INVESTIGADORES
BUZALEH Ana Maria
congresos y reuniones científicas
Título:
Porphyrinogenic agents and the haem protein nitric oxide synthase: changes inthe localizationof the isoform eNOS in the liver of mice.
Autor/es:
RUSPINI, SILVINA; MEISS, ROBERTO; LAVANDERA, JIMENA; BATLLE ALCIRA; BUZALEH, ANA MARIA
Lugar:
Cardiff
Reunión:
Congreso; International Porphyrins and Porphyrias Meeting; 2011
Institución organizadora:
British Journal of Dermatologists
Resumen:
Hepatic porphyrias lead to liver damage. The existence of
haem as a functional group in a large variety of housekeeping
proteins is crucial for life and death. Under haem-deficiency
conditions, cells fail to survive and subsequently die because of impairment of major vital functions carried out by haem
proteins. Nitric oxide (NO) synthase (NOS) is the enzyme
responsible for NO synthesis in mammalian tissues. Four NOS
isoforms have been described: neuronal NOS (nNOS), endothelial
NOS (eNOS), inducible NOS (iNOS) and mitochondrial
NOS (mtNOS). The administration of volatile anaesthetics and
other porphyrinogenic agents produces alterations in the activity
and expression of NOS in the brain and liver of mice. We
also previously observed changes in the localization of nNOS
and mtNOS due to these agents in the liver of mice. The aim
of this work was to investigate if porphyrinogenic agents also
produce any alteration in the localization of the isoform
eNOS. For this purpose livers from mice treated with volatile
anaesthetics such as Enflurane and Isoflurane and allylisopropylacetamide
(AIA) were removed and fixed in 10% neutralbuffered
formalin. Samples of hepatic lobules were processed
routinely and embedded in paraffin. At least six microtome
sections of 3?5 lm were stained with haematoxylin and eosin.
Immunohistochemistry was performed using the streptavidinbiotin-
peroxidase complex system LSAB (Dako, Glostrup, Denmark).
Acute anaesthetics administration produced an increase
in the staining intensity and the number of cells positive for
eNOS in the nuclei (50?75% vs. 10% in control group). In
the cytoplasm the results were different depending on the
anaesthetic studied, revealing a diminution of positive cells for
Enflurane (<10% vs. 25?50% in control group), while an
increase was observed for Isoflurane (25?50% vs. 25% in control
group). When these anaesthetics were administered
chronically no variation were detected in the staining intensity
of the expression but the number of cells positive for eNOS
increased in both cytoplasm (25?75% vs. 25% in control
group) and nuclei (25?50% vs. 10% in control group). In the
group receiving AIA, increases in intensity of expression and
in number of positive cells were also detected in both the
cytoplasm and the nuclei. These effects were not observed in
sinusoidal macrophages (von Kupffer cells) as a result of the
action of the xenobiotics studied. Liver NOS alterations
reported previously and here could affect the metabolic functions
of this organ and probably produce severe systemic
damage at the vascular level due to the deregulation of NO
synthesis.