Days Of Ethanol Administration Research Articles

Cashew nut-supplemented diet on testicular injury in rats exposed to sub-acute alcohol

Binge drinking is a major global health issue, causing over 3.3 million mortalities yearly and might induce male infertility. Cashew nut contains many constituents with health benefits. This study investigated the effect of a cashew nut-supplemented diet (CND) against ethanol-invoked testicular injury in male Wistar rats. Thirty male rats were randomly assigned to five groups (n = 6). The groups are as follows: Group 1: (fed with standard diet only), Group 2: ethanol (received 30% v/v; 4 mL /kg body weight, orally) and regular diet, Group 3: (received ethanol and fed with 5% CND), Group 4: (received ethanol and provided with CND 10%), and Group 5: (10% CND) only. After fourteen days of ethanol administration and diet regimen, animals were fasted overnight and euthanized. Testis and blood were collected for biochemical and histological analyses. Testis was investigated for oxidative stress indices, glycogen level, antioxidant biomarkers, alcohol metabolism enzymes, and histopathology. Serum cholesterol, testosterone, and follicle-stimulating hormone (FSH) levels were also determined. Ethanol caused significant inhibition/reduction of antioxidant enzymes, cholesterol, testosterone, and FSH levels. Furthermore, there were increased levels of oxidative stress markers and histological impairment of the testis. However, the treatment with CND dose-dependently decreased the oxidative stress and aberrant histological features while augmenting the lowered antioxidant systems, normalizing the alcohol metabolizing enzymes and the hormones levels. This study shows that CND might protect against testicular injury by attenuating oxidative stress and boosting antioxidant and steroidogenesis in male rats.

Rutin co-treatment prevented cognitive impairment/depression-like behavior and decreased IDO activation following 35 days of ethanol administration in male Wistar rats.

Alcohol (ethanol) is among the most popularly consumed beverages globally. Ethanol was earlier demonstrated to elicit cognitive impairment and depressive-like effects in both human and animal studies. Rutin (R) is known for its antioxidant, anti-inflammatory, immunomodulatory, and anti-depressive properties, among others. Herein, we investigate the impact of rutin on ethanol-induced cognitive impairment and depressive-like effects in rats and the involvement of the indoleaminergic pathway. Three groups of eight rats each were orally exposed to drinking water (group 1), ethanol (5g/kg body weight)-group 2 (via oral gavage), and ethanol+R (5g/kg body weight+50mg/kg body weight)-group 3 (via oral gavage) for 35 days. Results showed that exposure to ethanol significantly (p<0.0001) reduced spontaneous alternation in the Y-maze and increased immobility time in the tail suspension test (TST), which indicates cognitive impairment and depressive-like behavior in rats. We observed increased IDO activity/expression, and inflammatory responses, with attendant disruption in antioxidant systems and concomitant elevation in malondialdehyde (MDA) levels in the cerebral cortex and hippocampus. Following rutin co-exposure, an ethanol-mediated increase in indoleamine 2,3-dioxygenase [IDO] activity/expression and decrease in antioxidant enzymes, in addition to an increase in markers of inflammatory response and MDA production, was significantly (p<0.0001) prevented compared with controls. Additionally, altered behavioral indices were prevented by rutin co-exposure. Taken together, these findings reveal the involvement of the indoleaminergic pathway in rutin preventive influence against ethanol-induced cognitive impairment and depressive-like behavior in rats.

Protective effect of ethanolic extract of Actinoscirpus grossus tubers against ethanol induced liver toxicity in albino rats

Liver detoxifies majority of chemicals and plays an important role in the maintenance of homeostasis of the body. In the recent years due to overwhelming use of drugs and alcohol there is an increased incidence of liver toxicities. The tubers of Actinoscirpus grossus are used in liver disease as a liver tonic in folklore medicine; However, there is no experimental basis for its therapeutic use. Hence the present study was conducted to evaluate the hepatoprotective potentials of ethanolic extract of Actinoscirpus grossus tubers in ethanol induced hepatotoxicity in albino rats. Daily administration of 20% ethanol v/v p.o. at a dose of 5 g/kg for 30 consecutive days caused significant liver toxicity and there after maintained for 15 consecutive days with normal rat pellet and water ad libitum. The treatment groups were administered with group specific drugs for 15 consecutive days after 30 days of ethanol administration and control group rats were maintained for 15 consecutive days with normal rat pellet and water ad libitum. Liver toxicity was assessed on 45th day by estimating biochemical, histological and antioxidant level. Daily administration of 20% ethanol significantly increased liver enzymes and caused oxidative stress by increase in the lipid peroxidation and reduction in the catalase and glutathione peroxidase activity in liver homogenate. The histopathological examination revealed micro vesicular and macro vesicular fatty changes predominantly with mild periportal inflammation, cell infiltrate and areas of mild dilatation of sinusoids with ballooning degeneration of hepatocytes. Treatment with ethanolic extract of A. grossus tuber significantly restored the liver enzymes especially SGOT and attenuated elevated lipid peroxidation and restored catalase and glutathione peroxidase activity. The histopathological changes revealed significant reduction in the hepatocyte ballooning portal fibrosis. Thus, tubers of A. grossus plant may serve as reservoir of natural products having diverse functions and could be utilised as a potent hepatoprotective agent.

Seven-day ethanol administration influence on the rat brain histaminergic neurons

The purpose of the study is to clarify the effect of 7 days of ethanol administration upon brain histaminergic neurons in rats. Male Wistar rats were injected intraperitoneally (i.p.) with 20% ethanol/saline (0.85% NaCl) daily, over 7 days, whereas control rats were given saline. The animals were decapitated 24 h after the 7th injection and samples of hypothalamus were prepared for light and electron microscopy, accompanied by morphometry to examine the histaminergic neurons. It was found that ethanol administration gradually decreased the duration of alcohol-induced sleep and decreased the total amount of histaminergic neurons and the amount of histologically normal neurons, but increased the amount of hypochromic neurons and shadow cells. The histaminergic neuron bodies and nuclei decreased in size. The ultrastructural changes in histaminergic neurons demonstrated activation of their nuclear apparatus, both destruction or hypertrophy and hyperplasia of organelles, especially lysosomes. The histochemical examination revealed the activation of lactate dehydrogenase and acid phosphatase, and inhibition of NADH−, NADPhH, and succinate dehydrogenases. Following 7 days of ethanol administration, histaminergic neurons exhibit the structural signs of hyperactivity, which can be related to neuronal adaptation to the actions of ethanol, and increased behavioral tolerance to ethanol.

Механізми виникнення переддіабетичного стану за умов розвитку хронічної алкогольної інтоксикації

We investigated the changes in key parameters of carbohydrate and lipid metabolism, which correspond to the clinical picture that accompanies the development of prediabetic condition on the background of chronic alcohol intoxication. From the analysis of glycemic curves obtained during the insulin-glucose test, a speed of glucose uptake by peripheral tissues increased at the 1st day (1.5 fold) and the third day (1.3 fold) of administration of alcohol solution. At the later periods, at 7 and 11 days of ethanol administration, a decreased rate of glucose uptake in animals with chronic alcohol intoxication was detected. We also detected an increased content of serotonin in the blood serum and a decreased (1.2 fold) serotonin content in rat brain during the whole period of development of chronic alcohol intoxication.

Ethanol-induced neurotoxicity is counterbalanced by increased cell proliferation in mouse dentate gyrus

Chronic ethanol abuse leads to degenerative changes in the hippocampus, which may result in subsequent cognitive impairment. Since the hippocampus retains the ability to produce neurons through adulthood, in the present study we examined if ethanol-induced neuronal loss could be counterbalanced by cell proliferation in mouse dentate gyrus (DG). A total of 14 days of ethanol administration resulted in marked increase in cells positive for TdT-mediated dUTP nick-end labeling in all hippocampal regions studied, indicating that neurons die throughout the hippocampus by apoptotic mechanism. However, cresyl violet staining revealed approximately 20% neuronal loss following ethanol administration in CA1 and CA2 fields ( P<0.01 and P<0.05, respectively), but not in DG. At the same time ethanol caused 2-fold increase in the number of proliferating cells in subgranular zone of DG. Thus, long-term ethanol intoxication causes permanent damage to CA1 and CA2, but not to DG which can be counterbalanced by ongoing neurogenesis.

HSP70 Induction in the Brain Following Ethanol Administration in the Rat: Regulation by Glutathione Redox State

Changes in glutathione (GSH) and glutathione disulfide (GSSG) levels and/or redox status have been suggested to mediate the induction of heat shock proteins (HSPs) that follows exposure to oxidizing agents such as ethanol. Here we report the effects of ethanol administration to rats at intracellular levels of GSH, GSSG, HSP70, and protein carbonyls in brain and liver. Following 7 days of ethanol administration, there was a significant decrease in GSH, a significant induction of HSP70, and a significant increase in protein carbonyls in all brain regions studied and in liver. In cortex, striatum, and hippocampus there was a significant correlation between (a) the decrease in GSH, (b) the increase in GSSG, and (c) the decrease in GSH/GSSG ratio and HSP70 levels induced in response to ethanol. These data support the hypothesis that a redox mechanism may be involved in the heat-shock signal pathway responsible for HSP70 induction in the brain.

TIME COURSE AND GENETIC VARIATION IN THE REGULATION OF CALCIUM CHANNEL ANTAGONIST BINDING SITES IN RODENT TISSUES DURING THE INDUCTION OF ETHANOL PHYSICAL DEPENDENCE AND WITHDRAWAL

Physical dependence was induced by ethanol inhalation in male Sprague-Dawley rats and, in parallel experiments, in two lines of mice (WSR and WSP) genetically selected for differential severity of ethanol withdrawal. In dependent rats [3H]nitrendipine binding sites were significantly increased in cerebral cortex, cardiac and smooth muscle (vas deferens). Cerebral cortical membranes were the first to show an increase, the Bmax for nitrendipine binding rising sharply after 3-4 days of ethanol administration, whereas binding sites in the other tissues increased after 5-6 days. Nitrendipine binding affinity in all tissues was consistently reduced immediately preceding the rise in Bmax to a new steady state, but then returned to control values. Between 6 and 10 days of ethanol exposure there was no further increase in the Bmax for nitrendipine binding, and on removal of ethanol, the numbers of nitrendipine binding sites fell precipitously to control levels within 24 h of withdrawal. In the genetically selected mice, the up-regulation of nitrendipine binding sites in cardiac membranes was significantly greater in the WSP line. This correlates with severity of physical signs of withdrawal and parallels previous results obtained in brain. The results are consistent with an increase in the synthesis and membrane insertion of dihydropyridine sensitive calcium channel proteins in several tissues during the induction of ethanol dependence and suggest that in the brain this change may play a role in the ethanol withdrawal syndrome.

Ethanol inhibits nonadrenergic, noncholinergic neurotransmission in the anococcygeus muscle of the rat.

The anococcygeus muscle of the rat is innervated by both excitatory adrenergic and inhibitory nonadrenergic, noncholinergic (NANC) neurons. The transmitter released from NANC neurons appears to be nitric oxide or a related molecule. In vitro, acute administration of ethanol inhibited, in a dose-dependent manner, NANC-induced relaxation of anococcygeus muscle obtained from ethanol-naive animals. Two days of in vivo ethanol administration resulted in an increase in the maximal relaxation induced by stimulation of NANC neurons and in a significant shift to the right of the acute ethanol dose-response curve for inhibition of NANC relaxation. The sensitivity of the anococcygeus muscle to relaxation induced by the nitric oxide donors, acidified sodium nitrite or sodium nitroprusside, was not altered significantly by acute in vitro or chronic ethanol treatment 2 days in vivo. These data suggest that acutely administered in vitro ethanol inhibits the production of nitric oxide induced by stimulation of NANC neurons. Data further suggest that 2 days of ethanol administration in vivo produce an enhanced responsiveness of the NANC neurons to transmural stimulation and that this enhanced responsiveness accounts for the tolerance to the inhibition induced by the acutely administered ethanol in vitro.

The effect of chronic ethanol on glutamate binding in human and rat brain

Quantitative autoradiographic techniques demonstrate that chronic alcohol administration causes a decrease in [ 3H]-glutamate binding to hippocampal N-methyl-D-aspartate (NMDA) receptors. A 14% decrease in [ 3H]-glutamate binding in the hippocampal CA 1 region is seen both in the rat after five days of ethanol administration and in postmortem hippocampal tissues from alcoholics. In the rat, 24 hr ethanol withdrawal values are intermediate between control and alcohol binding levels. There was no significant effect of ethanol on [ 3H]-glutamate binding in the cortex or caudate.

Effects of long-term ethanol inhalation on the immune and hematopoietic systems of the rat.

An inhalation method of ethanol administration was used to study the effects of 14 days of ethanol administration on the immune and hematopoietic systems of the rat. A decrease in cellularity was found in the spleen, thymus, and bone marrow of ethanol-treated rats. Although the red blood cell count, white blood cell count, and hemoglobin concentration were not significantly different between treatment and control groups, treatment with ethanol altered the relative proportion of lymphocytes and polymorphonuclear leukocytes in the peripheral blood. The granulocyte-macrophage progenitor cells in the bone marrow were unaffected by ethanol treatment, but a significant decline in the number of erythroid progenitor cells was noted in ethanol-treated rats. Splenic lymphocytes, although fewer in number in the ethanol-treated rats, showed no significant difference in ability to proliferate when stimulated by nonspecific mitogens.

Ethanol reduces hepatic estrogen-2-hydroxylase activity in the male rat

Brief exposure to intoxicating levels of ethanol in the male rat produced a marked reduction in a major hepatic enzyme responsible for estrogen metabolism (estrogen-2-hydroxylase). After 4 days of ethanol administration the specific activity of this enzyme decreased by 70% and remained decreased for 6 days following alcohol withdrawal. Enzyme activity returned to control levels by two weeks. However, if animals were retreated with ethanol for one day each week the enzyme activity remained low. Kinetic analysis of the enzymatic activity from ethanol-treated rats showed a decrease in specific activity (Vmax) with no alteration in substrate affinity (apparent Km). The decrease in enzyme activity persisted long after ethanol disappeared from the blood and concentrations of ethanol from 20–100 mM had no effect on enzyme activity when added in vitro . A similar effect of ethanol on hepatic estrogen metabolism in humans may partially explain the elevated serum estrogen levels and the signs of hyperestrogenization observed in male alcoholic patients.

Genetic and environmental factors affecting ethanol metabolism in man.

The relative contribution of genetic and environmental factors to maintaining twofold differences in rates of ethanol elimination from plasma was examined in 14 sets of nonmedicated, nonhospitalized healthy twins. After a single oral dose of 1 ml. per kilogram of 95 per cent ethanol, intrapair differences in rates of elimination were less in identical than in fraternal twins. Thew results indicate that individual differences in rates of ethanol elimination among the 28 twins were genetically controlled and that environmental factors played a negligible role. In 6 prisoners in solitary confinement, rates of ethanol metabolism increased in 3 but declined in the remaining 3 after 21 days of ethanol administration. Rates of antipyrine elimination from plasma were accelerated by ethanol administration in each of the 6 volunteers. Considerable individual variation occurred in the degree to which ethanol shortened plasma antipyrine half‐lifes; reduction ranged from 4 to 37 per cent of the initial antipyrine half‐life. These results suggest that ethanol administration for 21 days at this dosage fails to alter consistently the rate of its own metabolism but increases antipyrine metabolism in all subjects to varying extents.