Mice Brain Nitric Oxide Synthase Response Induced by Anaesthetics and Other Porphyrinogenic Drugs

Jimena      Lavandera; Alcira      Batlle; Ana      Maria Buzaleh

doi:10.2174/187231211794455271

Abstract

Porphyrias neuropathophysiology could be related to low levels of heme as a cofactor for nitric oxide synthase (NOS). We examined how anaesthetics and other porphyrinogenic agents affect mice NOS activity and expression. Brain response was differential depending on the cellular fraction analyzed. Most of the drugs diminished cytosolic activity. Instead, isoflurane, enflurane and ethanol increased mitochondrial activity. NOS expression also depended on the drug tested. A comparative study was performed in liver. Our present and previous results indicate the widespread action of porphyrinogenic agents in brain, which could be the reason why it is difficult to establish the onset of acute porphyria neurological manifestations.

Keywords: Anaesthetics, brain, nitric oxide synthase, porphyric neuropathy, porphyrinogenic agent, Porphyrias, neuropathophysiology, cytosolic activity, isoflurane, enflurane, ethanol, L-arginine, heme, tissue homeostasis, central nervous system, 5-Aminolevulinic acid, porphyrins, allylisopropylacetamide (AIA), sodium 5,5-diehylbarbiturate, griseofulvin (Gris), M mannitol, Homogenates, enzyme cytosolic fraction source, oxyhemoglobin, methemoglobin, superoxide dismutase, dithiothreitol, spectrophotometer, phenylmethylsulphonyl fluoride, leupeptin, pepstatin A, bovine serum, Santa Cruz Biotechnology, Western blot analysis, amino terminus, veronal, xenobiotics, mitochon-drial fraction, heme oxygenase, carbon monoxide, per-oxynitrite, nitrosative stress, immunohisto-chemistry