Platelet-activating factor (PAF) and its relation to prostaglandins, leukotrienes and other aspects of arachidonate metabolism

Peplow, P.V.; Mikhailidis, DP

doi:10.1016/0952-3278(90)90057-r

Cited by 43 publications

(6 citation statements)

References 118 publications

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“…4 These pathways include activation of a GTPase that inhibits adenylate cyclases; stimulation of Ca 2 + stores and activation of phospholipases that yield diacyglycerol, inositol triphosphate and free arachidonic acid which can be acted upon through the cyclooxygenase and lipoxygenase pathways to give eicosanoids. 42 It is interesting and consistent with the above PAF receptor interaction hypothesis that the authors previously reported an inhibition of adenylate cyclase, 43 increased intracellular level of calcium, 44 increased lung phospholipase A2 activity 4s and increased plasma 46 and lung 4 levels of some eicosanoid in a bleomycin hamster model of pulmonary fibrosis.…”

Section: Discussionsupporting

confidence: 77%

Attenuation of amiodarone induced lung fibrosis and phospholipidosis in hamsters, by treatment with the platelet activating factor receptor antagonist, WEB 2086

Giri

Hyde

Haynam

et al. 1993

Mediators of Inflammation

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Therapeutic use of amiodarone (AMD), a Class III antiarrhythmic drug is complicated by the development of lung fibrosis (LF) and phospholipidosis (PL). In the present study, the effectiveness of a PAF antagonist, WEB 2086, against AMD induced LF and PL has been tested in hamsters. The animals were randomly divided into four groups: (1) saline + H2O; (2) WEB + H2O; (3) saline + AMD; and (4) WEB + AMD. Saline or WEB (10 mg/kg i.p.) was given 2 days prior to intratracheal instillation of water or AMD (1.5 μmol/0.25 ml/100 g BW) and thereafter daily throughout the study. Twenty-eight days after intratracheal instillation, the animals were killed and the lungs processed for various assays. The amount of lung hydroxyproline, an index of LF, in saline + H2O, WEB + H2O, saline + AMD, and WEB + AMD groups were 959 ± 46, 1035 ± 51, 1605 ± 85 and 1374 ± 69 μg/lung, respectively. Total lung PL, an index of phospholipidosis, in the corresponding groups were 8.4 ± 0.4, 8.3 ± 0.3, 11.7 ± 0.3 and 9.9 μg/lung. Lung malondialdehyde, an index of lipid peroxidation and superoxide dismutase activity in saline + H2O WEB + H2O, saline + AMD, and WEB + AMD were 93.0 ± 4.3, 93.0 ± 2.7, 138.9 ± 6.0 and 109.0 ± 3.8 nmol/lung and 359.7 ± 13.9, 394.0 ± 22.8, 497.5 ± 19.7 and 425.5 ± 4.9 units/lung, respectively. Administration of AMD alone caused significant increases in all the above indexes of lung toxicity, and treatment with WEB 2086 minimized the AMD induced toxicity as reflected by significant decreases in these indexes. Histopathological studies revealed a marked reduction in the extent and severity of lung lesions in the WEB + AMD group compared with the saline + AMD group. Treatment with WEB 2086 also reduced the acute mortality from 35% in saline + AMD group to 22% in WEB + AMD group. It was concluded that PAF is involved in the AMD induced lung fibrosis and phospholipidosis and that the PAF receptor antagonist may, therefore, be potentially useful in reducing AMD induced lung toxicity.

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Section: Discussionsupporting

confidence: 77%

Attenuation of amiodarone induced lung fibrosis and phospholipidosis in hamsters, by treatment with the platelet activating factor receptor antagonist, WEB 2086

Giri

Hyde

Haynam

et al. 1993

Mediators of Inflammation

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“…Arachidonic acid (20:4n-6) released by PLA2 is used for synthesis of eicosanoids, such as PGE2 and LTB4 by cyclooxygenase (COX) or lipoxygenase (18). Several studies demonstrate that increased production of eicosanoids, especially LTB4, during inflammation or caused by endotoxin is dependent on PAF concentration (17,32).…”

Section: Discussionmentioning

confidence: 99%

Dietary Ganglioside Inhibits Acute Inflammatory Signals in Intestinal Mucosa and Blood Induced by Systemic Inflammation of Escherichia Coli Lipopolysaccharide

Park¹,

Suh²,

Thomson³

et al. 2007

Shock

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Our previous study demonstrated that feeding ganglioside increased total ganglioside content while decreasing cholesterol and caveolin-1 content in developing rat intestinal lipid microdomains. Cholesterol or caveolin depletion in membranes inhibits inflammatory signaling by disrupting microdomain structure. We hypothesized that dietary ganglioside-induced reduction in cholesterol content will reduce proinflammatory mediators in the intestinal mucosa after acute exposure to bacterial endotoxin. Weanling rats were fed semipurified diets with 0.1% (wt/wt of total fat) gangliosides (treatment) or without ganglioside (control). After 2 weeks of feeding, half of animals from each diet group were injected with saline or lipopolysaccharide (LPS) endotoxin (Escherichia coli serotype O111:B4, intraperitoneal, 3 mg/kg body weight) to induce acute gut inflammation. Intestinal mucosa and blood were collected after 6 h. The effect of dietary ganglioside on proinflammatory mediators including cholesterol, platelet-activating factor, prostaglandin E2, leukotriene B4 (LTB4), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) was determined in inflamed mucosa and blood. Feeding animals the control diet increased cholesterol content in intestinal lipid microdomains by 92% after LPS injection compared with saline injection. Animals fed the ganglioside diet significantly decreased cholesterol content in lipid microdomains by 60% compared with animals fed the control diet. Feeding animals the ganglioside diet increased total ganglioside content by 90% while decreasing platelet-activating factor content by 45% in the inflamed mucosa by acute systemic exposure to LPS compared with animals fed the control diet. When animals were fed the ganglioside diet, the levels of prostaglandin E2, LTB4, IL-1beta, and TNF-alpha were lower in inflamed mucosa, and LTB4, IL-1beta, and TNF-alpha were decreased in plasma by 41%, 58%, and 55% compared with control animals, respectively. The present study demonstrates that dietary gangliosides inhibit proinflammatory signals in the intestine and blood induced by acute inflammation of LPS and suggests therapeutic potential in the treatment and management of acute local and systemic inflammatory diseases.

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“…PAF can stimulate platelet and leukocyte aggregation, promote oxygen free radical production, increase adhesion molecules, lead to white blood cell adhesion, and aggregate and increase oxygen radicals [45]. PAF can dilate blood vessels, increase vascular permeability, make plasma infiltration out, reduce the blood volume, cause extensive edema of the colonic mucosa [46], stimulate intestinal secretion induced diarrhea, and promote the release of prostaglandins and leukotrienes and other inflammatory reactions [47]. PAF and platelets activate each other, making active UC abnormal blood rheology and lead to thrombotic complications; PAF binds to surface receptors of target cell and activates nuclear factor NF- κ B, which upregulates the synthesis and secretion of TNF- α , IL-1 [48, 49].…”

Section: Discussionmentioning

confidence: 99%

Chlorogenic Acid Attenuates Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice through MAPK/ERK/JNK Pathway

Gao

Wang

et al. 2019

BioMed Research International

149

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Objective. Observe the protective effect of chlorogenic acid on dextran sulfate-induced ulcerative colitis in mice and explore the regulation of MAPK/ERK/JNK signaling pathway. Methods. Seventy C57BL/6 mice (half males and half females) were randomly divided into 7 groups, 10 in each group: control group (CON group), UC model group (UC group), and sulfasalazine-positive control group (SASP group), chlorogenic acid low dose group (CGA-L group), chlorogenic acid medium dose group (CGA-M group), chlorogenic acid high dose group (CGA-H group), and ERK inhibitor + chlorogenic acid group (E+CGA group). The effects of chlorogenic acid on UC were evaluated by colon mucosa damage index (CMDI), HE staining, immunohistochemistry, ELISA, and Western blot. The relationship between chlorogenic acid and MAPK/ERK/JNK signaling pathway was explored by adding ERK inhibitor. Results. The UC models were established successfully by drinking DSS water. Chlorogenic acid reduces DSS-induced colonic mucosal damage, inhibits DSS-induced inflammation, oxidative stress, and apoptosis in colon, and reduces ERK1/2, p -ERK, p38, p-p38, JNK, and p-JNK protein expression. ERK inhibitor U0126 reversed the protective effect of chlorogenic acid on colon tissue. Conclusion. Chlorogenic acid can alleviate DSS-induced ulcerative colitis in mice, which can significantly reduce tissue inflammation and apoptosis, and its mechanism is related to the MAPK/ERK/JNK signaling pathway.

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Platelet-activating factor (PAF) and its relation to prostaglandins, leukotrienes and other aspects of arachidonate metabolism

Cited by 43 publications

References 118 publications

Attenuation of amiodarone induced lung fibrosis and phospholipidosis in hamsters, by treatment with the platelet activating factor receptor antagonist, WEB 2086

Attenuation of amiodarone induced lung fibrosis and phospholipidosis in hamsters, by treatment with the platelet activating factor receptor antagonist, WEB 2086

Dietary Ganglioside Inhibits Acute Inflammatory Signals in Intestinal Mucosa and Blood Induced by Systemic Inflammation of Escherichia Coli Lipopolysaccharide

Chlorogenic Acid Attenuates Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice through MAPK/ERK/JNK Pathway

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