caa a22 4500 46325418X CHVBK 20180405153349.0 cr unu---uuuuu 170326e20070901xx s 000 0 eng 10.1007/s10571-007-9154-0 doi (NATIONALLICENCE)springer-10.1007/s10571-007-9154-0 Metabolization of Porphyrinogenic Agents in Brain: Involvement of the Phase I Drug Metabolizing System. A Comparative Study in Liver and Kidney [Elektronische Daten] [Jimena Lavandera, Alcira Batlle, Ana Buzaleh] (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 24h. 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. Springer Science+Business Media, LLC, 2007 Drug metabolizing system nationallicence Cytochrome P-450 nationallicence NADPH Cytochrome P-450 reductase nationallicence Porphyrinogenic drugs nationallicence δ-Aminolevulinic acid nationallicence Lavandera Jimena Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas José de San Martín, University of Buenos Aires, Viamonte 188l 10°, "A”, C1056ABA, Buenos Aires, Argentina aut Batlle Alcira Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas José de San Martín, University of Buenos Aires, Viamonte 188l 10°, "A”, C1056ABA, Buenos Aires, Argentina aut Buzaleh Ana Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas José de San Martín, University of Buenos Aires, Viamonte 188l 10°, "A”, C1056ABA, Buenos Aires, Argentina aut Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/6(2007-09-01), 717-729 0272-4340 27:6<717 2007 27 10571 https://doi.org/10.1007/s10571-007-9154-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10571-007-9154-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lavandera Jimena Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas José de San Martín, University of Buenos Aires, Viamonte 188l 10°, "A”, C1056ABA, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Batlle Alcira Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas José de San Martín, University of Buenos Aires, Viamonte 188l 10°, "A”, C1056ABA, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Buzaleh Ana Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas José de San Martín, University of Buenos Aires, Viamonte 188l 10°, "A”, C1056ABA, Buenos Aires, Argentina aut NATIONALLICENCE 773 0- Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/6(2007-09-01), 717-729 0272-4340 27:6<717 2007 27 10571 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer