Protective Effects of Selenium, N-Acetylcysteine and Vitamin E Against Acute Ethanol Intoxication in Rats.

The aim of this study was to determine possible protective influences of selenium (Se), N-acetylcysteine (NAC), and vitamin E (Vit E) against acute ethanol (EtOH) intoxication. Thirty-six rats were divided into six groups: I (control), II (EtOH), III (EtOH + Se), IV (EtOH + Vit E), V (EtOH + NAC), and VI (EtOH + mix). Except group I, EtOH was given the other pretreated (groups III, IV, V, and VI) and untreated groups (group II). Compared with the EtOH group, serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, and creatine kinase-MB levels were significantly decreased in all pretreated groups, whereas slightly diminished amylase and lipase were observed. Compared with the control group, a remarkably lower total antioxidant status (TAS), but higher total oxidant status (TOS), and oxidative stress index (OSI) were seen in brain, liver, and kidney tissues. The values of these parameters were less affected from EtOH-exposed brain tissue of EtOH + NAC and liver of EtOH + mix groups. Both significant decrease of catalase activity and marked increases of adenosine deaminase and myeloperoxidase were determined only in liver tissue of the EtOH group. Activities of these enzymes were restored in almost all pretreated groups. Moreover, an increase of xanthine oxidase activity was prevented in brain tissue of pretreated groups. In histopathological examination of the liver, hydropic degeneration, sinusoidal dilatation, mononuclear cell infiltration, and marked congestion, which were seen in the EtOH group, were prevented in all pretreated groups. Relative protection against acute EtOH toxicity, in both single and combined pretreatments of Se, NAC, and Vit E supplementation, was probably through antioxidant and free radical-neutralizing effects of foregoing materials.

Natural Products for the Prevention and Treatment of Hangover and Alcohol Use Disorder.

Alcoholic beverages such as beer, wine and spirits are widely consumed around the world. However, alcohol and its metabolite acetaldehyde are toxic and harmful to human beings. Chronic alcohol use disorder or occasional binge drinking can cause a wide range of health problems, such as hangover, liver damage and cancer. Some natural products such as traditional herbs, fruits, and vegetables might be potential dietary supplements or medicinal products for the prevention and treatment of the problems caused by excessive alcohol consumption. The aim of this review is to provide an overview of effective natural products for the prevention and treatment of hangover and alcohol use disorder, and special emphasis is paid to the possible functional component(s) and related mechanism(s) of action.

Parental binge alcohol abuse alters F1 generation hypothalamic gene expression in the absence of direct fetal alcohol exposure.

Adolescent binge alcohol exposure has long-lasting effects on the expression of hypothalamic genes that regulate the stress response, even in the absence of subsequent adult alcohol exposure. This suggests that alcohol can induce permanent gene expression changes, potentially through epigenetic modifications to specific genes. Epigenetic modifications can be transmitted to future generations therefore, and in these studies we investigated the effects of adolescent binge alcohol exposure on hypothalamic gene expression patterns in the F1 generation offspring. It has been well documented that maternal alcohol exposure during fetal development can have devastating neurological consequences. However, less is known about the consequences of maternal and/or paternal alcohol exposure outside of the gestational time frame. Here, we exposed adolescent male and female rats to a repeated binge EtOH exposure paradigm and then mated them in adulthood. Hypothalamic samples were taken from the offspring of these animals at postnatal day (PND) 7 and subjected to a genome-wide microarray analysis followed by qRT-PCR for selected genes. Importantly, the parents were not intoxicated at the time of mating and were not exposed to EtOH at any time during gestation therefore the offspring were never directly exposed to EtOH. Our results showed that the offspring of alcohol-exposed parents had significant differences compared to offspring from alcohol-naïve parents. Specifically, major differences were observed in the expression of genes that mediate neurogenesis and synaptic plasticity during neurodevelopment, genes important for directing chromatin remodeling, posttranslational modifications or transcription regulation, as well as genes involved in regulation of obesity and reproductive function. These data demonstrate that repeated binge alcohol exposure during pubertal development can potentially have detrimental effects on future offspring even in the absence of direct fetal alcohol exposure.

Biomimetic enzyme nanocomplexes and their use as antidotes and preventive measures for alcohol intoxication.

Organisms have sophisticated subcellular compartments containing enzymes that function in tandem. These confined compartments ensure effective chemical transformation and transport of molecules, and the elimination of toxic metabolic wastes. Creating functional enzyme complexes that are confined in a similar way remains challenging. Here we show that two or more enzymes with complementary functions can be assembled and encapsulated within a thin polymer shell to form enzyme nanocomplexes. These nanocomplexes exhibit improved catalytic efficiency and enhanced stability when compared with free enzymes. Furthermore, the co-localized enzymes display complementary functions, whereby toxic intermediates generated by one enzyme can be promptly eliminated by another enzyme. We show that nanocomplexes containing alcohol oxidase and catalase could reduce blood alcohol levels in intoxicated mice, offering an alternative antidote and prophylactic for alcohol intoxication.

[Simulation of parameters of alcohol-oxidizing enzyme systems and pathomorphological characteristics in situations of acute ethanol poisoning and ischemic heart disease].

Morphometric characteristics and forensic chemical information used in diagnostics of acute ethanol intoxication and coronary heart disease in conjunction with macro- and microscopic pathomorphological signs of the changes in the heart, liver, and kidneys provide data that may suggest the presence of pathology but do not permit to reliably identify it. In this context, evaluation of activities of alcohol-oxidizing enzyme systems acquires clinical significance. The analysis of correlations between quantitative parameters supplemented by the construction of binary models allows to objectively interpret the conclusions about the cause of death in each concrete case of acute ethanol poisoning and coronary heart disease.

An unusual form of fatal ethanol intoxication.

Forensic pathologists are very familiar with deaths due to ethanol intoxication. The overwhelming majority of these deaths are a result of the oral ingestion of ethanol. We report an unusual case of an individual who expired in his secured residence after self administration of a wine enema. Toxicology showed an ethanol concentration of 0.40 g/dL in the blood and 0.41 g/dL in the vitreous fluid. Scene investigation was of paramount importance in determining the unusual method by which the decedent absorbed the alcoholic beverage.

[Morphometric characteristic of some structures of the human brain in normal conditions and in acute ethanol intoxication]. / Morfometricheskaia kharakteristika struktur golovnogo mozga cheloveka v norme i v usloviiakh ostroi intoksikatsii étanolom.

In order to establish the neuro-stromal interrelations in the human brain under normal conditions and after extreme influences, different parts of this organ were studied in 14 persons who died suddenly and in 20 persons who died of ethyl alcohol poisoning. A complex of histological, histochemical, planimetric and morphometric methods were used. The specific area of normal neurocytes was shown to be the largest in the medulla oblongata, while that one of the fibers--in the cerebral cortex. Vascularization of the latter is minimal, being much higher in the medulla oblongata. In alcohol intoxication, the area, occupied by neurocytes, was decreased in the cerebral cortex, thalamus and cerebellum due to the destruction of some portion of these cells. In the medulla oblongata neurocytes appear to be more resistant to ethanol. The capillary diameter in the brain areas studied decreased because of the drop in the tone of cerebral arteries, but the number of these vessels per standard area of section was increased as a result of compensatory opening of reserve capillaries.

[Histochemical changes in the hypothalamus, hypophysis, and adrenal glands observed in ethanol poisoning]. / Gistokhimicheskie izmeneniia v gipotalamuse, gipofize i nadpochechnikakh pri otravlenii étilovym spirtom.

A comprehensive morphological-and-histochemical study of neuroendocrinal internals in cases of ethanol poisonings was undertaken. Actual forensic medical materials were used (62 cadavers) to make morphometry examinations of the hypothesis and adrenal glands. Besides, the distribution of alcohol dehydrogenase and acetaldehyde dehydrogenase was investigated in the mediatory differential brain sections, i.e. cerebellum, locus coeruleus, dorsal raphe nucleus, hypothalamus and adrenal glands. A differential distribution of ethanol-oxidizing enzymes as well as their changes in ethanol lethal poisoning were established; additionally, a variety of morphological signs were defined, which enable the differential diagnosis of a death reason in acute alcoholic intoxication.

Preservation of intestinal structural integrity by zinc is independent of metallothionein in alcohol-intoxicated mice.

Intestinal-derived endotoxins are importantly involved in alcohol-induced liver injury. Disruption of intestinal barrier function and endotoxemia are common features associated with liver inflammation and injury due to acute ethanol exposure. Zinc has been shown to inhibit acute alcohol-induced liver injury. This study was designed to determine the inhibitory effect of zinc on alcohol-induced endotoxemia and whether the inhibition is mediated by metallothionein (MT) or is independent of MT. MT knockout (MT-KO) mice were administered three oral doses of zinc sulfate (2.5 mg zinc ion/kg body weight) every 12 hours before being administered a single dose of ethanol (6 g/kg body weight) by gavage. Ethanol administration caused liver injury as determined by increased serum transaminases, parenchymal fat accumulation, necrotic foci, and an elevation of tumor necrosis factor (TNF-alpha). Increased plasma endotoxin levels were detected in ethanol-treated animals whose small intestinal structural integrity was compromised as determined by microscopic examination. Zinc supplementation significantly inhibited acute ethanol-induced liver injury and suppressed hepatic TNF-alpha production in association with decreased circulating endotoxin levels and a significant protection of small intestine structure. As expected, MT levels remained undetectable in the MT-KO mice under the zinc treatment. These results thus demonstrate that zinc preservation of intestinal structural integrity is associated with suppression of endotoxemia and liver injury induced by acute exposure to ethanol and the zinc protection is independent of MT.

Brain neuronal degeneration caused by episodic alcohol intoxication in rats: effects of nimodipine, 6,7-dinitro-quinoxaline-2,3-dione, and MK-801.

Rats repeatedly intoxicated with alcohol (ethanol, three times daily) over a 4-day period display neuronal degeneration in the dentate gyrus; entorhinal, piriform, insular, orbital, and perirhinal cortices; and in the olfactory nerve fibers and terminals in the olfactory bulb. Postulating a role for excitotoxicity, we have attempted to prevent the degeneration using antagonists that are neuroprotective in this type of brain damage. In an initial study, continuous subcutaneous infusion of a high dose of the glutamate/NMDA receptor antagonist MK-801 (2 mg/kg/day) by itself caused extensive neuronal degeneration in several brain regions and severe behavioral intoxication that precluded survival if combined with high blood alcohol levels (approximately 300 mg/dl). Moreover, the lower, nonneurotoxic blood alcohol levels (approximately 150 mg/dl) that were compatible with survival worsened the MK-801-induced brain damage. In a subsequent experiment, daily intraperitoneal injections of a lower dose of MK-801 (1 mg/kg/day) resulted in no MK-801 toxicity and, when combined with neurotoxic levels of alcohol, no reduction in alcohol-induced neurotoxicity. Nimodipine, a voltage-gated Ca2+ channel blocker, reduced the neuronal damage in the dentate gyrus, but greatly increased it in the piriform cortex when administered intragastrically at 600 mg/kg/day; it provided no protection from alcohol-dependent degeneration when given intragastrically at 100 mg/kg/day. Continuous intracerebroventricular delivery of 0.24 to 0.29 mg/day of 6,7-dinitro-quinoxaline-2,3-dione, a glutamate/alpha-amino-3-hydroxy-5-methyl-4-isoxazole receptor antagonist, failed to diminish alcohol-dependent neuronal damage in any brain region. We conclude that brain damage from episodic "binge" alcohol intoxication is not primarily mediated by excitotoxic mechanisms, implying that other, nonexcitotoxic pathophysiological mechanisms, are involved. Furthermore, MK-801, far from protecting from the alcohol-induced damage, at high doses causes widespread neuropathology that is significantly potentiated by alcohol.

[The effect of the preliminary intake of mineral waters in acute alcoholic intoxication (an experimental study)]. / Vliianie predvaritel'nogo priema mineral'nykh vod pri ostroi alkogol'noi intoksikatsii (éksperimental'noe issledovanie).

101 male Wistar rats (body mass 180-200 g) received a single dose of ethanol in two concentrations--96% and 30%. High ethanol concentrations produced a direct damage to gastric and duodenal mucosa. 30% ethanol inhibited secretion of glucagon, insulin and aldosterone. This inhibition rapidly changes for the hormones rise in the blood. Hydrocortisone was high over the experiment. Previous intake of mineral water prevents damage to the gastroduodenal mucosa induced by 96% ethanol and modifies the hormonal response provoked by 30% ethanol as evident from reduced expression of the two phases.

[Morphofunctional changes of the neurosecretory system and microcirculatory bed of the hypothalamus in patients with chronic alcoholic intoxication of varying degree]. / Morfofunktsional'nye izmeneniia neirosekretornoi sistemy i mikrotsirkuliatornogo rusla gipotalamusa u lits s khronicheskoi alkogol'noi intoksikatsiei raznoi stepeni.

Microcirculation was studied in the hypothalamus in acute alcohol intoxication. Blood flow was sharply decelerated with capillaries paretically dilated, overfilled with blood. Stasis, sludge formation and venue microthrombosis were directly related to the alcohol concentration in blood and urine. In neurosecretion areas the hemorrhagic sites were detected with neurosecretory cells activity sharply reduced. Chronical alcohol administration increased the number of functionally inactivated capillaries. These with luminal vesiculation were also found as were lymphoid cell infiltrates in venule walls. The number of capillaries inactivated in the neurosecretory system paralleled the number of dark cells that reflected the inhibition effects.

[Toxicological characteristics of teturam in an alcoholic intoxication model in rats]. / Toksikologicheskaia kharakteristika teturama na modeli alkogol'noi intoksikatsii u krys.

Study of toxicological characteristic of teturam (200 mg/kg, administered into the stomach through a tube daily for 2 weeks) on the model of alcoholic intoxication in rats (ethanol, 8 g/kg, administered into the stomach through a tube daily for 1 month) confirmed the literature data on the drug's ability to enhance or maintain ethanol-induced pathological changes in the blood and internal organs.