The Measurement of Platelet Aggregation and ATP-Release in Mice with Liver Damage Induced by Carbon Tetrachloride (CCl4) Using a Whole Blood Aggregometer

Okazaki, Masako; Zhang, Lisha; Sakamoto, Koji

doi:10.1254/jjp.48.407

Cited by 5 publications

(3 citation statements)

References 22 publications

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“…To examine whether HPS3 −/− mice retained normal reactivity to ADP (another dense granule marker) we measured platelet aggregation. When stimulated with ADP doses that do not induce secretion in wild-type HPS3 +/+ platelets,22 HPS3 −/− platelets showed equivalent aggregation (Fig. 1A–C) indicating that responsiveness to ADP was retained.…”

Section: Resultsmentioning

confidence: 95%

Platelet Dense-Granule Secretion Plays a Critical Role in Thrombosis and Subsequent Vascular Remodeling in Atherosclerotic Mice

et al. 2009

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Background— Platelet aggregation plays a critical role in myocardial infarction and stroke; however, the role of platelet secretion in atherosclerotic vascular disease is poorly understood. Therefore, we examined the hypothesis that platelet dense-granule secretion modulates thrombosis, inflammation, and atherosclerotic vascular remodeling after injury. Methods and Results— Functional deletion of the Hermansky-Pudlak syndrome 3 gene (HPS3 −/− ) markedly reduces platelet dense-granule secretion. HPS3 −/− mice have normal platelet counts, platelet morphology, and α-granule number, as well as maximal secretion of the α-granule marker P-selectin; however, their capacity to form platelet-leukocyte aggregates is significantly reduced ( P <0.05). To examine the role of platelet dense-granule secretion in these processes, atherosclerosis-prone mice with combined genetic deficiency of apolipoprotein E and HPS3 (ApoE −/− , HPS3 −/− ) were compared with congenic, atherosclerosis-prone mice with normal platelet secretion (ApoE −/− , HPS3 +/+ ). After 16 to 18 weeks on a high-fat diet, both groups of mice had similar fasting cholesterol levels and body weight. Carotid arteries of ApoE −/− , HPS3 +/+ mice thrombosed rapidly after FeCl 3 injury, but ApoE −/− , HPS3 −/− mice were completely resistant to thrombotic arterial occlusion ( P <0.01). Three weeks after injury, neointimal hyperplasia (from α-smooth muscle actin–positive cells) was significantly less ( P <0.001) in arteries from ApoE −/− , HPS3 −/− mice. In ApoE −/− , HPS3 −/− mice, there were also pronounced reductions in arterial inflammation, as indicated by a 74% decrease in CD45-positive leukocytes ( P <0.01) and a 73% decrease in Mac-3–positive macrophages ( P <0.05). Conclusions— In atherosclerotic mice, reduced platelet dense-granule secretion is associated with marked protection against the development of arterial thrombosis, inflammation, and neointimal hyperplasia after vascular injury.

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Section: Resultsmentioning

confidence: 95%

Platelet Dense-Granule Secretion Plays a Critical Role in Thrombosis and Subsequent Vascular Remodeling in Atherosclerotic Mice

et al. 2009

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“…We have already reported there were decreases of coagulative and fibrinolytic activities in CC14 induced liver injury (23). In addition, the activities of platelet aggregation by ADP and collagen were also suppressed in this liver injury (24). Therefore, the decrease in RES phagocytosis in CC14 induced liver injury is due to these suppressive effects.…”

Section: Discussionmentioning

confidence: 66%

Function of reticuloendothelial system on ethionine induced liver injury in mice.

1987

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Abstract-Phagocytic activity as a function of the reticuloendothelial system (RES) has been studied in ethionine induced liver injury by using the carbon clearance test. Liver damage in male and female mice was induced by DL and L-ethionine injections (1000 mg/kg/day, i.p.). In both female and male mice, a single dose or three injections of DL or L-ethionine caused increases in liver/body weight ratio, A/G ratio, GOT and GPT levels, and BSP retention.There was the decrease of the total protein levels in the serum.The degree of liver injury was more severe after three injections of DL and L-ethionine than after a single injection of them.After a single injection of ethionine, the L-isomer induced a slightly greater response than the racemic mixture, except for BSP retention.On the other hand, phagocytic activities by the carbon clearance test were increased after a single injection or three injections of DL and L-ethionine.That is, the K value was increased in all ethionine treated mice except for females with three injections of DL-ethionine. The a value was increased after three injections in DL and L-ethionine treated males and DL-ethionine treated females.In addition, the increase in carbon uptake by Kupffer cells can be seen by light microscopy after a single injection or three injections of DL or L-ethionine.These findings indicate that ethionine injections induce the enhancement of RES phagocytosis, although the biochemical parameters indicating liver injury are changed severely. These results support the data indicating no correlation between the alteration of RES activity and the degree of liver injury.

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“…At present, studies on the hepatotoxicity of combined exposure to ethanol and carbon tetrachloride are the most comprehensive . CCl 4 is commonly accepted as a typical toxicant, and CCl 4 ‐induced liver injury was a classic model of chemical liver toxicity . After entering the body, CCl 4 is metabolized by the liver microsomal CYP450, generating active trichloromethyl free radicals and stimulating the chain reaction of oxidation of phospholipid molecules in the cell, thereby disrupting cell membrane structure and function.…”

Section: Discussionmentioning

confidence: 99%

Toxic effects of combined treatment of 1,2‐dichloroethane and ethanol on mouse brain and the related mechanisms

Zhang

Jin

2019

J Biochem & Molecular Tox

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The aim of this study was to explore the mechanisms of brain damage induced by the combined treatment of mice with 1,2-dichloroethane (1,2-DCE) and ethanol. Mice were divided into control group; 1,2-DCE-intoxicated group; ethanol-treated group; and low-, medium-, and high-dose combined treatment groups. Histological observations along with brain organ coefficients and water content were used to measure the brain damage directly and indirectly. The levels of nonprotein sulfhydryls, malondialdehyde (MDA), and superoxide dismutase activity were used as parameters to evaluate oxidative stress in the brain. Protein and messenger RNA (mRNA) levels of cytochrome P450 2E1 (CYP2E1), zonula occludens-1 (occludin and zo-1), aquaporin-4 (AQP4), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase (HO)-1, and the γ-glutamyl cysteine synthetase catalytic and modulatory subunits (γ-GCSc, GR, and γ-GCSm) in the brain were examined by Western blot analysis and quantitative polymerase chain reaction analysis, respectively. Effects of the combined treatment of 1,2-DCE and ethanol were evaluated by analysis of variance with a factorial design. The results suggested that combined exposure to ethanol and 1,2-DCE synergistically increased CYP2E1 protein and mRNA levels, accelerated the metabolism of ethanol and 1,2-DCE in the brain tissue, induced high production of reactive oxygen species (ROS), and increased MDA levels, thereby damaging the blood-brain barrier and causing obvious pathological changes in brain tissue. However, the increased level of ROS activated the Nrf2 signal transduction pathway, promoting the expression of HO-1 and glutathione-related antioxidant enzymes in the brain to protect the cells from oxidative damage.

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The Measurement of Platelet Aggregation and ATP-Release in Mice with Liver Damage Induced by Carbon Tetrachloride (CCl4) Using a Whole Blood Aggregometer

Cited by 5 publications

References 22 publications

Platelet Dense-Granule Secretion Plays a Critical Role in Thrombosis and Subsequent Vascular Remodeling in Atherosclerotic Mice

Platelet Dense-Granule Secretion Plays a Critical Role in Thrombosis and Subsequent Vascular Remodeling in Atherosclerotic Mice

Function of reticuloendothelial system on ethionine induced liver injury in mice.

Toxic effects of combined treatment of 1,2‐dichloroethane and ethanol on mouse brain and the related mechanisms

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