFκB activation and reducing IL-6 and TNFα expressions in livers. Treatment of MCD-diet fed rats with baicalein had a beneficial modulation on expression profiles of fatty acid metabolism genes in livers. The results support the investigation of baicalein as a therapeutic candidate for NASH induced by MCD diet in rats.
Assuntos
Colina/análise , Dieta , Fígado Gorduroso Alcoólico/tratamento farmacológico , Fígado Gorduroso Alcoólico/etiologia , Flavanonas/farmacologia , Metionina/análise , Animais , Ácidos Graxos/metabolismo , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/patologia , Flavanonas/uso terapêutico , Masculino , Mitocôndrias/efeitos dos fármacos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Estresse Oxidativo/efeitos dos fármacos , RatosRESUMO
Myeloid sarcoma (MS) is a neoplasm of immature granulocytes, monocytes, or both involving extramedullary sites. MS with no evidence of leukemia (nonleukemic MS) is very rare and the initial diagnosis can be difficult. This report describes an unusual case of nonleukemic MS of the liver in a 16-year-old patient presenting as debilitating hepatomegaly. A liver biopsy revealed diffuse infiltration by neoplastic cells of myeloid lineage (CD68, myeloperoxidase). A bone marrow biopsy showed no evidence of medullary involvement. The patient subsequently developed heart failure. Autopsy revealed infiltration of most organs by neoplastic cells but failed to identify abnormal myeloid cells in bone marrow.