ABSTRACT
The enantioselective carbenoid insertion into C(sp(3))-H bonds is an important tool for the synthesis of complex molecules due to the high control of enantioselectivity in the formation of stereogenic centers. This paper presents a brief review of the early issues, related mechanistic studies and recent applications on this chemistry area.
ABSTRACT
Lipopolysaccharide (LPS) mimics the symptoms of acute lung injury (ALI), which is characterized by the accumulation in the lungs of neutrophils producing inflammatory mediators. Because of the lack of information about phototherapy (PhT) effects on ALI, we investigated whether PhT (685nm InGaAlP) attenuates LPS-induced ALI. PhT reduced lung edema, the accumulation of TNF-alpha in the lung, and myeloperoxidase (MPO) activity. However, PhT was not efficient in reducing of TNF-alpha concentration in both serum and neutrophils of blood after LPS. In another series of experiments, in vitro assays of the effects of PhT effect on mouse pulmonary arterial endothelium cells (MPAECs) after TNF-alpha showed that the laser restores the MPAECs damage induced at 6 or 24h after TNF-alpha. These results suggest the PhT effect on ALI is partly due to inhibition of TNF-alpha release from neutrophils and lung cells.
Subject(s)
Acute Lung Injury/therapy , Phototherapy , Pneumonia/therapy , Acute Lung Injury/chemically induced , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Animals , Bronchoalveolar Lavage Fluid , Capillary Permeability , Cells, Cultured , Disease Models, Animal , Endothelial Cells/metabolism , Endothelial Cells/pathology , Escherichia coli , Lipopolysaccharides/toxicity , Lung/metabolism , Lung/pathology , Male , Mice , Peroxidase/metabolism , Pneumonia/pathology , Pulmonary Artery/metabolism , Pulmonary Artery/pathology , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/metabolismABSTRACT
OBJECTIVE: The aim of this study was to report that photodynamic therapy (PDT) with mitochondria-associated chloroaluminum phthalocyanine tetrasulfonate (AlPcS(4)) leads to significant alterations in this organelle. BACKGROUND DATA: PDT is a viable treatment modality for a variety of tumors, as well as for some non-oncologic diseases. The procedure submits cells or tissue to a photosensitizing drug followed by light irradiation of appropriate wavelength, usually in the red area or close to infrared, and compatible with the drug absorption spectrum, inducing the apoptotic process. However, the precise mechanism of PDT-induced apoptosis is not well characterized. Several cellular organelles can be postulated as the target for PDT with different photosensitizers such as plasmatic membrane, nucleus, mitochondria, endoplasmic reticulum, Golgi complex, and others. The mitochondrion is the main target in PDT because it is the main organelle involved in apoptosis. One of the main agents is cytochrome c, a proapoptotic factor that preferentially links itself to the mitochondrial cardiolipin. METHODS: The photosensitizing effects of AlPcS(4) were studied in the mitochondria. Cells were irradiated with a diode laser (670 nm, energy density of 4.5 J/cm(2), and power density of 45 mW/cm(2)). RESULTS: The fluorescent analyses of the mitochondria were performed with MitoTracker and nonyl acridine orange (NAO), and electron microscopy demonstrated that PDT with AlPcS(4) leads to significant alterations in mitochondria, causing membrane potential loss, alteration in cardiolipin distribution and cell death. CONCLUSION: The labels with Mitotracker and NAO demonstrated mitochondrial migration to the perinuclear region, confirmed through electron microscopy, suggesting that intact mitochondria were solicited for possible DNA fragmentation.
