Phototoxicity of protoporphyrin as related to its subcellular localization in mice livers after short-term feeding with griseofulvin

Abstract

In mice, feeding with griseofulvin leads to the rapid accumulation of protoporphyrin in liver mitochondria. When liver mitochondria from mice fed with griseofulvin for 2 days are exposed to irradiation (320-400 nm), uncoupling of oxidative phosphorylation followed by inhibition of respiration occurs at light doses above 3-5 kJ/m2. When combined preparations of mitochondria and lysosomes are irradiated, inactivation of enzymes occurs in the following order: succinate dehydrogenase greater than glutamate dehydrogenase greater than acid phosphatase greater than beta-glucuronidase. Qualitatively, the photodamaging effect of endogenously produced protoporphyrin is indistinguishable from that of externally added protoporphyrin. Quantitatively, however, when protoporphyrin is added externally, more protoporphyrin is taken up by lysosomes, and photoinactivation of the lysosomal enzymes is correspondingly more severe. The results are further evidence that porphyrin-induced photodamage is largely determined by the solubility properties of the porphyrins and the target structures [Sandberg & Romslo (1980) Biochim. Biophys. Acta 593, 187-195], and also that protoporphyrin-induced photodamage is essentially similar whether protoporphyrin is generated endogenously or added exogenously.

Protoporphyrin IX–β‐Cyclodextrin Bimodal Conjugate: Nanosized Drug Transporter and Potent Phototoxin

“…2) revealed a significant mitochondrial accumulation for both the parent and daughter species and in general there was no notable change of that trend following PpIX conjugation with bCD. Although mitochondrial localization was evident for both compounds in accordance with previous reports on PpIX (31), we could not verify a notable lysosomal component expected upon exogenous PpIX administration (31) for either PpIX or PpIX + bCD and in either of the cell lines studied (Fig. 3).…”

Subcellular Localization of Photofrin and Aminolevulinic Acid and Photodynamic Cross‐Resistance in Vitro in Radiation‐Induced Fibrosarcoma Cells Sensitive or Resistant to Photofrin‐Mediated Photodynamic Therapy

“…We observed no differences between RIF-1 and RE-8A cells in terms of mitochondrial localization of ALA-induced PpIX, based on the colocalization with Rh-123. This is understandable because PpIX produced in the mitochondria should not, a priori, have comparable subcellular localization as exogenous porphyrin that must be transported to specific sites, such as mitochondria, in the process of which binding factors play a major role (40,41). The FUF-8A cells were also found not to be cross-resistant to ALA-PDT at 1 or 5 h incubation, which is consistent with the identical PpIX localization.…”

AN ACTION SPECTRUM FOR BLUE AND NEAR ULTRAVIOLET IN ACTIVATION OF Propionibacterium acnes; WITH EMPHASIS ON A POSSIBLE PORPHYRIN PHOTOSENSITIZATION

“…Porphy-ins were extracted from the bacteria by ethylacetate/acetic acid (3: 1. volivol). transferred to a 3 M HCI solution and detcrmincd fluorimetrically as described by Sandberg and Romslo (1981). Protoporphyrin IX (Porphyrin Products, Utah, USA), dissolved in 0.01 M NaOH and 20% CzHsOH and stored at -20°C in the dark, was used as a standard.…”