Enhancement of aminolevulinic acid based photodynamic therapy by adriamycin
This paper reports on studies that evaluate the interaction between δ-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) and adriamycin (ADM) in an animal model system. Two groups of mice bearing a transplantable mammary adenocarcinoma received ADM i.p. in a single dose of 5 mg (low dose) an...
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1997
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Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03043835_v121_n1_p105_Casas http://hdl.handle.net/20.500.12110/paper_03043835_v121_n1_p105_Casas |
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paper:paper_03043835_v121_n1_p105_Casas2023-06-08T15:29:17Z Enhancement of aminolevulinic acid based photodynamic therapy by adriamycin Casas, Adriana Gabriela Fukuda, Haydeé Batlle, Alcira María del Carmen δ-aminolevulinic acid Adriamycin Antitumour drugs Combination therapy Photodynamic therapy aminolevulinic acid dna doxorubicin free radical hydroxyl radical malonaldehyde peroxide porphobilinogen synthase porphyrin reactive oxygen metabolite semiquinone animal experiment animal model animal tissue article breast adenocarcinoma cancer inhibition cancer transplantation controlled study cytotoxicity dna damage drug mechanism drug toxicity enzyme activity heart intraperitoneal drug administration laser lipid peroxidation liver male mouse nonhuman photodynamic therapy priority journal Adenocarcinoma Aminolevulinic Acid Ammonia-Lyases Animals Doxorubicin Drug Therapy, Combination Lipid Peroxidation Liver Male Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Myocardium Neoplasm Transplantation Photochemotherapy Porphobilinogen Synthase Porphyrins Animalia This paper reports on studies that evaluate the interaction between δ-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) and adriamycin (ADM) in an animal model system. Two groups of mice bearing a transplantable mammary adenocarcinoma received ADM i.p. in a single dose of 5 mg (low dose) and 30 mg (high dose) per kg body weight. Sixteen or 40 h after administration of the drug, mice were sacrificed, tumours, livers and hearts were removed and porphyrins, enzyme activities and malondialdehyde content were determined. Tumour explants of ADM-treated mice were incubated with ALA and irradiated with an He-Ne laser. Re-implantation of these in vitro PDT-treated explants into test animals showed that inhibition of tumour growth was significantly enhanced by combined treatment when the low dose of ADM was used. There were no significant changes in porphyrin content, ALA dehydratase and porphobilinogenase activities in the tissues analyzed after ADM treatment as compared with control values. ADM toxicity is thought to be related to semiquinone free radical formation with subsequent generation of reactive oxygen species such as peroxide and hydroxyl radical. These species are considered to initiate lipid peroxidation (LPO) and cause DNA damage. In the case of low-dose treatment with ADM a significant increase in the LPO product, malondialdehyde, was observed after PDT whereas with the high-dose regimen no changes were observed. In the case of explants of (non-irradiated) cardiac tissue malondialdehyde production was also found to be dependent on the dose and time of administration of adriamycin. In our in vivo/in vitro model system we have shown that pre-treatment with ADM increased the cytotoxicity of ALA-PDT at a dosage level of ADM which did not raise LPO levels in heart tissue. The mechanism of this effect has not been clearly elucidated but our data suggest that the observed enhancement of PDT may be attributed in part to the weakening of cellular defence mechanisms by the pre-treatment involving free radical generation by ADM. Fil:Casas, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fukuda, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Del C. Batlle, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 1997 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03043835_v121_n1_p105_Casas http://hdl.handle.net/20.500.12110/paper_03043835_v121_n1_p105_Casas |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
δ-aminolevulinic acid Adriamycin Antitumour drugs Combination therapy Photodynamic therapy aminolevulinic acid dna doxorubicin free radical hydroxyl radical malonaldehyde peroxide porphobilinogen synthase porphyrin reactive oxygen metabolite semiquinone animal experiment animal model animal tissue article breast adenocarcinoma cancer inhibition cancer transplantation controlled study cytotoxicity dna damage drug mechanism drug toxicity enzyme activity heart intraperitoneal drug administration laser lipid peroxidation liver male mouse nonhuman photodynamic therapy priority journal Adenocarcinoma Aminolevulinic Acid Ammonia-Lyases Animals Doxorubicin Drug Therapy, Combination Lipid Peroxidation Liver Male Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Myocardium Neoplasm Transplantation Photochemotherapy Porphobilinogen Synthase Porphyrins Animalia |
spellingShingle |
δ-aminolevulinic acid Adriamycin Antitumour drugs Combination therapy Photodynamic therapy aminolevulinic acid dna doxorubicin free radical hydroxyl radical malonaldehyde peroxide porphobilinogen synthase porphyrin reactive oxygen metabolite semiquinone animal experiment animal model animal tissue article breast adenocarcinoma cancer inhibition cancer transplantation controlled study cytotoxicity dna damage drug mechanism drug toxicity enzyme activity heart intraperitoneal drug administration laser lipid peroxidation liver male mouse nonhuman photodynamic therapy priority journal Adenocarcinoma Aminolevulinic Acid Ammonia-Lyases Animals Doxorubicin Drug Therapy, Combination Lipid Peroxidation Liver Male Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Myocardium Neoplasm Transplantation Photochemotherapy Porphobilinogen Synthase Porphyrins Animalia Casas, Adriana Gabriela Fukuda, Haydeé Batlle, Alcira María del Carmen Enhancement of aminolevulinic acid based photodynamic therapy by adriamycin |
topic_facet |
δ-aminolevulinic acid Adriamycin Antitumour drugs Combination therapy Photodynamic therapy aminolevulinic acid dna doxorubicin free radical hydroxyl radical malonaldehyde peroxide porphobilinogen synthase porphyrin reactive oxygen metabolite semiquinone animal experiment animal model animal tissue article breast adenocarcinoma cancer inhibition cancer transplantation controlled study cytotoxicity dna damage drug mechanism drug toxicity enzyme activity heart intraperitoneal drug administration laser lipid peroxidation liver male mouse nonhuman photodynamic therapy priority journal Adenocarcinoma Aminolevulinic Acid Ammonia-Lyases Animals Doxorubicin Drug Therapy, Combination Lipid Peroxidation Liver Male Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Myocardium Neoplasm Transplantation Photochemotherapy Porphobilinogen Synthase Porphyrins Animalia |
description |
This paper reports on studies that evaluate the interaction between δ-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) and adriamycin (ADM) in an animal model system. Two groups of mice bearing a transplantable mammary adenocarcinoma received ADM i.p. in a single dose of 5 mg (low dose) and 30 mg (high dose) per kg body weight. Sixteen or 40 h after administration of the drug, mice were sacrificed, tumours, livers and hearts were removed and porphyrins, enzyme activities and malondialdehyde content were determined. Tumour explants of ADM-treated mice were incubated with ALA and irradiated with an He-Ne laser. Re-implantation of these in vitro PDT-treated explants into test animals showed that inhibition of tumour growth was significantly enhanced by combined treatment when the low dose of ADM was used. There were no significant changes in porphyrin content, ALA dehydratase and porphobilinogenase activities in the tissues analyzed after ADM treatment as compared with control values. ADM toxicity is thought to be related to semiquinone free radical formation with subsequent generation of reactive oxygen species such as peroxide and hydroxyl radical. These species are considered to initiate lipid peroxidation (LPO) and cause DNA damage. In the case of low-dose treatment with ADM a significant increase in the LPO product, malondialdehyde, was observed after PDT whereas with the high-dose regimen no changes were observed. In the case of explants of (non-irradiated) cardiac tissue malondialdehyde production was also found to be dependent on the dose and time of administration of adriamycin. In our in vivo/in vitro model system we have shown that pre-treatment with ADM increased the cytotoxicity of ALA-PDT at a dosage level of ADM which did not raise LPO levels in heart tissue. The mechanism of this effect has not been clearly elucidated but our data suggest that the observed enhancement of PDT may be attributed in part to the weakening of cellular defence mechanisms by the pre-treatment involving free radical generation by ADM. |
author |
Casas, Adriana Gabriela Fukuda, Haydeé Batlle, Alcira María del Carmen |
author_facet |
Casas, Adriana Gabriela Fukuda, Haydeé Batlle, Alcira María del Carmen |
author_sort |
Casas, Adriana Gabriela |
title |
Enhancement of aminolevulinic acid based photodynamic therapy by adriamycin |
title_short |
Enhancement of aminolevulinic acid based photodynamic therapy by adriamycin |
title_full |
Enhancement of aminolevulinic acid based photodynamic therapy by adriamycin |
title_fullStr |
Enhancement of aminolevulinic acid based photodynamic therapy by adriamycin |
title_full_unstemmed |
Enhancement of aminolevulinic acid based photodynamic therapy by adriamycin |
title_sort |
enhancement of aminolevulinic acid based photodynamic therapy by adriamycin |
publishDate |
1997 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03043835_v121_n1_p105_Casas http://hdl.handle.net/20.500.12110/paper_03043835_v121_n1_p105_Casas |
work_keys_str_mv |
AT casasadrianagabriela enhancementofaminolevulinicacidbasedphotodynamictherapybyadriamycin AT fukudahaydee enhancementofaminolevulinicacidbasedphotodynamictherapybyadriamycin AT batllealciramariadelcarmen enhancementofaminolevulinicacidbasedphotodynamictherapybyadriamycin |
_version_ |
1768543276488458240 |