Protective effect of Flos puerariae extract following acute alcohol intoxication in mice.

BACKGROUND: The effect of Flos Puerariae extract (FPE) on alcohol metabolism, hepatic injury, and memory impairment was assessed following acute ethanol (EtOH) intoxication in mice. METHODS: The model of acute EtOH intoxication was established by intragastric administration with 8 g/kg EtOH in mice. FPE was orally administrated (gavage) once a day for 7 consecutive days. Mice were randomly divided into 4 groups: control group, model group, and FPE groups (100, 200 mg/kg). Alcohol tolerance and intoxication time, blood alcohol concentration, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in liver, aspartate amino transferase (AST) and alanine amino transferase (ALT) in serum, superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase and the formation of malondialdehyde (MDA) in both liver and brain, as well as memory ability were determined after acute alcohol exposure. RESULTS: Compared with model group, pretreatment with FPE significantly prolonged alcohol tolerance time and shortened intoxication time, which is accompanied by decreased blood alcohol concentration and elevated activities of ADH and ALDH in liver. Moreover, the index of hepatic injury, ALT, and AST activities in serum was markedly decreased by pretreatment with FPE. Additionally, decreased MDA level, enhanced GSH-px and catalase activities in liver, as well as enhanced SOD and catalase activities in brain were found in FPE pretreated mice after acute exposure to EtOH. Furthermore, FPE pretreated mice showed markedly relieved memory disruption following acute EtOH intoxication. CONCLUSIONS: This study suggests that FPE pretreatment could enhance alcohol metabolism, prevent hepatic injury, and relieve memory impairment after acute alcohol intoxication and that this effect is likely related to its modulation on the alcohol metabolizing and antioxidant enzymes.

[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.

Effects of a preparation of combined glutathione-enriched yeast and rice embryo/soybean extracts on ethanol hangover.

The effects of a preparation of combined glutathione-enriched yeast (GEY) and rice embryo/soybean (RES) extracts (20:1), GEY/RES, on experimentally induced ethanol hangover were investigated in male Sprague-Dawley rats. To evaluate the preventive effects on hangover, rats were orally administered GEY/RES (50/2.5, 100/5, or 200/10 mg/kg) for 2 weeks. At 30 minutes after the final treatment, they were challenged with 3 mL/kg ethanol (15 mL of 20% in water/kg). The blood concentrations of alcohol and acetaldehyde were analyzed up to 7 hours postchallenge. Hepatic mRNA expression levels of alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH), cytochrome P450 type 2E1 (CYP2E1), and aldehyde dehydrogenase (ALDH), were determined by real-time polymerase chain reaction. Additional rats were challenged with ethanol and, 60 minutes later, administered GEY/RES to evaluate alcohol clearance. Pretreatment with GEY/RES for 2 weeks reduced the blood concentrations of alcohol and acetaldehyde in a dose-dependent manner, lowering by 29.5% and 54.6% at the highest dose (200/10 mg/kg), respectively. The expressions of mRNAs for ADH and ALDH, the major alcohol-metabolizing enzymes, were markedly increased in the livers of rats administered GEY/RES for 2 weeks, whereas CYP2E1 mRNA was suppressed. Postchallenge treatment with GEY/RES enhanced the alcohol clearance rate by lowering blood concentrations of alcohol and acetaldehyde by 24% and 26.6%, respectively, for the highest dose group. GEY/RES remarkably eliminated 2,2-diphenyl-1-picrylhydrazyl hydrate radical and FeCl(3)-mediated lipid peroxidation in vitro and attenuated hepatic lipid accumulation following ethanol administration in vivo. Therefore, it is suggested that GEY/RES reduces the blood concentrations of alcohol and acetaldehyde not only by modulating alcohol-metabolizing enzymes, but also by exerting its antioxidant activity, and that GEY/RES could be a promising candidate for improvements of alcoholic hangover.

[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.

Effects of Puerariae radix on cell proliferation and nitric oxide synthase expression in dentate gyrus of alcohol-intoxicated Sprague-Dawley rats.

Traditionally, Puerariae radix had been used for the treatment of alcohol-related problems. In this study, effects of Puerariae radix on cell proliferation and nitric oxide synthase expression in the dentate gyrus of alcohol-intoxicated Sprague-Dawley rats were investigated via 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Alcohol administration was shown to inhibit the numbers of both BrdU-positive and NADPH-d-positive cells, while Puerariae radix treatment was shown to increase those numbers. It is possible that nitric oxide, which might play an important role in the regulation of cell proliferation, is a major target of the toxic effects of alcohol.

[The protective effect of pantothenic acid derivatives and changes in the system of acetyl CoA metabolism in acute ethanol poisoning]. / Zashchitnyi éffekt proizvodnykh pantotenovoi kisloty i izmeneniia sistemy metabolizma atsetil-KoA pri ostroi intoksikatsii étanolom.

Calcium pantothenate (CaP), calcium 4'-phosphopantothenate (CaPP), pantethine, panthenol, sulfopantetheine and CoA decrease acute toxicity of acetaldehyde in mice. All studied compounds diminish duration of the narcotic action of ethanol--ET (3.5 g/kg intraperitoneally) in mice and rats. In the latter this effect is realized at the expense of "long sleeping" and "middle sleeping" animals. CaP (150 mg/kg subcutaneously) and CaPP (100 mg/kg subcutaneously) prevent hypothermia and a decrease of oxygen consumption in rats induced by ET administration. Combined administration of ET, CaP and CaPP leads to a characteristic increase of acid-soluble CoA fractions in the rat liver and a relative decrease of acetyl CoA synthetase and N-acetyltransferase reactions. The antitoxic effect of preparations of pantothenic acid is not mediated by CoA-dependent reactions of detoxication, but most probably is due to intensification of ET oxidation and perhaps to its elimination from the organism.

Ascorbic acid and elevated SGOT levels after an acute dose of ethanol in the guinea pig.

Male guinea pigs were maintained on a vitamin C-deficient chow diet and supplemented with either 0.05 or 2.0 mg of ascorbic acid/ml drinking water for 3 weeks prior to receiving an intraperitoneal injection of 4.0 g of ethanol/kg body weight. The following biochemical parameters were measured prior to, and hourly for 12 hours after, ethanol administration: serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvate transaminase (SGPT), serum triglycerides, and blood ethanol clearance. The animals were killed 12 hours after ethanol administration and liver weight to body weight ratios and hepatic ascorbic acid concentrations determined. Acute ethanol administration resulted in a 12-fold increase in SGOT levels in animals with hepatic ascorbic acid concentrations at or below 16 mg/100 g of liver. A marked reduction, 60%, in this increase was observed in animals that had concentrations of hepatic ascorbic acid above 16 mg/100 g of liver. No effect of hepatic ascorbic acid concentration was observed on elevated levels of SGPT, serum triglycerides, or blood ethanol clearance.

Increases in liver microsomal phosphatidylethanolamine methyltransferase activity(s) in mice after short-term ethanol treatments.

Adult C57/BL mice subjected to short term ethanol liquid diets exhibited significant increases in liver microsomal phosphatidylethanolamine methyltransferase activity(s) as well as changes in microsomal lipid composition. Specifically, increases in [3H]-methyl incorporation into phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N-dimethylethanolamine were observed suggesting increases in phospholipid methyltransferase I and the first methyl transfer reaction of phospholipid methyltransferase II. Labeling of phosphatidylcholine was not affected, however. Dietary supplementation with 2% choline reduced liver methyltransferase activities of both control and ethanol treated mice. The ethanol induced increase in methyltransferase activity returned to control values upon removal of ethanol from the diet for 24 hours. It is suggested that the increase in phospholipid methyltransferase activity after chronic ethanol treatment may be responsible, in part, for alterations in the activities of certain microsomal enzymes known to be influenced by ethanol.

[Effect of acute and chronic ethanol consumption on rat brain and liver monoamine oxidase activity]. / Vliianie ostrogo i khronicheskogo potrebleniia étanola na aktivnost' monoaminoksidazy mozga i pecheni krys.

Monoamine oxidase (MAO) activity was studied in hyporthalamus, midbrain, brain stem and liver tissue of rats after single and repeated administration of ethanol using noradrenaline and dopamine as MAO substrates. Small, but statistically significant decrease in the activity MAO of the "A" type was found in rat liver tissue after repeated administration of alcohol. Both single and repeated administrations of ethanol did not affect the enzymatic activity in the brain. Prolonged administration of the MAO inhibitor parnate simultaneously with alcoholization of rats led to inhibition of the MAO activity to the same degree as in control animals treated with the parnate only.