INVESTIGADORES
VATTA Marcelo Sergio
congresos y reuniones científicas
Título:
Role of Endothelin 3 (ET3) in Estradiol 17B-glucuronide (E217G)-induced Cholestasis in the Rat
Autor/es:
RODRIGUEZ M; MARTINEFSKI M; TRIPODI V; VATTA MS; BIANCIOTTI LG
Lugar:
BOSTON, MA
Reunión:
Congreso; EXPERIMENTAL BIOLOGY 2015; 2015
Institución organizadora:
Federation of American Societies for Experimental Biology
Resumen:
We
previously reported that ET3 induces choleresis through ETB receptors coupled
to nitric oxide (NO). It enhances, independently of hemodynamic changes, bile
acid dependent and independent bile flows and promotes plasma membrane
insertion of the main hepatic transporters involved in bile genesis and
increases their mRNA expression (Clin Sci., 125:531, 2013). In this work
we aimed to determine whether ET3 played a beneficial role in E217G-induced
cholestasis. Sprague-Dawley rats were infused with ET3 (5 ng/kg/min) or vehicle
for 30 min followed by E217G administration to induce cholestasis. Bile samples
were collected every 5 min for 120 min. Bile acids were assessed in bile by
capillary electrophoresis. Other set of animals were also pretreated with
L-NAME (NO synthases inhibitor) or BQ788 (ETB receptor antagonist) before ET3
and E217G administration. ET3 prevented E217G-induced cholestasis and the
response was abolished by BQ788 or L-NAME. Furthermore ET3 also modified bile
acid excretion, particularly ursodeoxycholic acid and lithocholic acid as
compared with control and E217G. ET3 induced no changes in plasma
transaminases, bilirubin, alkaline phosphatase or 5´nucleotidase or in the
hepatic histology assessed by light microscopy in stained hematoxylin and eosin
liver samples. Present findings show that ET3 through ETB receptors
coupled to NO prevents E217G-induced cholestasis and modifies bile acid profile
excretion in the rat. Results further suggest that the ETB receptor
may represent a promising therapeutic target in pathophysiological situations
where bile flow is impaired.