Abstract:
BACKGROUND & AIMS:High oxidative stress plays a major role in increasing hepatic vascular resistance in cirrhosis, by facilitating liver fibrosis and by increasing hepatic vascular tone. This study is aimed at investigating whether the use of the novel isoform of recombinant human manganese superoxide dismutase (rMnSOD) could be a new therapeutic strategy to reduce oxidative stress and portal hypertension in cirrhotic rats. METHODS:In CCl(4)- and BDL-cirrhotic rats treated with rMnSOD (i.p. 15 μg/kg/day) or its vehicle for 7 days, mean arterial pressure (MAP), portal pressure (PP) and portal blood flow (PBF) or small mesenteric arterial flow (SMABF) were measured. In addition, in CCl(4)-cirrhotic rats, we evaluated the hepatic vasodilatory response to acetylcholine, liver fibrosis with Sirius red staining and hepatic stellate cell activation by α-smooth muscle actin (α-SMA) protein expression. RESULTS:rMnSOD treatment significantly reduced PP either in CCl(4)- or BDL-cirrhotic rats without significant changes in splanchnic blood flow, suggesting a reduction in hepatic vascular resistance. MAP was not modified. Reduction in PP was associated with a significant reduction in liver fibrosis, and α-SMA protein expression as well as with improved vasodilatory response to acetylcholine. CONCLUSIONS:Chronic rMnSOD administration to cirrhotic rats reduces portal pressure by reducing hepatic vascular resistance without deleterious effects on systemic hemodynamics, suggesting that it might constitute a new antioxidant to be considered as additional therapy for treating portal hypertension in cirrhosis.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Guillaume M,Rodriguez-Vilarrupla A,Gracia-Sancho J,Rosado E,Mancini A,Bosch J,Garcia-Pagán JCdoi
10.1016/j.jhep.2012.09.010subject
Has Abstractpub_date
2013-02-01 00:00:00pages
240-6issue
2eissn
0168-8278issn
1600-0641pii
S0168-8278(12)00700-3journal_volume
58pub_type
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