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Effects of acetaminophen on hepatic microcirculation in mice

BioMed Central
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DOI: 10.1186/1476-5926-2-s1-s33
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Abstract ral ss BioMed CentComparative Hepatology Open AcceProceedings Effects of acetaminophen on hepatic microcirculation in mice Yoshiya Ito*, Nancy W Machen, Edward R Abril and Robert S McCuskey Address: Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson, AZ, 85724-5044, USA Email: Yoshiya Ito* -; Nancy W Machen -; Edward R Abril -; Robert S McCuskey - * Corresponding author Introduction Acetaminophen (APAP) intoxication from overdosing can result in severe hepatic damage, which is characterized by hemorrhagic centrilobular necrosis and by towering the levels of transaminase. The APAP-induced hepatic necro- sis is preceded by centrilobular microvascular congestion thought to be due to collapse of the sinusoidal wall and the infiltration of blood elements into the space of Disse [1]. These findings suggest that, in addition to direct hepa- tocellular damage, sinusoidal endothelial cells (SECs) participate in liver injury elicited by APAP overdose. As a result, the present study was conducted to examine changes in hepatic microcirculation after APAP adminis- tration using in vivo microscopic methods. Methods APAP (600 mg/kg) was given to male C57Bl/6 mice by oral gavage. At 0, 0.5, 1, 2, 4, 6, 12 h after APAP, the hepatic microvascular responses in anesthetized animals were examined using established high resolution in vivo microscopic methods [2]. The relative adequacy of blood perfusion through the sinusoids was evaluated by count- ing the number of sinusoids containing blood flow (SCF) in ten periportal (PP) and ten centrilobular (CL) regions in each animal. To examine the interaction of leukocytes with the sinusoidal wall, the number of leukocytes adher- ing to the endothelial lining of sinusoids was counted. Endothelial swelling was assessed by counting the num- bers of swollen cells. Kupffer cell phagocytic

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