Lysosome destruction and lipoperoxide formation due to active oxygen generated from haematoporphyrin and UV irradiation

Torinuki, Wakio; Miura, Takashi; Seiji, Makoto

doi:10.1111/j.1365-2133.1980.tb05667.x

Cited by 72 publications

(23 citation statements)

References 13 publications

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“…The hydrophobic components of HPD include DHE, which is known to localize within the membranous structures including those of the plasma membrane and subcellular organelles like mitochondria, the endoplasmic reticulum, and lysosomes (20,(33)(34)(35)(36)(37). Membranes, therefore, appear to be the principal targets for the phototoxic action of porphyrins.…”

Section: Discussionmentioning

confidence: 99%

A novel mechanism for the generation of superoxide anions in hematoporphyrin derivative-mediated cutaneous photosensitization. Activation of the xanthine oxidase pathway.

Athar¹,

Elmets²,

Bickers³

et al. 1989

J. Clin. Invest.

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Prior studies, both in vitro and in vivo, have suggested that cutaneous porphyrin photosensitization requires the generation of superoxide anion 2O-) and various other reactive oxygen metabolites. No unifying concept has emerged, however, that unequivocally demonstrates the source of generation of these species. Since xanthine oxidase is known to generate *02 in reperfused ischemic tissue and in certain inflammatory disorders, we attempted to assess its role in porphyrin photosensitization. C3H mice were rendered photosensitive by the intraperitoneal administration of dihematoporphyrin ether (DHE) (5 mg/kg) followed by irradiation with visible light. Murine ear swelling was used as a marker of the acute photosensitization response and involvement of oxygen radicals was evaluated using electron spin resonance (ESR) spectroscopy. The administration of allopurinol, a potent inhibitor of xanthine oxidase, afforded 90% protection against DHE-mediated acute photosensitivity in vivo. Furthermore, xanthine oxidase activity was twofold higher in the skin of photosensitized mice than in unirradiated animals. ESR spectra of 5,5-dimethyl-1-pyrroline N-oxide-trapped radicals from the skin of photosensitized mice verified the presence of O2 and 'OH, while neither of these species was detected in the skin of control mice or mice receiving allopurinol. The administration of a soybean trypsin inhibitor or verapamil before irradiation also partially blocked the photosensitivity response, suggesting that calcium-dependent proteases play a role in the activation of xanthine oxidase in this photodynamic process. These data provide in vivo evidence for the involvement of O0 in DHE-mediated cutaneous photosensitization and suggest that these radicals are generated through the activation of the xanthine oxidase pathway. The administration of allopurinol and calcium channel blockers may thus offer new approaches for the treatment of cutaneous porphyrin photosensitization.

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Section: Discussionmentioning

confidence: 99%

A novel mechanism for the generation of superoxide anions in hematoporphyrin derivative-mediated cutaneous photosensitization. Activation of the xanthine oxidase pathway.

Athar¹,

Elmets²,

Bickers³

et al. 1989

J. Clin. Invest.

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“…The finding that BHT protected against phototoxicity indicated that the generation of free radicals could play a part in causing phototoxicity. It is known that many compounds such as bleomyein (Antholine et al 1985) and porphyrin derivatives (Torinuki et al 1980) generate reactive oxygen in bringing about phototoxicity. Thus, one reason for the protective effect of BHT is probably related to the scavenging effect of free radicals directly generated in photochemical reactions; however, it is well known that reactive oxygen species are also generated in many steps of inflammatory reactions.…”

Section: Introductionmentioning

confidence: 99%

Important role of oxygen metabolites in quinolone antibacterial agent-induced cutaneous phototoxicity in mice

Wagai

Tawara

1991

Arch Toxicol

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We investigated whether or not the generation of reactive oxygens and toxic photoproducts participated in the cutaneous phototoxicity mechanisms induced by the quinolone derivatives, ofloxacin (OFLX), enoxacin, lomefloxacin, ciprofloxacin and DR-3355 (the s-isomer of OFLX) in a mouse model. Pretreatment of Balb/c mice with allopurinol, soybean trypsin inhibitor, catalase and beta-carotene gave significant protection against ear swelling reactions induced by oral administration of quinolones and following ultraviolet-A (UVA) irradiation. Pretreatment with diethyldithiocarbamate augmented the swelling. No swelling was observed with direct injection into the auricle of UVA-pretreated photoproducts of the quinolones. These results showed that cutaneous phototoxicity did not depend on the generation of toxic photoproducts and suggested that oxygen metabolites generated in the xanthine oxidase pathway participated in the toxicity.

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“…Direct killing, in vitro, can result from singlet oxygen damage to biomembranes (Bertolini et al, 1984;Grossweiner, 1984). In particular, damage to lysosomes (Torinuki et al, 1980;Volden et al, 1981;Santus et al, 1983;Reyftmann et al, 1986) results in cell autolysis and damage to mitochondria (Sandberg et al, 1982;Burns et al, 1982;Singh et al, 1987) results in disruption of oxidative phosphorylation. Indirect killing, in vivo, can result from microvascular damage causing cessation of blood flow and secondary tumour cell death (Henderson et al, 1985;Selman et al, 1984).…”

mentioning

confidence: 99%

Non-invasive monitoring of photodynamic therapy with 99technetium HMPAO scintigraphy

Moore¹,

Chapman²,

Mokrzanowski³

et al. 1992

Br J Cancer

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Summary The effect of photodynamic therapy (PDT) on tumour perfusion in both anaplastic (R3327-AT) and well differentiated (R3327-H) Dunning prostatic tumours was studied using the radiopharmaceutical 99Technetium hexamethylpropyleneamine oxime (99"Tc-HMPAO). Tumours in the left flanks of rats (Copenhage x Fischer, F1 hybrids) were treated with interstitial PDT when their volumes reached 2-3 cm3. Qualitative and quantitative data from pre-and post-PDT scintigraphy revealed a light-dose-dependent shut-down of tumour perfusion which was also time-dependent. Maximal shut-down, following a 1,600J light-dose, occurred about 8 h post-PDT. Light exposure 2 h after the intravenous administration of the photosensitiser (Photofrin II) produced a greater vascular shut-down than did light exposure 24 h after the administration of the drug. Regional differences in perfusion within treated and non-treated tumours were measured by tomographic procedures. Light-dose-dependent volumes of perfusion shut-down were demonstrated in addition to the naturally occurring regional differences in tumour perfusion. This radiopharmaceutical may have future utility for monitoring the clinical treatment of solid tumours with PDT.

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Lysosome destruction and lipoperoxide formation due to active oxygen generated from haematoporphyrin and UV irradiation

Cited by 72 publications

References 13 publications

A novel mechanism for the generation of superoxide anions in hematoporphyrin derivative-mediated cutaneous photosensitization. Activation of the xanthine oxidase pathway.

A novel mechanism for the generation of superoxide anions in hematoporphyrin derivative-mediated cutaneous photosensitization. Activation of the xanthine oxidase pathway.

Important role of oxygen metabolites in quinolone antibacterial agent-induced cutaneous phototoxicity in mice

Non-invasive monitoring of photodynamic therapy with 99technetium HMPAO scintigraphy

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