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.

Characteristics of 5-aminolaevulinic acid-induced protoporphyrin IX fluorescence in human skin in vivo.

Abstract: Background/Purpose: Topical photodynamic therapy (PDT) is increasingly being used to treat skin cancers. Knowledge of the detailed characteristics of 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence in diseased and normal skin is incomplete. Understanding the characteristics of PpIX fluorescence in normal skin may facilitate optimization of PDT regimes while minimizing side effects in the surrounding normal skin. We investigated the characteristics of ALA-induced PpIX fluorescence in normal skin. Methods: ALA was applied to the arm, back and leg skin of 21 healthy volunteers for 1–6 h, and PpIX fluorescence was measured for up to 24 h after ALA application using a fluorescent spectrometer. The effect of tape stripping on fluorescence was also examined. Results: Considerable inter-subject variation was observed in the time to reach peak PpIX fluorescence. Intra-subject variation in the time to peak fluorescence was dependent on ALA application time. Six hours after ALA application, no significant difference was observed in the degree of fluorescence achieved irrespective of ALA application times ranging between 1 and 6 h. PpIX fluorescence was reduced on the leg and increased by tape stripping. Conclusions: Marked inter- and intra-subject variation in ALA-induced PpIX fluorescence occurs in normal human skin. ALA application time, body site and the state of the stratum corneum are all determinants of PpIX fluorescence within subjects and these factors need to be taken into account in optimization of PDT regimes.

Porphyrin sensitization and intracellular calcium changes in the prokaryote Propionibacterium acnes

Abstract: Photosensitization induces intracellular free calcium changes ([Ca 2+ ] i ) in some eukaryotic cell systems which either contribute to or protect against cell inactivation. We have investigated whether or not similar changes can be induced in prokaryotes. The skin bacterium Propionibacterium acnes was sensitized using protoporphyrin IX (PP IX) or 5-aminolevulinic acid (ALA). Exogenous ALA resulted in either a preferential accumulation of protoporphyrin (ALA-PP) or of coproporphyrin and/or uroporphyrin (ALA-CP/UP) in P. acnes . For PP IX or ALA-PP sensitization, exposure to broad-band red light resulted in an increase in [Ca 2+ ] i . For ALA-PP sensitization, this increase was transient and [Ca 2+ ] i returned to basal levels within 5–10 min after irradiation. However, the elevated [Ca 2+ ] i levels obtained after PP IX sensitization were maintained for at least 1 h after irradiation. In both cases, the reduction in the external calcium concentration led to an enhancement in the cell survival, indicating that induced [Ca 2+ ] i changes may participate in photoinactivation. Sensitization by hydrophilic coproporphyrin and/or uroporphyrin (ALA-CP/UP) did not affect the [Ca 2+ ] i , levels but higher levels of cell inactivation were obtained. It therefore appears that damage to membrane-associated components is at least partly responsible for [Ca 2+ ] i alterations after photosensitization.

Protoporphyrin IX fluorescence kinetics and localization after topical application of ALA pentyl ester and ALA on hairless mouse skin with UVB-induced early skin cancer.

Abstract: In order to improve the efficacy of 5-aminolevulinic acid-based (ALA) photodynamic therapy (PDT), different ALA derivatives are presently being investigated. ALA esters are more lipophilic and therefore may have better skin penetration properties than ALA, possibly resulting in enhanced protoporphyrin IX (PpIX) production. In previous studies it was shown that ALA pentyl ester (ALAPE) does considerably enhance the PpIX production in cells in vitro compared with ALA. We investigated the in vivo PpIX fluorescence kinetics after application of ALA and ALAPE to hairless mice with and without UVB-induced early skin cancer. ALA and ALAPE (20% wt/wt) were applied topically to the mouse skin and after 30 min, the solvent was wiped off and PpIX fluorescence was followed in time with in vivo fluorescence spectroscopy and imaging. At 6 and 12 h after the 30 min application, skin samples of visible lesions and adjacent altered skin (UVB-exposed mouse skin) and normal mouse skin were collected for fluorescence microscopy. From each sample, frozen sections were made and phase contrast images and fluorescence images were recorded. The in vivo fluorescence kinetics showed that ALAPE induced more PpIX in visible lesions and altered skin of the UVB-exposed mouse skin, but not in the normal mouse skin. In the microscopic fluorescence images, higher ALAPE-induced PpIX levels were measured in the stratum corneum, but not in the dysplastic layer of the epidermis. In deeper layers of the skin, PpIX levels were the same after ALA and ALAPE application. In conclusion, ALAPE does induce higher PpIX fluorescence levels in vivo in our early skin cancer model, but these higher PpIX levels are not located in the dysplastic layer of the epidermis.

On the selectivity of 5-aminolevulinic acid-induced protoporphyrin IX formation

Abstract: Due to its capability to induce accumulation of protoporphyrin IX (PpIX) selectively in a multitude of different pathologies, 5-aminolevulinic acid (ALA) and its derivatives have attracted enormous attention in the field of photodynamic therapy (PDT) in the past two decades. The photochemical and photophysical properties of PpIX have been used for the fluorescence photodetection and photodynamic treatment of neoplasms in several medical indications in which conversion of ALA into PpIX seems to take place preferentially. Recently, this has led to the approval of this therapy for the treatment of actinic keratosis and basal cell carcinoma. When applied topically or systemically, ALA bypasses the negative feedback control that haem exerts on the enzyme ALA synthase (ALAS), which catalyses the natural production of this delta-amino acid, thereby temporarily boosting the generation of PpIX, the direct precursor of haem. Despite considerable interest in this treatment methodology, only little is known concerning the reasons for the selective accumulation of PpIX in neoplastic tissue upon ALA administration. Following an introduction into the biochemical as well as the chemical principles of haem synthesis, the present review tries to summarise experimental evidences of the mechanisms underlying preferential production of PpIX in neoplastic tissues. Thereby, morphological, environmental, enzymatic, as well as cell-specific factors will be discussed.

N-Methyl Mesoporphyrin IX Inhibits Phycocyanin, but Not Chlorophyll Synthesis in Cyanidium caldarium

Abstract: The ability of N -methyl mesoporphyrin IX (NMMP) to block heme synthesis by specifically inhibiting enzymic iron insertion into protoporphyrin IX was exploited to test whether heme is a precursor of the bilin chromophore of phycocyanin (PC). A strain of the unicellular rhodophyte Cyanidium caldarium which forms normal amounts of both chlorophyll (Chl) and PC in the dark was employed to avoid phototoxic effects of exogenous porphyrins. Relative Chl and PC content were assayed spectrophotometrically on whole cell suspensions. When cells were grown in the dark on a glucose-based heterotrophic medium at 42°C, neither division rate nor Chl synthesis was affected by NMMP up to 3.0 micromolar and for as long as 72 hours. NMMP had a dose-dependent inhibitory effect on PC synthesis. PC to Chl absorbance ratios, relative to control cell values, were 100%, 89%, 86%, and 50% in cells grown for 48 hours with 0.3, 1.0, 3.0, and 10.0 micromolar NMMP, respectively. NMMP also caused the accumulation of intracellular protoporphyrin. The ability of NMMP to cause intracellular accumulation of protoporphyrin and to block PC synthesis specifically while allowing normal Chl formation is consistent with its action as a specific inhibitor of enzymic iron chelation, and supports the role of heme as a precursor to the phycobilins.