Ethanol Binging Enhances Hepatic Microvascular Responses to Acetaminophen in Mice

Yoshiya, Ikuto; Abril, Edward R.; Bethea, Nancy W.; McCuskey, Robert S.

doi:10.1080/10739680490503456

Cited by 13 publications

(9 citation statements)

References 26 publications

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“…As above, the responses to 600 mg/kg APAP were most severe with administration of 300 mg/kg APAP to an ethanol binged animals eliciting nearly equal injury. These findings correlated with our recent findings obtained from in vivo microscopic studies that the area occupied by infiltration of erythrocytes in the Space of Disse is equal in mice treated 2 h after administration of a single dose of 600 mg/kg APAP [21] and after 300 mg/kg APAP following three weekly ethanol binges [30].…”

Section: Tem and Semsupporting

confidence: 90%

“…The formation of these gaps may be stimulated by the action of free radicals [33]. Our in vivo microscopic studies have shown that the oral gavage with APAP (300 mg/kg) in combination with ethanol binging caused infiltration of erythrocytes in the space of Disse at 2 h after APAP treatment, while the same dose of APAP alone failed to do this [30]. These results suggest that ethanol binging render SEC susceptible to APAP during an early phase of the toxicity.…”

Section: Discussionmentioning

confidence: 72%

“…Sinusoidal endothelial cells were isolated from 12 animals as described previously [30,31]. Briefly, the liver was perfused with a Collagenase type I solution for 2 min, broken apart and placed in a 250 ml flask containing a second solution of collagenase and shaken for 20 min at 37 8C.…”

Section: Sinusoidal Endothelial Cell Isolation and Cell Culturementioning

confidence: 99%

“…In another set of experiments, hepatic total glutathione (GSH) was determined colorimetrically using a commercially available kit (Oxford Biomedical Research, Oxford, MI) as described previously [30].…”

Section: Gsh Assaymentioning

confidence: 99%

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Ethanol binging exacerbates sinusoidal endothelial and parenchymal injury elicited by acetaminophen

McCuskey¹,

Bethea²,

Wong³

et al. 2005

Journal of Hepatology

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Section: Tem and Semsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 72%

Section: Sinusoidal Endothelial Cell Isolation and Cell Culturementioning

confidence: 99%

Section: Gsh Assaymentioning

confidence: 99%

See 2 more Smart Citations

Ethanol binging exacerbates sinusoidal endothelial and parenchymal injury elicited by acetaminophen

McCuskey¹,

Bethea²,

Wong³

et al. 2005

Journal of Hepatology

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“…This drug in an overdose (i.e., at doses that are different from analgesic doses that are safely and effectively used therapeutically) can induce severe hepatotoxicity in experimental animals and humans [13–15]. In our work, hepatotoxicity was reflected by a marked elevation of the levels of serum marker enzymes (AST, ALT, and ALP), increased MPO activity, and histopathologic alterations.…”

Section: Discussionmentioning

confidence: 63%

Hepatoprotective Effect of Pretreatment with Thymus vulgaris Essential Oil in Experimental Model of Acetaminophen‐Induced Injury

Grespan

Aguiar

Giubilei

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Acute liver damage caused by acetaminophen overdose is a significant clinical problem and could benefit from new therapeutic strategies. Objective. This study investigated the hepatoprotective effect of Thymus vulgaris essential oil (TEO), which is used popularly for various beneficial effects, such as its antiseptic, carminative, and antimicrobial effects. The hepatoprotective activity of TEO was determined by assessing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in mice. Their livers were then used to determine myeloperoxidase (MPO) enzyme activity and subjected to histological analysis. In vitro antioxidant activity was evaluated by assessing the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH•)-scavenging effects of TEO and TEO-induced lipid peroxidation. TEO reduced the levels of the serum marker enzymes AST, ALT, and ALP and MPO activity. The histopathological analysis indicated that TEO prevented acetaminophen-induced necrosis. The essential oil also exhibited antioxidant activity, reflected by its DPPH radical-scavenging effects and in the lipid peroxidation assay. These results suggest that TEO has hepatoprotective effects on acetaminophen-induced hepatic damage in mice.

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The Hepatic Microvascular System in Health and Its Response to Toxicants

McCuskey

2008

The Anatomical Record

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109

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This review briefly summarizes what is known about the dynamic morphology of the hepatic microvascular system that includes all vessels in the liver with a diameter less than 300 mm and various morphological sites within these vessels that regulate the distribution of blood flow. The latter include the various segments of the afferent portal venules and hepatic arterioles, the sinusoids, and central and hepatic venules. Sinusoids are unique exchange vessels lined by fenestrated endothelial cells which have important endocytotic functions and phagocytic Kupffer cells which are important for host defense. These are encircled by extraluminal stellate cells that are specialized pericytes containing fat droplets that store vitamin A. The principle sites for regulating blood flow are in the sinusoidal network with stellate and endothelial cells playing a major role in regulating the diameters of sinusoids and the distribution of blood flow in individual sinusoids, lobules, or segments of lobules. The sinusoidal endothelial cells are a sensitive and early target for several toxicants. For example, as early as 30 minutes after the administration of acetaminophen, the endothelial cells become swollen and begin to lose the ability to endocytose ligands. Within 2 hr, gaps through the cytoplasm appear formed by the destruction and/or coalescence of fenestrae which permit red blood cells to penetrate into the space of Disse. Subsequently, the sinusoid may collapse or disintegrate reducing blood flow. Anat Rec, 291:661-671,

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Ethanol Binging Enhances Hepatic Microvascular Responses to Acetaminophen in Mice

Abstract: These results suggest that ethanol binging increases APAP-induced liver injury by exacerbating infiltration of the Disse space with blood cells. Kupffer cells exert a protective role in the liver against APAP intoxication following ethanol binging.

Cited by 13 publications

References 26 publications

Ethanol binging exacerbates sinusoidal endothelial and parenchymal injury elicited by acetaminophen

Ethanol binging exacerbates sinusoidal endothelial and parenchymal injury elicited by acetaminophen

Hepatoprotective Effect of Pretreatment with Thymus vulgaris Essential Oil in Experimental Model of Acetaminophen‐Induced Injury

The Hepatic Microvascular System in Health and Its Response to Toxicants

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