Heme oxygenase, aminolevulinate acid synthetase and the antioxidant system in the brain of mice treated with porphyrinogenic drugs.
Several drugs and stress are involved in the triggering of attacks in acute porphyrias. The central nervous system is extremely sensitive to free radical damage because of a relatively low antioxidant capacity. We have demonstrated that mice brain cholinergic system was altered by the effect of some porphyrinogenic agents. The aim of this work was to investigate how known porphyrinogenic drugs affect delta-Aminolevulinic acid synthetase (ALA-S), which is the response of heme oxygenase (HO) to this challenge and to evaluate if the xenobiotics studied develop stress oxidative in mice brain. HO activity was 50-70% induced after chronic Enflurane and Isoflurane anaesthesia, dietary Griseofulvin and starvation. An increase in mRNA HO expression was caused by chronic anaesthesia and Veronal treatments; instead allylisopropilacetamide (AIA) reduced mRNA expression. ALA-S activity was induced by acute administration of anaesthetics (89%), veronal (240%) and ethanol (80%), while ALA-S mRNA expression augmented by chronic administration of enflurane, AIA and veronal. Stress markers such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities and malondialdehyde and reduced glutathione levels showed different responses depending on the xenobiotic assayed. In conclusion, some of the drugs studied produced oxidative stress in brain that was confirmed through HO induction and this could be one of the factors leading to porphyric neuropathy.
Rodriguez
J A
JA
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP-CONICET), Facultad de Ciencias Exactas y Naturales, University of Buenos Aires, Argentina.
Martinez
M del C
Mdel C
Gerez
E
E
Batlle
A
A
Buzaleh
A M
AM
D000624:5-Aminolevulinate Synthetase; D000818:Animals; D000975:Antioxidants; D001462:Barbital / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D004737:Enflurane / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006118:Griseofulvin / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress; D017118:Porphyria, Acute Intermittent / Q000209:etiology; D011165:Porphyrinogens / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis
D000975:Antioxidants; D011165:Porphyrinogens; D012333:RNA, Messenger; D006118:Griseofulvin; D000431:Ethanol; D001462:Barbital; D004737:Enflurane; D007530:Isoflurane; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase