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Liver Protection (liver + protection)

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Medical Sciences100%

Selected Abstracts

Tezosentan normalizes hepatomesenteric perfusion in a porcine model of cardiac tamponade

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2009
A. ÅNEMAN
Background: To investigate endothelin-1 (ET-1)-dependent hepatic and mesenteric vasoconstriction, and oxygen and lactate fluxes in an acute, fixed low cardiac output (CO) state. Methods: Sixteen anesthetized, mechanically ventilated pigs were studied. Cardiac tamponade was established to reduce portal venous blood flow (QPV) to 2/3 of the baseline value. CO, hepatic artery blood flow (QHA), QPV, hepatic laser-Doppler flow (LDF), hepatic venous and portal pressure, and hepatic and mesenteric oxygen and lactate fluxes were measured. Hepatic arterial (RHA), portal (RHP) and mesenteric (Rmes) vascular resistances were calculated. The combined ETA,ETB receptor antagonist tezosentan (RO 61-0612) or normal saline vehicle was infused in the low CO state. Measurements were made at baseline, after 30, 60, 90 min of tamponade, and 30, 60, 90 min following the infusion of tesozentan at 1 mg/kg/h. Results: Tamponade decreased CO, QPV, QHA, LDF, hepatic and mesenteric oxygen delivery, while hepatic and mesenteric oxygen extraction and lactate release increased. RHA, RHP and Rmes all increased. Ninety minutes after tesozentan, QPV, LDF and hepatic and mesenteric oxygen delivery and extraction increased approaching baseline values, but no effect was seen on CO or QHA. Hepatic and mesenteric handling of lactate converted to extraction. RHA, RHP and Rmes returned to baseline values. No changes were observed in these variables among control animals not receiving tesozentan. Conclusion: In a porcine model of acute splanchnic hypoperfusion, unselective ET-1 blockade restored hepatomesenteric perfusion and reversed lactate metabolism. These observations might be relevant when considering liver protection in low CO states. [source]

Liver injury and liver protection: mechanisms and novel treatment strategies

LIVER INTERNATIONAL, Issue 8 2006
ALEXANDER L. GERBES
[source]

Effect of the aqueous extract of Syzygium cumini on carbon tetrachloride-induced hepatotoxicity in rats

PHYTOTHERAPY RESEARCH, Issue 8 2007
Rafael Noal Moresco
Abstract The aim of this study was to evaluate the effect of the aqueous Syzygium cumini leaf extract, given either as a single dose or by 7 days of pretreatment, on hepatotoxicity induced by carbon tetrachloride in rats. Blood samples obtained after treatments were measured for aspartate aminotransferase (AST) and alanine aminotransferase (ALT). A significant increase in the AST and ALT activities occurred after carbon tetrachloride administration alone, which was significantly lowered by preadministration with the aqueous extract of Syzygium cumini, but not by a single dose. This suggests that the extract may be useful for liver protection but needs to be given over a significant period and prior to liver injury. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Disposition of WR-1065 in the liver of tumor-bearing rats following regional vs systemic administration of amifostine

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2004
Micha Levi
Abstract Purpose,Amifostine is a prodrug in which selectivity is largely determined by the preferential formation and uptake of its cytoprotective metabolite, WR-1065, in normal tissues as a result of differences in membrane-bound alkaline phosphatase activity. It was hypothesized that amifostine may be a good candidate for regional drug delivery to the liver because of its large hepatic extraction and total body clearance. Methods,Rat livers were implanted with Walker-256 tumors. The tumor-bearing rats received 15 min infusions of amifostine (200 mg/kg) via the portal vein or the femoral vein. WR-1065 concentrations in the blood, liver and tumor were measured at various times. Results,The WR-1065 tumor portal dosing AUC15,60 was 40% of systemic dosing, and tumor concentrations following portal dosing were one-fifth of that following systemic dosing. The portal dosing WR-1065 liver AUC15,60 was 60% higher than the values for systemic dosing. The liver/tumor concentration ratios of WR-1065 following portal dosing were up to 8-fold higher than the ratio following systemic administration. Unfortunately, systemic exposure to WR-1065 was greater following portal vs systemic amifostine. Conclusions,Amifostine may provide increased liver protection and decreased tumor protection from radio- or chemotherapy when administered by the portal vein. However, portal dosing also increases systemic exposure to WR-1065, which is associated with hypotension. Copyright © 2004 John Wiley & Sons, Ltd. [source]