Effects of Pringle maneuver and partial hepatectomy on the pharmacokinetics and blood-brain barrier permeability of sodium fluorescein in rats.
Liver diseases are known to affect the function of remote organs. The aim of the present study was to investigate the effects of Pringle maneuver, which results in hepatic ischemia-reperfusion (IR) injury, and partial hepatectomy (Hx) on the pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a widely used marker of blood-brain barrier (BBB) permeability. Rats were subjected to Pringle maneuver (total hepatic ischemia) for 20 min with (HxIR) or without (IR) 70% hepatectomy. Sham-operated animals underwent laparotomy only. After 15 min or 8h of reperfusion, a single 25-mg/kg dose of FL was injected intravenously and serial (0-30 min) blood and bile and terminal brain samples were collected. Total and free (ultrafiltration) plasma, total brain homogenate, and bile concentrations of FL and/or its glucuronidated metabolite (FL-Glu) were determined by HPLC. Both IR and HxIR caused significant reductions in the biliary excretions of FL and FL-Glu, resulting in significant increases in the plasma AUC of the marker. Additionally, the free fraction of FL in plasma was significantly increased by HxIR. Although the brain concentrations of FL were increased by almost twofold in both IR and HxIR animals, the brain concentrations corrected by the free FL AUC (and not the total AUC) were similar in both groups at either time points. It is concluded that Pringle maneuver and/or partial hepatectomy substantially alters the hepatobiliary disposition, plasma AUC, plasma free fraction, and brain accumulation of FL without altering the BBB permeability to the marker.
['Miah|Mohammad K|MK|', 'Shaik|Imam H|IH|', 'Bickel|Ulrich|U|', 'Mehvar|Reza|R|']
D000255:Adenosine Triphosphate D000418:Albumins D000818:Animals D019540:Area Under Curve D001646:Bile D001647:Bile Acids and Salts D001812:Blood-Brain Barrier D002851:Chromatography, High Pressure Liquid D004195:Disease Models, Animal D019793:Fluorescein D006498:Hepatectomy D019194:Ischemic Preconditioning D008099:Liver D008102:Liver Circulation D008297:Male D026901:Membrane Transport Proteins D027361:Organic Anion Transporters D051381:Rats D017207:Rats, Sprague-Dawley D000637:Transaminases
Pringle maneuver Partial hepatectomy Pharmacokinetics Sodium fluorescein Blood–brain barrier permeability Hepatic ischemia–reperfusion injury