RESUMEN
Exposure of human immune cells to asbestos causes a reduction in antitumor immunity. The present study aimed to investigate the recovery of reduced antitumor immunity by several ingredients taken as supplements or foods, including trehalose (Treh) and glycosylated hesperidin (gHesp). Peripheral blood CD4+ cells were stimulated with IL2, antiCD3 and antiCD28 antibodies for 3 days, followed by further stimulation with IL2 for 7 days. Subsequently, cells were stimulated with IL2 for an additional 28 days. During the 28 days, cells were cultured in the absence or presence of 50 µg/ml chrysotile asbestos fibers. In addition, cells were treated with 10 mM Treh or 10 µM gHesp. Following culture for 28 days, reverse transcriptionquantitative PCR was performed to assess the expression levels of transcription factors, cytokines and specific genes, including matrix metalloproteinase7 (MMP7), nicotinamide nucleotide transhydrogenase (NNT) and CXC motif chemokine receptor 3, in unstimulated cells (fresh) and cells stimulated with PMA and ionomycin (stimuli). The results demonstrated that compared with the control group, chrysotileexposure induced alterations in MMP7, NNT and IL17A expression levels were not observed in the 'Treh' and 'gHesp' groups in stimulated cells. The results suggested that Treh and gHesp may reverse asbestos exposureinduced reduced antitumor immunity in T helper cells. However, further investigation is required to confirm the efficacy of future trials involving the use of these compounds with highrisk human populations exposed to asbestos, such as workers involved in asbestoshandling activities.
Asunto(s)
Amianto/efectos adversos , Linfocitos T CD4-Positivos/inmunología , Suplementos Dietéticos , Hesperidina/farmacología , Mesotelioma Maligno/inmunología , Trehalosa/farmacología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Células Cultivadas , Humanos , Interferón gamma/inmunología , Interleucina-17/inmunología , Masculino , Mesotelioma Maligno/inducido químicamente , Mesotelioma Maligno/prevención & control , Persona de Mediana Edad , Receptores CXCR3/inmunologíaRESUMEN
Beta-amyloid (Aß) peptides are considered to play a major role in the pathogenesis of Alzheimer's disease (AD) and molecules that can prevent pathways of Aß toxicity may be potential therapeutic agents for treatment of AD. We have previously reported that NK-4, a cyanine photosensitizing dye, displays neurotrophic and antioxidant activities. In this study, we report the effects of NK-4 on the toxicity of Aß and on cognitive function and Aß concentration in a transgenic mouse model of AD (Tg2576). In vitro, NK-4 effectively protected neuronal cells from toxicity induced by Aß. In addition, it displayed profound inhibitory activities on Aß fibril formation. In vivo, Tg2576 mice received an intraperitoneal injection at 100 or 500 µg/kg of NK-4 once a day, five times a week for 9 months. Administration of NK-4 to the mice attenuated impairment of recognition memory, associative memory, and learning ability, as assessed by a novel object recognition test, a passive avoidance test, and a water maze test, respectively. NK-4 decreased the brain Aß concentration while increasing the plasma amyloid level in a dose-dependent manner. NK-4 also improved memory impairments of ICR mice induced by direct intracerebroventricular administration of Aß. These lines of evidence suggest that NK-4 may affect multiple pathways of amyloid pathogenesis and could be useful for treatment of AD.
Asunto(s)
Enfermedad de Alzheimer/patología , Fármacos Fotosensibilizantes/farmacología , Quinolinas/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/psicología , Animales , Carbocianinas , Fármacos del Sistema Nervioso Central/farmacología , Fármacos del Sistema Nervioso Central/uso terapéutico , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos ICR , Ratones Transgénicos , Células PC12 , Fármacos Fotosensibilizantes/uso terapéutico , Quinolinas/uso terapéutico , Ratas , Reconocimiento en Psicología/efectos de los fármacos , Reconocimiento en Psicología/fisiología , Natación/fisiología , Natación/psicologíaRESUMEN
We previously studied antioxidant profiles in the plasma of hibernating Syrian hamsters and found a transient increase of a superoxide radical-scavenging activity during the arousal phase. In this report, we purified and identified the high molecular weight superoxide dismutase (SOD)-like factor from the plasma of arousing hamsters. The cyanide-sensitive 240 kDa SOD-like factor showed a significant homology to mammalian extracellular SOD (EC-SOD) reported, although the molecular mass of EC-SOD was 135 kDa. The cDNA cloning revealed that the 240 kDa SOD-like factor was identical to the hamster ortholog of EC-SOD. It consisted of 245 amino acid residues including a signal sequence of 20 amino acid residues. Five cysteine residues that would participate in inner- and inter-subunit bonds were well conserved among species. Interestingly, there were four potential N-glycosylation sites in hamster EC-SOD, whereas there is only one site in other species. The amino acid sequence analysis indicated that three of the four sites were modified. These results suggest that the anomalistically high molecular weight of hamster EC-SOD is ascribed, at least in part, to the addition of extra sugar chains. Furthermore, results obtained here also propose the involvement of EC-SOD in the antioxidative defense of hibernating hamsters.