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Results for “Chlorophyllides”

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At least 505 records · Page 28Linked to original sources
PubMed1983

Immunopharmacological studies of sodium copper chlorphyllin (SCC).

Effect of sodium copper chlorophyllin (SCC) on experimental allergic reaction was investigated. IgE antibody mediated reactions, homologous passive cutaneous anaphylaxis (PCA) in rats and the release of anaphylactic mediators (histamine and/or slow reacting substance of anaphylaxis (SRS-A] from sensitized guinea pig lung tissues or rat peritoneal mast cells classified as a Type I reaction were clearly inhibited by SCC at a similar potency as N-(3',4'-dimethoxy cinnamoyl) anthranilic acid (N-5'). The increase of vascular permeability in rat skin caused by autacoids or enzymes that participate in the Type I reaction was also inhibited by SCC. Type II or III, complement dependent, reactions including reversed cutaneous anaphylaxis (RCA) in rats and Forssman cutaneous vasculitis (FCV) in guinea pigs were inhibited by SCC. Prednisolone inhibited RCA in rats, but did not inhibit FCV in guinea pigs. Two experimental types of glomerulonephritis, nephrotoxic serum (NTS) nephritis in rats and immune complex nephritis in (NZW X NZB) F1 mice, in which Type II and III reactions might participate in the onset and the development of the disease, were slightly inhibited by SCC in terms of the biochemical changes of blood and urine parameters and histopathological scores. A moderate remission of the onset and development of these two experimental types of nephritis was recognized by the administration of prednisolone. Delayed hypersensitivity reaction as a Type IV reaction caused by sheep red blood cells (SRBC) in sensitized mouse footpad was not affected by SCC. Prednisolone clearly inhibited the SRBC induced footpad reaction in mice. IgM antibody production in mice and IgE antibody production in rats were not influenced by daily injection of SCC.

Animals↗
PubMed2004

DNA adducts with chlorophyll and chlorophyllin as antimutagenic agents: synthesis, stability, and structural features.

Porphyrins and their metal derivatives are strong DNA binders with association constants of 10(5) M(-1) to 10(7) M(-1). Some of these compounds have been used for radiation sensitization therapy of cancer and are targeted to interact with cellular DNA. Chlorophyll (CHL) and chlorophyllin (CHLN), a food-grade derivative of chlorophyll, the ubiquitous green plant pigment widely consumed by humans, are potent inhibitors of experimental carcinogenesis. The aim of this report was to examine the interaction of calf-thymus DNA with CHL and CHLN in aqueous solution at physiological pH, with pigment/DNA(phosphate) molar ratios (r) of 1/80 to 1/2. Fourier transform infrared (FTIR) difference spectroscopic method was used to determine the pigment binding mode, binding constant, sequence selectivity, DNA secondary structure and structural variations of the pigment-DNA complexes in aqueous solution.

Animals↗
PubMed2000

Green fluorescent protein photobleaching: a model for protein damage by endogenous and exogenous singlet oxygen.

Characterization of protein damage during photosensitization of chlorin e6-treated cells was performed using the green fluorescent protein (GFP). The GFP-chromophore damage caused by singlet oxygen was studied in COS 7 kidney cells and E. coli bacteria following light irradiation. Electron spin resonance (ESR) revealed the generation of endogenous singlet oxygen (1O2) by photoactivated GFP, an effect similar to that produced by the exogenous photosensitizer chlorin e6. A light dose-dependent photobleaching effect of GFP was pronounced at low pH or upon photosensitization with chlorin e6. However, the 1O2 quenchers beta-carotene and sodium azide minimized GFP photo-bleaching. Gel electrophoresis of photosensitized GFP followed by fluorescence multi-pixel spectral imaging revealed the binding of chlorin e6 to GFP, affecting the photobleaching efficacy. Fluorescence multi-pixel spectral imaging of GFP-transfected COS 7 cells demonstrated the presence of GFP in the cytoplasm and nucleus, while chlorin e6 was found to be concentrated in the perinuclear vesicles. Exposure of the cells to light induced GFP photobleaching in the close vicinity of chlorin e6 vesicles. We conclude that photoactivated GFP generates endogenous 1O2, inducing chromophore damage, which can be enhanced by the cooperation of exogenous chlorin e6.

Animals↗
PubMed2000

Scavenger-receptor targeted photodynamic therapy.

Covalent conjugation of a photosensitizer to a ligand that specifically recognized and internalized by a cell-surface receptor may be a way of improving the selectivity of photodynamic therapy (PDT). The class A Type-I scavenger receptor of macrophages, which among other ligands recognizes maleylated serum albumin and has a high capacity is a good candidate for testing this approach. Chlorin(e6) was covalently attached to bovine serum albumin to give conjugates with molar substitution ratios of 1:1 and 3:1 (dye to protein), and these conjugates could then be further modified by maleylation. A novel way of purifying the conjugates by acetone precipitation was developed in order to remove traces of unbound dye that could not be accomplished by size-exclusion chromatography. Conjugates were characterized by polyacrylamide gel electrophoresis and thin-layer chromatography. Photosensitizer uptake was measured by target J774 murine macrophage-like cells and nontarget OVCAR-5 human ovarian cancer cells, and phototoxicity was examined after illumination by a 660 nm diode laser by a tetrazolium assay. All of the purified conjugates were taken up by and after illumination killed J774 cells while there was only small uptake and no phototoxicity toward OVCAR-5 cells. The higher dye:protein ratio and maleylation of the conjugates both produced higher uptakes and lower survival ratios in J774 cells. The uptake and phototoxicity by J774 cells were decreased after incubation at 4 degrees C demonstrating internalization, and confocal microscopy with organelle-specific green fluorescent probes showed largely lysosomal localization. Uptake and phototoxicity by J774 cells could both be competed by addition of the scavenger receptor ligand maleylated albumin. These data show that scavenger receptor-targeted PDT gives a high degree of specificity toward macrophages and may have applications in the treatment of tumors and atherosclerosis.

Animals↗
PubMed2002

Rapid control of wound infections by targeted photodynamic therapy monitored by in vivo bioluminescence imaging.

The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. In this study we report on the first use of a photochemical approach to destroy bacteria infecting a wound in an animal model. Following topical application, a targeted polycationic photosensitizer conjugate between poly-L-lysine and chlorin(e6) penetrated the gram (-) outer bacterial membrane, and subsequent activation with 660 nm laser light rapidly killed Escherichia coli infecting excisional wounds in mice. To facilitate real-time monitoring of infection, we used bacteria that expressed the lux operon from Photorhabdus luminescens; these cells emitted a bioluminescent signal that allowed the infection to be rapidly quantified, using a low-light imaging system. There was a light-dose dependent loss of luminescence in the wound treated with conjugate and light, not seen in untreated wounds. Treated wounds healed as well as control wounds, showing that the photodynamic treatment did not damage the host tissue. Our study points to the possible use of this methodology in the rapid control of wounds and other localized infections.

Animals↗
PubMed2002

Internalization of aggregated photosensitizers by tumor cells: subcellular time-resolved fluorescence spectroscopy on derivatives of pyropheophorbide-a ethers and chlorin e6 under femtosecond one- and two-photon excitations.

Amphiphilic sensitizers self-associate in aqueous environments and form aggregated species that exhibit no or only negligible photodynamic activity. However, amphiphilic photosensitizers number among the most potent agents of photodynamic therapy. The processes by which these sensitizers are internalized into tumor cells have yet to be fully elucidated and thus remain the subject of debate. In this study the uptake of photosensitizer aggregates into tumor cells was examined directly using subcellular time-resolved fluorescence spectroscopy with a high temporal resolution (20-30 ps) and high sensitivity (time-correlated single-photon counting). The investigations were performed on selected sensitizers that exhibit short fluorescence decay times (< 50 ps) in aggregated form. Derivatives of pyropheophorbide-a ether and chlorin e6 with varying lipophilicity were used for the study. The characteristic fluorescence decay times and spectroscopic features of the sensitizer aggregates measured in aqueous solution also could be observed in A431 human endothelial carcinoma cells administered with these photosensitizers. This shows that tumor cells can internalize sensitizers in aggregated form. Uptake of aggregates and their monomerization inside cells were demonstrated directly for the first time by means of fluorescence lifetime imaging with a high temporal resolution. Internalization of the aggregates seems to be endocytosis mediated. The degree of their monomerization in tumor cells is strongly influenced by the lipophilicity of the compounds.

Chlorophyll↗
PubMedDate not supplied

Preclinical evaluation of a novel water-soluble chlorin E6 derivative (BLC 1010) as photosensitizer for the closure of the neovessels.

In the present study, photodynamic activity of a novel photosensitizer (PS), Chlorin e(6)-2.5 N-methyl-d-glucamine (BLC 1010), was evaluated using the chorioallantoic membrane (CAM) as an in vivo model. After intravenous (i.v.) injection of BLC 1010 into the CAM vasculature, the applicability of this drug for photodynamic therapy (PDT) was assessed in terms of fluorescence pharmacokinetics, i.e. leakage from the CAM vessels, and photothrombic activity. The influence of different PDT parameters including drug and light doses on the photodynamic activity of BLC 1010 has been investigated. It was found that, irrespective of drug dose, an identical continuous decrease in fluorescence contrast between the drug inside and outside the blood vessels was observed. The optimal treatment conditions leading to desired vascular damage were obtained by varying drug and light doses. Indeed, observable damage was achieved when irradiation was performed at light doses up to 5 J/cm(2) 1 min after i.v. injection of drug doses up to 0.5 mg/kg body weight(b.w.). However, when irradiation with light doses of more than 10 J/cm(2) was performed 1 min after injection of drug doses up to 2 mg/kg body weight, this led to occlusion of large blood vessels. It has been demonstrated that it is possible to obtain the desired vascular occlusion and stasis with BLC 1010 for different combinations of drug and/or light doses.

Animals↗