Upregulation of endothelial nitric oxide synthase maintains nitric oxide production in the cerebellum of thioacetamide cirrhotic rats
Section snippets
Animals and cirrhotic experimental model
A total of 20 adult (200–250 g; 4-month-old) male Wistar rats were kept under standard conditions of light and temperature and allowed ad libitum access to a commercial rat chow. Half of these animals were given TAA in the drinking water (300 mg/ml for 97 days) to trigger hepatic cirrhosis (Torres et al., 1998), while the other half served as controls. To verify that the cirrhotic process and the neuronal injury characteristic of hepatogenic encephalopathy (Sarhan et al., 1993, Peeling et al.,
NOS isoform immunocytochemistry
Immunoreactivity (IR) of nNOS (nNOS-IR) in the cerebellar cortex is presented in Fig. 1A, B. Both control (Fig. 1A) and TAA-cirrhotic rats (Fig. 1B) showed nNOS-IR stellate and basket cells; however, basket-cell bodies and their processes surrounding Purkinje cell showed higher IR in TAA-cirrhotic than in control rats (insert in Fig. 1B). In addition, in the molecular layer the stellate-cell population appeared to have not only high IR but also a greater number of nNOS-IR cells in the TAA
Discussion
The results presented here reveal slight changes in the tissue and cellular distribution pattern of the nNOS, iNOS and nitrated proteins in the cerebellum of rats with TAA-induced cirrhosis. In addition, cirrhotic animals showed strong eNOS IR and NADPH-diaphorase activity in perivascular glial cells. Moreover, although neither nNOS nor iNOS cerebellar protein levels appeared to be significantly affected, the eNOS isoform augmented its expression and a trend of increased NO production took
Acknowledgements
This work was supported by Dirección General de Investigación Científica y Técnica (PM98-0126-CO2-02) and Junta de Andalucía (CVI-0184). Santos Blanco is a FPDeI grant holder from Junta de Andalucía. We thank Mr. David Nesbitt for his help in the manuscript preparation.
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2007, Brain ResearchCitation Excerpt :Peroxynitrite is a powerful oxidant that may cause cerebral damage either directly by interacting and destroying cell proteins, lipids and DNA or indirectly by interfering with cell signalling pathways and gene regulation (Traystman et al., 1991). Peroxynitrite may be detected in tissues because this molecule is capable of nitrating tyrosine protein residues to form nitrotyrosine complexes, these being good markers of the cumulative exposure to NO (Del Moral et al., 2004; Hernandez et al., 2004; Ischinopoulos and al-Mehdi, 1995). One of the main leading causes to peroxynitrite formation depends on the tissue-NO availability (Forman et al., 1998), and it also depends heavily on the type of NOS isoform involved in its synthesis.
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2005, Brain ResearchCitation Excerpt :Calcium dependent nNOS activity remained at low levels whereas eNOS increased after this time. This augment in eNOS activity can be a compensatory mechanism to balance NO production in the cerebellum to minimize gamma-irradiation injury as it was suggested by Hernandez et al. [24] in the cerebellum of thioacetamide cirrhotic rats. On the other hand, an increase in iNOS activity after 60 days post-irradiation was found.