RESUMO
Dopamine (DA) is commonly used to maintain the hemodynamic stability of brain-dead donors despite its controversial effects on organ functions. This study aimed at examining the hemodynamic effect of DA in a rat brain-dead model in vivo, alteration of hepatocyte integrity in liver grafts after ex vivo preservation, and changes in cultured clone-9 hepatocytes including cellular viability, cell cycle, apoptotic regulators, and lipopolysaccharide (LPS)-stimulated nuclear factor kappa B (NF-κB) signaling machinery. Although in vivo findings demonstrated enhanced portal venous blood flow and hepatic microcirculatory perfusion after DA infusion, no apparent advantage was noted in preserving hepatocyte integrity ex vivo. In vitro, prolonged exposure to high-dose DA reduced proliferation and induced G1 growth arrest of clone-9 hepatocytes with concomitant decreases in B cell lymphoma 2 (BCL2)/B cell lymphoma 2-associated X protein (BAX) and heat shock protein 70/BAX protein ratios and intracellular NF-κB p65. Moreover, DA pretreatment suppressed LPS-elicited inhibitor of κBα phosphorylation and subsequent NF-κB nuclear translocation, suggesting that DA may down-regulate NF-κB signaling, thereby reducing expression of antiapoptotic regulators, such as BCL2. In conclusion, despite augmentation of hepatic perfusion, DA infusion failed to preserve hepatocyte integrity both in vivo and ex vivo. In vitro findings demonstrated that high-dose DA may hamper the function of NF-κB signaling machinery and eventually undermine functional integrity of hepatocytes in liver grafts.
Assuntos
Cardiotônicos/farmacologia , Dopamina/farmacologia , Hepatócitos/efeitos dos fármacos , NF-kappa B/metabolismo , Animais , Apoptose , Células Cultivadas , Hepatócitos/metabolismo , Técnicas In Vitro , Lipopolissacarídeos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Circulação Hepática , Masculino , Preservação de Órgãos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-DawleyRESUMO
Ceramic materials with biological effects (bioceramic) have been found to modulate various biological effects, especially those effects involved in antioxidant activity and hydrogen peroxide scavenging. As arthropathy and osteopathy are the major chronic diseases of geriatric medicine, we explored the possible activity of bioceramic on these conditions using animal and cell models. Rabbits received intra-articular injections of lipopolysaccharides (LPS) to induce inflammation that mimic rheumatic arthritis. FDG isotopes were then IV injected for PET scan examinations at 16 hours and 7 days after the LPS injection. We examined and compared the bioceramic and control groups to see if bioceramic was capable of relieving inflammation in the joints by subtracting the final and initial uptake amount of FDG (max SUV). We studied the effects in prostaglandin E2 (PGE2) inhibition on the human chondrosarcoma (SW1353) cell line, and the effects on the murine osteoblast (MC3T3-E1) cell line under oxidative stress. All the subtractions between final and initial uptakes of FDG in the left knee joints of the rabbits after LPS injection indicated larger decreases in the bioceramic group than in the control group. This anti-arthritic or inflammatory effect was also demonstrated by the PGE2 inhibition of the SW1353 cells. We further proved that bioceramic treatment of the MC3T3-E1 cells resulted in increased viability of osteoblast cells challenged with hydrogen peroxide toxicity, and increased alkaline phosphatase activity and the total protein production of MC3T3-E1 cells under oxidative stress. Since LPS-induced arthritis is an experimental model that mimics RA, the potential therapeutic effects of bioceramic on arthropathy merit discussion. Bioceramic may contribute to relieving inflammatory arthritis and maintaining bone health.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Cerâmica/uso terapêutico , Osteoblastos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Osso e Ossos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cerâmica/farmacologia , Condrossarcoma/metabolismo , Dinoprostona/metabolismo , Avaliação Pré-Clínica de Medicamentos , Humanos , Peróxido de Hidrogênio , Articulações/efeitos dos fármacos , Lipopolissacarídeos , Masculino , Osteoblastos/citologia , Osteoblastos/enzimologia , Tomografia por Emissão de Pósitrons , Coelhos , Distribuição AleatóriaRESUMO
An enhanced electrokinetic (EK) remediation process coupled with permeable reaction barrier (PRB) of carbon nanotube coated with cobalt (CNT-Co) has been investigated for As(V) removal from soil under potential gradient of 2.0 V/cm for 5 days treatment. Results showed that removal efficiency of As(V) was greater than 70% in EK/CNT-Co system with EDTA as processing fluid, which was enhanced by a factor of 2.2 compared to EK system and EK/CNT systems. A better removal performance in EK/CNT-Co system was attributed to higher sorption of As(V) onto CNT-Co than onto CNT. Removal of As(V) in EK/CNT-Co system was mainly contributed by surface sorption on CNT-Co rather than by EK process. The surface characteristics of CNT-Co, which was qualified by SEM coupled with EDS, were clearly confirmed that arsenic was adsorbed on the passive layer surface. Among EK processes, As(V) removal was dominated by electroosmosis flow and electromigration in EK/CNT-Co system with groundwater and EDTA as processing fluid. An investigation with sequential extraction revealed that As(V) associated with soils was considerably shifted from strong binding forms, i.e., Fe-Mn oxide, organic, and residual, to weak binding forms, i.e., exchange and carbonate, after EK/CNT-Co treatment.