Protoporphyrin IX

About: Protoporphyrin IX is a research topic. Over the lifetime, 2250 publications have been published within this topic receiving 65544 citations. The topic is also known as: PpIX.

Endogenous porphyrin distribution induced by 5-aminolaevulinic acid in the tissue layers of the gastrointestinal tract.

Abstract: The accumulation of endogenous porphyrins in rats following systemic administration of 5-aminolaevulinic acid (ALA) has been examined to assess the photosensitization characteristics of this technique for photodynamic therapy (PDT) and chemical extraction assays with fluorescence and absorbance detection of the porphyrin content have been carried out. We compared the results obtained using quantitative microfluorimetry on normal gastric and colonic tissues in rats at 0.5, 1, 2, 4 and 6 h and chemically induced duodenal tumours 2 and 4.5 h after intravenous administration of ALA at a dose of 200 mg kg-1. With chemical extraction followed by high performance liquid chromatography analysis, protoporphyrin IX (PpIX) was found to be the predominant porphyrin present, reaching peak levels of several microgrammes per gramme at 2-4 h in each type of tissue; a small amount of coproporphyrin was detected at 0.5 and 2 h in normal gastric mucosa and duodenal tumour respectively. Both the extraction assay and quantitative microfluorimetry showed that the porphyrin fluorescence builds up rapidly in the mucosal layers of the colon and stomach, reaching a maximum at 2 h, whereas lower fluorescence levels were found with a slower rate of accumulation in the corresponding muscularis layers. A significant PpIX content was found in the duodenal tumour, with a maximum of 7.1 micrograms g-1 4.5 h after ALA administration. We conclude that systemic administration of ALA can induce effective tissue sensitization with protoporphyrin IX and appears to be a promising technique for PDT.

Protoporphyrin IX Nanoparticle Carrier: Preparation, Optical Properties, and Singlet Oxygen Generation

Abstract: The present study is focused on developing a nanoparticle carrier for the photosensitizer protoporphyrin IX for use in photodynamic therapy. The entrapment of protoporphyrin IX (Pp IX) in silica spheres was achieved by modification of Pp IX molecules with an organosilane reagent. The immobilized drug preserved its optical properties and the capacity to generate singlet oxygen, which was detected by a direct method from its characteristic phosphorescence decay curve at near-infrared and by a chemical method using 1,3-diphenylisobenzofuran to trap singlet oxygen. The lifetime of singlet oxygen when a suspension of Pp IX-loaded particles in acetonitrile was excited at 532 nm was determined as 52 micros, which is in good agreement with the value determined for methylene blue in acetonitrile solution under the same conditions. The Pp IX-loaded silica particles have an efficiency of singlet oxygen generation (eta Delta) higher than the quantum yield of free porphyrins. This high efficiency of singlet oxygen generation was attributed to changes on the monomer-dimer equilibrium after photosentisizer immobilization.

Light-Induced Lysis and Carotenogenesis in Myxococcus xanthus

Abstract: Burchard, Robert P. (University of Minnesota, Minneapolis), and Martin Dworkin. Light-induced lysis and carotenogenesis in Myxococcus xanthus. J. Bacteriol. 91:535-545. 1966.-Myxococcus xanthus, grown vegetatively in the light, developed an orange carotenoid after the cells entered stationary phase of growth; pigment content increased with age. Cells grown in the dark did not develop carotenoid and could be photolysed by relatively low-intensity light only during stationary phase; rate of photolysis increased with age. Photolysis adhered to the reciprocity law, was temperature-independent and oxygen-dependent, and required the presence of nonspecific, monovalent cations; it was inhibited by one of several divalent cations. Logarithmic-phase cells were photosensitized by 100,000 x g pellet preparations of sonic-treated stationary-phase cells grown in the light and dark. A porphyrin with a Soret band at 408 mmu was isolated from photosensitive cells; logarithmic-phase cells contained about 1/16 the amount of porphyrin of stationary-phase cells. The purified material had spectral and chemical properties of protoporphyrin IX and photosensitized logarithmic-phase cells. Its spectrum was similar to the action spectrum for photolysis. We concluded that protoporphyrin IX is the natural endogenous photosensitizer. Carotenogenesis was stimulated by light in the blue-violet region of the visible spectrum and was inhibited by diphenylamine, resulting in photosensitivity of the cells. Photoprotection by carotenoid was lost in the cold. A mutant which synthesized carotenoid in the light and dark was photosensitive only after growth in diphenylamine. The ecological significance of these phenomena is discussed.

Protoporphyrin IX: the Good, the Bad, and the Ugly.

Abstract: Protoporphyrin IX (PPIX) is ubiquitously present in all living cells in small amounts as a precursor of heme. PPIX has some biologic functions of its own, and PPIX-based strategies have been used for cancer diagnosis and treatment (the good). PPIX serves as the substrate for ferrochelatase, the final enzyme in heme biosynthesis, and its homeostasis is tightly regulated during heme synthesis. Accumulation of PPIX in human porphyrias can cause skin photosensitivity, biliary stones, hepatobiliary damage, and even liver failure (the bad and the ugly). In this work, we review the mechanisms that are associated with the broad aspects of PPIX. Because PPIX is a hydrophobic molecule, its disposition is by hepatic rather than renal excretion. Large amounts of PPIX are toxic to the liver and can cause cholestatic liver injury. Application of PPIX in cancer diagnosis and treatment is based on its photodynamic effects.

Effectiveness of delta-aminolevulinic acid-induced protoporphyrin as a photosensitizer for photodynamic therapy in vivo.

Abstract: We examined the effectiveness of systemic administration of delta-aminolevulinic acid (delta-ALA) to induce endogenous protoporphyrin as a regimen for use in photodynamic therapy (PDT) of transplanted R3230AC rat mammary adenocarcinomas in vivo. Levels of porphyrins synthesized in various tissues after systemic administration of delta-ALA differed, with their accumulation in tumor tissue being dependent on both the dose and the time after delta-ALA administration. Tumor, liver, and intestine contained greater than 3.0 micrograms porphyrin/g tissue at 3 h after delta-ALA injection, whereas porphyrin levels in rat skin and muscle at that time were an order of magnitude lower. Analysis of tissue by HPLC revealed that the predominant porphyrin synthesized in tumors was protoporphyrin IX, whereas in liver, 18% of the total porphyrin detected was protoporphyrin IX, and in muscle, it was undetectable. Time-dependent studies of the uptake of 14C label from delta-ALA into the various tissues were not predictive of either the total amount of porphyrin or which porphyrin species would be present at 3 h after delta-ALA injection. Additionally, no simple relationship was apparent between the activities of certain selected enzymes involved in heme biosynthesis and the concentrations of porphyrins in the different tissues. High levels of tumor protoporphyrin IX were sustained by administration of two sequential doses of delta-ALA, at 3.0 and 1.5 h prior to irradiation. Using these treatment conditions, we inhibited R3230AC growth to an extent that was comparable to that obtained for Photofrin-induced PDT. High energy phosphate metabolism, measured by nuclear magnetic resonance spectroscopy in vivo, was dramatically impaired after delta-ALA-based PDT, with tumor ATP levels reduced to near zero by 4 h after irradiation. Our results demonstrated that delta-ALA-based PDT may be an alternative to current treatment protocols that use exogenously administered photosensitizers.