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

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.

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Benita L. McVicker ◽  
Karuna Rasineni ◽  
Dean J. Tuma ◽  
Mark A. McNiven ◽  
Carol A. Casey

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.


1999 ◽  
Vol 81 (04) ◽  
pp. 594-560 ◽  
Author(s):  
Florence Ganné ◽  
Marc Vasse ◽  
Jean-Louis Beaudeu ◽  
Jacqueline Peynet ◽  
Arnaud François ◽  
...  

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.


1974 ◽  
Vol 75 (3) ◽  
pp. 428-434 ◽  
Author(s):  
P.-J. Czygan ◽  
M. Breckwoldt ◽  
F. Lehmann ◽  
R. Langefeld ◽  
G. Bettendorf

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.


2020 ◽  
Vol 16 ◽  
Author(s):  
Lalitha Vivekanandan ◽  
Roxanne Gekonge Mandere ◽  
Sivakumar Thangavel

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.


Toxics ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 9
Author(s):  
Kimberly T. To ◽  
Lindsey St. Mary ◽  
Allyson H. Wooley ◽  
Mitchell S. Wilbanks ◽  
Anthony J. Bednar ◽  
...  

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.


2012 ◽  
Vol 38 (3) ◽  
pp. 83-89 ◽  
Author(s):  
Marja Ilona Kinnunen ◽  
Johanna Suihko ◽  
Nelli Hankonen ◽  
Pilvikki Absetz ◽  
Piia Jallinoja

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 ◽  
...  

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.


2000 ◽  
Vol 279 (3) ◽  
pp. R1025-R1034 ◽  
Author(s):  
Yuwaraj K. Narnaware ◽  
Pierre P. Peyon ◽  
Xinwei Lin ◽  
Richard E. Peter

In mammals, neuropeptide Y (NPY) is a potent orexigenic factor. In the present study, third brain ventricle (intracerebroventricular) injection of goldfish NPY (gNPY) caused a dose-dependent increase in food intake in goldfish, and intracerebroventricular administration of NPY Y1-receptor antagonist BIBP-3226 decreased food intake; the actions of gNPY were blocked by simultaneous injection of BIBP-3226. Goldfish maintained on a daily scheduled feeding regimen display an increase in NPY mRNA levels in the telencephalon-preoptic area and hypothalamus shortly before feeding; however, a decrease occured in optic tectum-thalamus. In both fed and unfed fish, brain NPY mRNA levels decreased after scheduled feeding. Restriction in daily food ration intake for 1 wk or food deprivation for 72 h resulted in increased brain NPY mRNA levels. Results from these studies demonstrate that NPY is a physiological brain signal involved in feeding behavior in goldfish, mediating its effects, at least in part, through Y1-like receptors in the brain.


INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (04) ◽  
pp. 34-38
Author(s):  
P Bommannavar ◽  
◽  
K. Patil

The present study was undertaken to establish the diuretic activity of alcoholic and aqueous extract of dried rhizomes of Curcuma amada Roxb in rats. Alcoholic and aqueous extracts of rhizomes were administered to experimental male Wistar rats orally at doses of 250 and 500 mg/kg and compared with furosemide (10 mg/kg) as the reference standard. The parameters measured for diuretic activity were total urine volume, urine electrolyte concentration such as sodium, potassium and chloride have been evaluated. The rats treated with alcoholic and aqueous extract of Curcuma amada in a dose of 250 and 500 mg/kg showed higher urine output when compared to the respective control. Both alcoholic and aqueous extracts have showed a significant dose-dependent increase in the excretion of electrolytes when compared to the control group. The result indicates that alcoholic and aqueous extract is an effective natriuretic and kaliuretic diuretic, which supports the traditional claim about the Curcuma amada Roxb being used as diuretics.


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