scholarly journals Lipid Droplet Accumulation and Impaired Fat Efflux in Polarized Hepatic Cells: Consequences of Ethanol Metabolism

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Benita L. McVicker ◽  
Karuna Rasineni ◽  
Dean J. Tuma ◽  
Mark A. McNiven ◽  
Carol A. Casey
Keyword(s):  
Lipid Droplets ◽  
Human Fibroblasts ◽  
Ethanol Metabolism ◽  
Ethanol Treatment ◽  
Alcohol Metabolism ◽  
Hepatic Cells ◽  
Lipid Efflux ◽  
Associated Proteins ◽  
Dose Dependent Increase ◽  
Dose Dependent

Steatosis, an early manifestation in alcoholic liver disease, is associated with the accumulation of hepatocellular lipid droplets (LDs). However, the role ethanol metabolism has in LD formation and turnover remains undefined. Here, we assessed LD dynamics following ethanol and oleic acid treatment to ethanol-metabolizing WIF-B cells (a hybrid of human fibroblasts (WI 38) and Fao rat hepatoma cells). An OA dose-dependent increase in triglyceride and stained lipids was identified which doubled (P<0.05) in the presence of ethanol. This effect was blunted with the inclusion of an alcohol metabolism inhibitor. The ethanol/ OA combination also induced adipophilin, LD coat protein involved in the attenuation of lipolysis. Additionally, ethanol treatment resulted in a significant reduction in lipid efflux. These data demonstrate that the metabolism of ethanol in hepatic cells is related to LD accumulation, impaired fat efflux, and enhancements in LD-associated proteins. These alterations in LD dynamics may contribute to ethanol-mediated defects in hepatocellular LD regulation and the formation of steatosis.

scholarly journals Stimulation of sulphated glycosaminoglycan and decorin production in adult dermal fibroblasts by recombinant human interleukin-4

1995 ◽  
Vol 307 (3) ◽  
pp. 673-678 ◽  
Author(s):  
Y Wegrowski ◽  
V Paltot ◽  
P Gillery ◽  
B Kalis ◽  
A Randoux ◽  
...  
Keyword(s):  
Culture Medium ◽  
Core Protein ◽  
Human Fibroblasts ◽  
Inflammatory Cells ◽  
Dermal Fibroblasts ◽  
Interleukin 4 ◽  
Proteoglycan Synthesis ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Sulphated Glycosaminoglycan

Interleukin-4 (IL-4) is a pleiotropic cytokine expressed by inflammatory cells. Previous work from our laboratory has shown that it stimulates collagen synthesis in fibroblasts. Here we report the effects of recombinant human IL-4 on glycosaminoglycan (GAG) and proteoglycan synthesis in normal dermal fibroblasts from adult donors. IL-4 (10 and 100 units/ml) induced a dose-dependent increase of [3H]glucosamine and [35S]sulphate incorporation into total GAGs. The analysis of the different GAG fractions indicated the enhanced synthesis of dermatan/chondroitin sulphates. IL-4 had no effect on hyaluronan synthesis. The increase of sulphated GAG synthesis was correlated with an increase of proteoglycans in the culture medium. Decorin was identified as the major chondroitin/dermatan sulphate-containing proteoglycan in the culture medium of fibroblasts. Its synthesis was strongly stimulated by IL-4. Both the core-protein synthesis and mRNA expression were enhanced, indicating that the cytokine acted, at least in part, at the pre-translational level. These results indicate that IL-4 is able to modulate not only collagen, but also proteoglycan, production by human fibroblasts. Their implications in physiopathological processes such as wound healing or fibrosis is suggested.

scholarly journals Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant ALDH2*2 Gene Allele

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1183
Author(s):  
Yi-Chyan Chen ◽  
Li-Fang Yang ◽  
Ching-Long Lai ◽  
Shih-Jiun Yin
Keyword(s):  
Self Control ◽  
Sociocultural Factors ◽  
Alcohol Metabolism ◽  
Alcohol Sensitivity ◽  
Young Males ◽  
Subjective Perceptions ◽  
Biological Determinants ◽  
Drinking Behaviors ◽  
Dose Dependent Increase ◽  
Dose Dependent

Alcoholism is a complex behavior trait influenced by multiple genes as well as by sociocultural factors. Alcohol metabolism is one of the biological determinants that can significantly influence drinking behaviors. Alcohol sensitivity is thought to be a behavioral trait marker for susceptibility to develop alcoholism. The subjective perceptions would be an indicator for the alcohol preference. To investigate alcohol sensitivity for the variants ADH1B*2 and ALDH2*2, sixty healthy young males with different combinatory ADH1B and ALDH2 genotypes, ADH1B*2/*2–ALDH2*1/*1 (n = 23), ADH1B*2/*2–ALDH2*1/*2 (n = 27), and ADH1B*1/*1–ALDH2*1/*1 (n = 10), participated in the study. The subjective perceptions were assessed by a structured scale, and blood ethanol and acetaldehyde were determined by GC and HPLC after an alcohol challenge in two dose sessions (0.3 g/kg or 0.5 g/kg ethanol). The principal findings are (1) dose-dependent increase of blood ethanol concentration, unaffected by ADH1B or ALDH2; (2) significant build-up of blood acetaldehyde, strikingly influenced by the ALDH2*2 gene allele and correlated with the dose of ingested alcohol; (3) the increased heart rate and subjective sensations caused by acetaldehyde accumulation in the ALDH2*2 heterozygotes; (4) no significant effect of ADH1B polymorphism in alcohol metabolism or producing the psychological responses. The study findings provide the evidence of acetaldehyde potentiating the alcohol sensitivity and feedback to self-control the drinking amount. The results indicate that ALDH2*2 plays a major role for acetaldehyde-related physiological negative responses and prove the genetic protection against development of alcoholism in East Asians.

Increased Expression of u-PA and u-PAR on Monocytes by LDL and Lp(a) Lipoproteins – Consequences for Plasmin Generation and Monocyte Adhesion

1999 ◽  
Vol 81 (04) ◽  
pp. 594-560 ◽  
Author(s):  
Florence Ganné ◽  
Marc Vasse ◽  
Jean-Louis Beaudeu ◽  
Jacqueline Peynet ◽  
Arnaud François ◽  
...  
Keyword(s):  
Fold Increase ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Atheromatous Plaque ◽  
Monocyte Adhesion ◽  
Blood Monocytes ◽  
Proteolytic Cascade ◽  
Ecm Degradation ◽  
Dose Dependent Increase ◽  
Dose Dependent

SummaryMonocyte-derived foam cells figure prominently in rupture-prone regions of atherosclerotic plaque. As urokinase/urokinase-receptor (u-PA/u-PAR) is the trigger of a proteolytic cascade responsible for ECM degradation, we have examined the effect of atherogenic lipoproteins on monocyte surface expression of u-PAR and u-PA. Peripheral blood monocytes, isolated from 10 healthy volunteers, were incubated with 10 to 200 µg/ml of native or oxidised (ox-) atherogenous lipoproteins for 18 h and cell surface expression of u-PA and u-PAR was analysed by flow cytometry. Both LDL and Lp(a) induced a dose-dependent increase in u-PA (1.6-fold increase with 200 μg/ml of ox-LDL) and u-PAR [1.7-fold increase with 200 μg/ml of ox-Lp(a)]. There is a great variability of the response among the donors, some of them remaining non-responders (absence of increase of u-PA or u-PAR) even at 200 μg/ml of lipoproteins. In positive responders, enhanced u-PA/u-PAR is associated with a significant increase of plasmin generation (1.9-fold increase with 200 μg/ml of ox-LDL), as determined by an amidolytic assay. Furthermore, monocyte adhesion to vitronectin and fibrinogen was significantly enhanced by the lipoproteins [respectively 2-fold and 1.7-fold increase with 200 μg/ml of ox-Lp(a)], due to the increase of u-PAR and ICAM-1, which are receptors for vitronectin and fibrinogen. These data suggest that atherogenous lipoproteins could contribute to the development of atheromatous plaque by increasing monocyte adhesion and trigger plaque weakening by inducing ECM degradation.

LH-RH TEST IN 100 PATIENTS WITH OVARIAN INSUFFICIENCY

1974 ◽  
Vol 75 (3) ◽  
pp. 428-434 ◽  
Author(s):  
P.-J. Czygan ◽  
M. Breckwoldt ◽  
F. Lehmann ◽  
R. Langefeld ◽  
G. Bettendorf
Keyword(s):  
Intravenous Injection ◽  
Functional State ◽  
Clear Correlation ◽  
Normal Range ◽  
Ovarian Insufficiency ◽  
Lh Rh ◽  
Dose Dependent Increase ◽  
Dose Dependent

ABSTRACT The effect of synthetic LH-RH was studied in 100 patients with various types of ovarian insufficiency by following up the FSH- and LH-levels in plasma. LH-RH was administered in doses of 12.5, 25 and 100 μg as a rapid intravenous injection. The patients were classified according to the endocrine state of the pituitary as evidenced by the urinary gonadotrophin levels. A clear correlation between the functional state of the pituitary and its responsiveness to exogenous LH-RH was demonstrated. Most of the patients with undetectable low urinary gonadotrophin levels failed to respond. The majority of patients with gonadotrophin excretion in the normal range and those with elevated levels reacted with a dose dependent increase in circulating LH. The amount of liberated FSH however was related to the injected dose only in patients with high gonadotrophic excretion. The present study indicates that synthetic LH-RH provides a useful tool in the evaluation of the pitutiary function particularly in patients with low and with undetectable gonadotrophin excretion. The data presented in this paper also demonstrate that the functional state of the pituitary is clearly reflected by the urinary gonadotrophin levels.

Evaluation of the Laxative activity of Saponin Enriched Hydroethanolic Pericarp extract of Sapindus emarginatus in Animal models

2020 ◽  
Vol 16 ◽  
Author(s):  
Lalitha Vivekanandan ◽  
Roxanne Gekonge Mandere ◽  
Sivakumar Thangavel
Keyword(s):  
Animal Models ◽  
Gravimetric Analysis ◽  
Triterpene Saponins ◽  
Laxative Effect ◽  
Saponin Content ◽  
The Family ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Efficacious Drug

Background: Constipation is a common, predominant, chronic gastrointestinal functional disorder. The drugs available to treat constipation are limited because of their side effects in long term use. So we need of efficacious drug to treat constipation. Sapindus emarginatus Vahl belongs to the family Sapindaceae, commonly known as soapnut. Traditionally used for the antipruritic, antifertility, constipation, and anti-inflammatory agents. Objective: The present study was undertaken to evaluate the laxative activity of hydroethanolic pericarp extract of Sapindus emarginatus (HESE) in animal models. Methods: The saponin content in extract was measured by gravimetric analysis. The laxative activity of hydroethanolic pericarp extract of Sapindus emarginatus is evaluated by the weight of feces matter, charcoal meal hyperperistalsis test, and loperamide induced constipation model. Results: The saponin content of the soapnut pericarp was 13.48 % and the extract was found to be 11.92 %. The results obtained from these models showed a significant dose-dependent increase in fecal weight, peristalsis index, and moisture content compared to control animals. Conclusion: The present study concluded that the oral administration of HESE showed a significant laxative activity by using different animal models. The presence of triterpene saponins is responsible for this activity. Further studies are needed to confirm their mechanism behind the laxative effect. The administration of extract was found to be a valid candidate in constipation therapy.

scholarly journals Fatty alcohol metabolism in cultured human fibroblasts. Evidence for a fatty alcohol cycle.

1987 ◽  
Vol 262 (36) ◽  
pp. 17412-17419 ◽  
Author(s):  
W B Rizzo ◽  
D A Craft ◽  
A L Dammann ◽  
M W Phillips
Keyword(s):  
Fatty Alcohol ◽  
Human Fibroblasts ◽  
Alcohol Metabolism ◽  
Cultured Human Fibroblasts

scholarly journals Morphological and Behavioral Effects in Zebrafish Embryos after Exposure to Smoke Dyes

Toxics ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 9
Author(s):  
Kimberly T. To ◽  
Lindsey St. Mary ◽  
Allyson H. Wooley ◽  
Mitchell S. Wilbanks ◽  
Anthony J. Bednar ◽  
...  
Keyword(s):  
Dose Dependence ◽  
Behavioral Effects ◽  
Zebrafish Embryos ◽  
Comprehensive Understanding ◽  
Anthraquinone Dyes ◽  
Locomotor Movement ◽  
Different Types ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Significant Mortality

Solvent Violet 47 (SV47) and Disperse Blue 14 (DB14) are two anthraquinone dyes that were previously used in different formulations for the production of violet-colored smoke. Both dyes have shown potential for toxicity; however, there is no comprehensive understanding of their effects. Zebrafish embryos were exposed to SV47 or DB14 from 6 to 120 h post fertilization (hpf) to assess the dyes’ potential adverse effects on developing embryos. The potential ability of both dyes to cross the blood–brain barrier was also assessed. At concentrations between 0.55 and 5.23 mg/L, SV47 showed a dose-dependent increase in mortality, jaw malformation, axis curvature, and edemas. At concentrations between 0.15 and 7.54 mg/L, DB14 did not have this same dose-dependence but had similar morphological outcomes at the highest doses. Nevertheless, while SV47 showed significant mortality from 4.20 mg/L, there was no significant mortality on embryos exposed to DB14. Regardless, decreased locomotor movement was observed at all concentrations of DB14, suggesting an adverse neurodevelopmental effect. Overall, our results showed that at similar concentrations, SV47 and DB14 caused different types of phenotypic effects in zebrafish embryos.

Increased Urinary Excretion of Carnitine and Acylcarnitine by Mercuric Chloride Is Reversed by 2,3-Dimercapto-1-Propanesulfonic Acid in Rats

2010 ◽  
Vol 29 (3) ◽  
pp. 313-317
Author(s):  
Waleed A. Al-Madani ◽  
Nikhat J. Siddiqi ◽  
Abdullah S. Alhomida ◽  
Haseeb A. Khan ◽  
Ibrahim A. Arif ◽  
...  
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Mercuric Chloride ◽  
Free Carnitine ◽  
Male Rats ◽  
Significant Protection ◽  
Total Carnitine ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Wistar Male Rats

This investigation was aimed to study the effect of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on mercuric chloride (HgCl2)-induced alterations in urinary excretion of various carnitine fractions including free carnitine (FC), acylcarnitine (AC), and total carnitine (TC). Different groups of Wistar male rats were treated with HgCl2 at the doses of 0.1, 0.5, 1.0, 2.0, and 3.0 mg/kg body weight, and the animals were sacrificed at 24 hours following HgCl2 injection. A separate batch of animals received HgCl2 (2 mg/kg) with or without DMPS (100 mg/kg) and sacrificed at 24 or 48 hours after dosing. Administration of HgCl2 resulted in statistically significant and dose-dependent increase in the urinary excretion of FC, AC, and TC in rats. However, the ratio of urinary AC:FC was significantly decreased by HgCl2. Pretreatment with DMPS offered statistically significant protection against HgCl2-induced alterations in various urinary carnitine fractions in rats.

scholarly journals Ethanol and glycogen synthesis in cardiothoracic and skeletal muscles following glucose re-feeding after starvation in the rat

1992 ◽  
Vol 288 (2) ◽  
pp. 445-450 ◽  
Author(s):  
D Xu ◽  
R Thambirajah ◽  
T N Palmer
Keyword(s):  
Blood Glucose ◽  
Skeletal Muscles ◽  
Glycogen Synthesis ◽  
Ethanol Administration ◽  
Ethanol Treatment ◽  
Glycaemic Response ◽  
Glucose Administration ◽  
Glycogen Deposition ◽  
Dose Dependent ◽  
Glucose Availability

The pattern of glycogen deposition in individual cardiothoracic and skeletal muscles in response to oral and intraperitoneal glucose administration was examined in 40 h-starved rats. Rates of glycogen synthesis were consistently higher in oxidative muscles than in non-oxidative muscles. Intragastric ethanol administration was associated with an impaired glycaemic response and the almost total abolition of glycogen deposition in oxidative muscles in response to oral or intraperitoneal glucose re-feeding. This effect was dose-dependent and differential, in that ethanol produced no equivalent impairment in glycogen deposition in non-oxidative muscles. Ethanol treatment also selectively promoted glycogenolysis in oxidative muscles in the starved state. There was positive correlation (P < 0.001) between the decrease in glycogen levels in soleus and diaphragm muscles in response to increasing ethanol doses and blood glucose and lactate concentrations after intraperitoneal glucose administration, implying that the basis for the impairment in glycogen synthesis may be diminished glucose availability. The mechanism whereby ethanol may differentially compromise carbohydrate metabolism in oxidative muscles is discussed.

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