RESUMO
Oxidative stress is a pathophysiological condition resulting in neurotoxicity, which is possibly associated with neurodegenerative disorders. In this study, the antioxidative effects of the antioxidant astaxanthin (AXT) in combination with huperzine A (HupA), which is used as a cholinesterase inhibitor for the treatment of Alzheimer's disease, were investigated. PC12 cells were treated with either tertbutyl hydroperoxide (TBHP), or with the toxic version of ßamyloid, Aß2535, to induce oxidative stress and neurotoxicity. Cell viability, morphology, lactate dehydrogenase (LDH) release, intracellular accumulation of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were determined, while neuroprotection was also monitored using an MTT assay. It was found that combining AXT with HupA significantly increased the viability of PC12 cells, prevented membrane damage (as measured by LDH release), attenuated intracellular ROS formation, increased SOD activity and decreased the level of MDA after TBHP exposure when compared to these drugs administered alone. Pretreatment with HupA and AXT decreased toxic damage produced by Aß2535. These data indicated that combining an antioxidant with a cholinesterase inhibitor increases the degree of neuroprotection; with future investigation this could be a potential therapy used to decrease neurotoxicity in the brain.
Assuntos
Alcaloides/farmacologia , Doença de Alzheimer/tratamento farmacológico , Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Fármacos Neuroprotetores/farmacologia , Sesquiterpenos/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Xantofilas/farmacologiaRESUMO
Immunohistochemical studies have revealed that cystatin C (CysC) co-localizes with amyloid-ß (Αß) in amyloid-laden vascular walls and in the senile plaque cores of amyloid. In vitro and in vivo animal studies suggest that CysC protects against neurodegeneration by inhibition of cysteine proteases, inhibition of Αß aggregation, induction of autophagy and induction of cell division. CysC levels may be altered and may have a potential link with cerebrospinal fluid (CSF) Aß levels in various types of dementia with characteristic amyloid deposits, such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and the atrophic form of general paresis (AF-GP). We assessed the serum and CSF levels of CysC and the CSF levels of Aß40 and Aß42 in patients with AD (nâ=â51), DLB (nâ=â26) and AF-GP (nâ=â43) and normal controls (nâ=â30). Using these samples, we explored the correlation between CSF CysC and CSF Aß levels. We found that in comparison to the normal control group, both CSF CysC and CSF Aß42 levels were significantly lower in all three dementia groups (all p<0.001); serum CysC levels were the same in the AD and DLB groups, and were lower in the AF-GP group (pâ=â0.008). The CSF CysC levels were positively correlated with both the CSF Aß40 and Aß42 levels in the AD, AF-GP and normal control groups (râ=â0.306â¼0.657, all p<0.05). Lower CSF CysC levels might be a common feature in dementia with characteristic amyloid deposits. Our results provide evidence for the potential role of CysC involvement in Aß metabolism and suggest that modulation of the CysC level in the brain might produce a disease-modifying effect in dementia with characteristic amyloid deposits.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Cistatina C/líquido cefalorraquidiano , Doença por Corpos de Lewy/líquido cefalorraquidiano , Neurossífilis/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Creatina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular/fisiologia , Humanos , Imuno-Histoquímica , Estatísticas não ParamétricasRESUMO
AIM: To study the clinical significance of determination of serum B7-H4 in patients with malignant hematologic diseases. METHODS: Serum B7-H4 levels were determined in 65 patients with leucemia, 34 patients with lymphoma, 12 patients with multiple myeloma as well as in 50 healthy controls. RESULTS: The serum B7-H4 levels in patients with lymphoma [(38.81+/-10.34) kappag/L] were significantly higher than healthy controls [(31.62+/-9.850) kappag/L] (P<0.01). But there are no significant difference of B7-H4 levels in serum among patients with leucemia, patients with multiple myeloma and healthy controls. CONCLUSION: These results suggest that the B7-H4 may correlated with lymphoma, but uncorrelated with leucemia and multiple myeloma. Measurement of serum B7-H4 level provide useful information for distinctive diagnosis of different kinds of malignant hematologic diseases.
Assuntos
Antígeno B7-1/sangue , Doenças Hematológicas/sangue , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Leucemia/sangue , Linfoma/sangue , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Adulto JovemRESUMO
Previous studies demonstrate that both membrane B7-H4 and B7-H4-Ig fusion protein could inhibit T-cell responses. In the present study, we explored the potential effect of B7-H4-Ig on liver injury in a hepatitis mouse model induced by concanavalin A (ConA). A B7-H4-Ig construct was introduced into animals by the hydrodynamic gene delivery approach. It was found that ectopic expression of B7-H4-Ig could inhibit ConA-induced elevation of serum levels of ALT and AST, suppress liver necrosis and even mortality of mice. Furthermore, we observed that pretreatment of B7-H4-Ig dramatically decreased serum levels and the expression of mRNA for IL-2, IFN-gamma and IL-4, but increased IL-10 in ConA-treated mice. Our results suggest that B7-H4-Ig may protect animals from liver injury induced by ConA, which could be associated with reduced serum levels for IL-2, IFN-gamma and IL-4 as well as enhanced IL-10 production.