Metabolization of porphyrinogenic agents in brain: Involvement of the Phase I drug metabolizing system. A comparative study in liver and kidney
(1) We evaluated the involvement of brain mitochondrial and microsomal cytochrome P-450 in the metabolization of known porphyrinogenic agents, with the aim of improving the knowledge on the mechanism leading to porphyric neuropathy. We also compared the response in brain, liver and kidney. To this e...
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| Publicado: |
2007
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02724340_v27_n6_p717_Lavandera http://hdl.handle.net/20.500.12110/paper_02724340_v27_n6_p717_Lavandera |
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paper:paper_02724340_v27_n6_p717_Lavandera |
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dspace |
| 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 Cytochrome P-450 Drug metabolizing system NADPH Cytochrome P-450 reductase Porphyrinogenic drugs alcohol allylisopropylacetamide aminolevulinic acid barbital cytochrome P450 enflurane griseofulvin inhalation anesthetic agent liver enzyme porphyrinogen reduced nicotinamide adenine dinucleotide phosphate ferrihemoprotein reductase xenobiotic agent anesthesia animal experiment article brain brain mitochondrion comparative study controlled study enzyme activity kidney liver male metabolism microsome mouse neuropathy nonhuman porphyria priority journal xenobiotic metabolism Allylisopropylacetamide Aminolevulinic Acid Animals Barbital Brain Cytochrome P-450 Enzyme System Ethanol Griseofulvin Hypnotics and Sedatives Kidney Liver Male Metabolic Detoxication, Phase I Mice Microsomes Mitochondria NADPH-Ferrihemoprotein Reductase Photosensitizing Agents Porphyria, Acute Intermittent Animalia |
| spellingShingle |
δ-Aminolevulinic acid Cytochrome P-450 Drug metabolizing system NADPH Cytochrome P-450 reductase Porphyrinogenic drugs alcohol allylisopropylacetamide aminolevulinic acid barbital cytochrome P450 enflurane griseofulvin inhalation anesthetic agent liver enzyme porphyrinogen reduced nicotinamide adenine dinucleotide phosphate ferrihemoprotein reductase xenobiotic agent anesthesia animal experiment article brain brain mitochondrion comparative study controlled study enzyme activity kidney liver male metabolism microsome mouse neuropathy nonhuman porphyria priority journal xenobiotic metabolism Allylisopropylacetamide Aminolevulinic Acid Animals Barbital Brain Cytochrome P-450 Enzyme System Ethanol Griseofulvin Hypnotics and Sedatives Kidney Liver Male Metabolic Detoxication, Phase I Mice Microsomes Mitochondria NADPH-Ferrihemoprotein Reductase Photosensitizing Agents Porphyria, Acute Intermittent Animalia Lavandera, Jimena Verónica Batlle, Alcira María del Carmen Buzaleh, Ana María Metabolization of porphyrinogenic agents in brain: Involvement of the Phase I drug metabolizing system. A comparative study in liver and kidney |
| topic_facet |
δ-Aminolevulinic acid Cytochrome P-450 Drug metabolizing system NADPH Cytochrome P-450 reductase Porphyrinogenic drugs alcohol allylisopropylacetamide aminolevulinic acid barbital cytochrome P450 enflurane griseofulvin inhalation anesthetic agent liver enzyme porphyrinogen reduced nicotinamide adenine dinucleotide phosphate ferrihemoprotein reductase xenobiotic agent anesthesia animal experiment article brain brain mitochondrion comparative study controlled study enzyme activity kidney liver male metabolism microsome mouse neuropathy nonhuman porphyria priority journal xenobiotic metabolism Allylisopropylacetamide Aminolevulinic Acid Animals Barbital Brain Cytochrome P-450 Enzyme System Ethanol Griseofulvin Hypnotics and Sedatives Kidney Liver Male Metabolic Detoxication, Phase I Mice Microsomes Mitochondria NADPH-Ferrihemoprotein Reductase Photosensitizing Agents Porphyria, Acute Intermittent Animalia |
| description |
(1) We evaluated the involvement of brain mitochondrial and microsomal cytochrome P-450 in the metabolization of known porphyrinogenic agents, with the aim of improving the knowledge on the mechanism leading to porphyric neuropathy. We also compared the response in brain, liver and kidney. To this end, we determined mitochondrial and microsomal cytochrome P-450 levels and the activity of NADPH cytochrome P-450 reductase. (2) Animals were treated with known porphyrinogenic drugs such as volatile anaesthetics, allylisopropylacetamide, veronal, griseofulvin and ethanol or were starved during 24 h. Cytochrome P-450 levels and NADPH cytochrome P-450 reductase activity were measured in mitochondrial and microsomal fractions from the different tissues. (3) Some of the porphyrinogenic agents studied altered mitochondrial cytochrome P-450 brain but not microsomal cytochrome P-450. Oral griseofulvin induced an increase in mitochondrial cytochrome P-450 levels, while chronic Isoflurane produced a reduction on its levels, without alterations on microsomal cytochrome P-450. Allylisopropylacetamide diminished both mitochondrial and microsomal cytochrome P-450 brain levels; a similar pattern was detected in liver. Mitochondria cytochorme P-450 liver levels were only diminished after chronic Isoflurane administration. In kidney only mitochondrial cytochrome P-450 levels were modified by veronal; while in microsomes, only acute anaesthesia with Enflurane diminished cytochrome P-450 content. (4) Taking into account that δ-aminolevulinic acid would be responsible for porphyric neuropathy, we investigated the effect of acute and chronic δ-aminolevulinic acid administration. Acute δ-aminolevulinic acid administration reduced brain and liver cytochrome P-450 levels in both fractions; chronic δ-aminolevulinic acid administration diminished only liver mitochondrial cytochrome P-450. (5) Brain NADPH cytochrome P-450 reductase activity in animals receiving allylisopropylacetamide, dietary griseofulvin and δ-aminolevulinic acid showed a similar profile as that for total cytochrome P-450 levels. The same response was observed for the hepatic enzyme. (6) Results here reported revealed differential tissue responses against the xenobiotics assayed and give evidence on the participation of extrahepatic tissues in porphyrinogenic drug metabolization. These studies have demonstrated the presence of the integral Phase I drug metabolizing system in the brain, thus, total cytochrome P-450 and associated monooxygenases in brain microsomes and mitochondria would be taken into account when considering the xenobiotic metabolizing capability of this organ. © 2007 Springer Science+Business Media, LLC. |
| author |
Lavandera, Jimena Verónica Batlle, Alcira María del Carmen Buzaleh, Ana María |
| author_facet |
Lavandera, Jimena Verónica Batlle, Alcira María del Carmen Buzaleh, Ana María |
| author_sort |
Lavandera, Jimena Verónica |
| title |
Metabolization of porphyrinogenic agents in brain: Involvement of the Phase I drug metabolizing system. A comparative study in liver and kidney |
| title_short |
Metabolization of porphyrinogenic agents in brain: Involvement of the Phase I drug metabolizing system. A comparative study in liver and kidney |
| title_full |
Metabolization of porphyrinogenic agents in brain: Involvement of the Phase I drug metabolizing system. A comparative study in liver and kidney |
| title_fullStr |
Metabolization of porphyrinogenic agents in brain: Involvement of the Phase I drug metabolizing system. A comparative study in liver and kidney |
| title_full_unstemmed |
Metabolization of porphyrinogenic agents in brain: Involvement of the Phase I drug metabolizing system. A comparative study in liver and kidney |
| title_sort |
metabolization of porphyrinogenic agents in brain: involvement of the phase i drug metabolizing system. a comparative study in liver and kidney |
| publishDate |
2007 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02724340_v27_n6_p717_Lavandera http://hdl.handle.net/20.500.12110/paper_02724340_v27_n6_p717_Lavandera |
| work_keys_str_mv |
AT lavanderajimenaveronica metabolizationofporphyrinogenicagentsinbraininvolvementofthephaseidrugmetabolizingsystemacomparativestudyinliverandkidney AT batllealciramariadelcarmen metabolizationofporphyrinogenicagentsinbraininvolvementofthephaseidrugmetabolizingsystemacomparativestudyinliverandkidney AT buzalehanamaria metabolizationofporphyrinogenicagentsinbraininvolvementofthephaseidrugmetabolizingsystemacomparativestudyinliverandkidney |
| _version_ |
1768545463716282368 |
| spelling |
paper:paper_02724340_v27_n6_p717_Lavandera2023-06-08T15:25:06Z Metabolization of porphyrinogenic agents in brain: Involvement of the Phase I drug metabolizing system. A comparative study in liver and kidney Lavandera, Jimena Verónica Batlle, Alcira María del Carmen Buzaleh, Ana María δ-Aminolevulinic acid Cytochrome P-450 Drug metabolizing system NADPH Cytochrome P-450 reductase Porphyrinogenic drugs alcohol allylisopropylacetamide aminolevulinic acid barbital cytochrome P450 enflurane griseofulvin inhalation anesthetic agent liver enzyme porphyrinogen reduced nicotinamide adenine dinucleotide phosphate ferrihemoprotein reductase xenobiotic agent anesthesia animal experiment article brain brain mitochondrion comparative study controlled study enzyme activity kidney liver male metabolism microsome mouse neuropathy nonhuman porphyria priority journal xenobiotic metabolism Allylisopropylacetamide Aminolevulinic Acid Animals Barbital Brain Cytochrome P-450 Enzyme System Ethanol Griseofulvin Hypnotics and Sedatives Kidney Liver Male Metabolic Detoxication, Phase I Mice Microsomes Mitochondria NADPH-Ferrihemoprotein Reductase Photosensitizing Agents Porphyria, Acute Intermittent Animalia (1) We evaluated the involvement of brain mitochondrial and microsomal cytochrome P-450 in the metabolization of known porphyrinogenic agents, with the aim of improving the knowledge on the mechanism leading to porphyric neuropathy. We also compared the response in brain, liver and kidney. To this end, we determined mitochondrial and microsomal cytochrome P-450 levels and the activity of NADPH cytochrome P-450 reductase. (2) Animals were treated with known porphyrinogenic drugs such as volatile anaesthetics, allylisopropylacetamide, veronal, griseofulvin and ethanol or were starved during 24 h. Cytochrome P-450 levels and NADPH cytochrome P-450 reductase activity were measured in mitochondrial and microsomal fractions from the different tissues. (3) Some of the porphyrinogenic agents studied altered mitochondrial cytochrome P-450 brain but not microsomal cytochrome P-450. Oral griseofulvin induced an increase in mitochondrial cytochrome P-450 levels, while chronic Isoflurane produced a reduction on its levels, without alterations on microsomal cytochrome P-450. Allylisopropylacetamide diminished both mitochondrial and microsomal cytochrome P-450 brain levels; a similar pattern was detected in liver. Mitochondria cytochorme P-450 liver levels were only diminished after chronic Isoflurane administration. In kidney only mitochondrial cytochrome P-450 levels were modified by veronal; while in microsomes, only acute anaesthesia with Enflurane diminished cytochrome P-450 content. (4) Taking into account that δ-aminolevulinic acid would be responsible for porphyric neuropathy, we investigated the effect of acute and chronic δ-aminolevulinic acid administration. Acute δ-aminolevulinic acid administration reduced brain and liver cytochrome P-450 levels in both fractions; chronic δ-aminolevulinic acid administration diminished only liver mitochondrial cytochrome P-450. (5) Brain NADPH cytochrome P-450 reductase activity in animals receiving allylisopropylacetamide, dietary griseofulvin and δ-aminolevulinic acid showed a similar profile as that for total cytochrome P-450 levels. The same response was observed for the hepatic enzyme. (6) Results here reported revealed differential tissue responses against the xenobiotics assayed and give evidence on the participation of extrahepatic tissues in porphyrinogenic drug metabolization. These studies have demonstrated the presence of the integral Phase I drug metabolizing system in the brain, thus, total cytochrome P-450 and associated monooxygenases in brain microsomes and mitochondria would be taken into account when considering the xenobiotic metabolizing capability of this organ. © 2007 Springer Science+Business Media, LLC. Fil:Lavandera, J.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A.M.D.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Buzaleh, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2007 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02724340_v27_n6_p717_Lavandera http://hdl.handle.net/20.500.12110/paper_02724340_v27_n6_p717_Lavandera |