Sukhes Mukherjee

Consequences of Alcohol Consumption on Neurotransmitters -An Overview

Alcohol one of the important products of the global addiction alters brain function by interacting with multiple neurotransmitter systems, thereby disrupting the delicate balance between inhibitory and excitatory neurotransmitters. Alcohol positively reinforces drinking by producing a mild euphoria. The reinforcing effects of alcohol are mediated by several neurochemical systems and are associated with some of the behavioral manifestations of intoxication. Alcohol consumption is initially accompanied by decreased attention, alterations in memory, mood changes and drowsiness. Generally all vital functions of brain depend on a delicate balance between excitatory and inhibitory neurotransmission,which in turn dependent on short and long term alcohol consumption. Detailed understanding of alcohols mechanism of action on the neurotransmitters of brain is a prerequisite in discovering effective treatments for both alcohol abuse and alcoholism. This review covers the elaborate literature on the subject and highlights the functions and interactions of neurotransmitters and alcoholism.

Oxidative stress is the primary event: Effects of ethanol consumption in brain.

Damaging effects of reactive oxygen species on living systems are well documented. They include oxidative attack on vital cell constituents. Chronic ethanol administration is able to induce an oxidative stress in the central nervous system. In the present study, 16–18 week-old male albino rats of Wistar strain were exposed to different concentration of ethanol for 4 weeks. This exposure showed profound effect on body weight. Ascorbic acid level; and activities of alkaline phosphatase and aspartate transaminase in the brain are dependent on the concentration of ethanol exposure. Chronic ethanol ingestion elicits statistically significant increase in thiobarbituric acid reactive substances level and decrease in gluatathione level in the brain. It reduces superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities in a dose dependent manner. However, histological examination could not reveal any pathophysiological changes. Therefore, we conclude that biochemical alterations and oxidative stress related parameters respond early in alcoholism than the histopathological changes in brain.

Alcoholism and its effects on the central nervous system

Alcohol abuse is a major health problem worldwide, resulting to extensive admissions in many general hospitals. The overall economic cost of alcohol abuse is enormous worldwide. As a small molecule, alcohol can easily cross membrane barriers and reach different parts of the body very quickly. Attainment of its equilibrium concentration in different cellular compartments depends on the respective water content. Alcohol can affect several parts of the brain, but, in general, contracts brain tissues, destroys brain cells, as well as depresses the central nervous system. Excessive drinking over a prolonged period of time can cause serious problems with cognition and memory. Alcohol interacts with the brain receptors, interfering with the communication between nerve cells, and suppressing excitatory nerve pathway activity. Neuro-cognitive deficits, neuronal injury, and neurodegeneration are well documented in alcoholics, yet the underlying mechanisms remain elusive. The effect can be both direct and/ or indirect. In this review we highlighted the role of alcoholism on the CNS and its impact on human health.

Biochemical and immunological basis of silymarin effect, a milk thistle (Silybum marianum) against ethanol-induced oxidative damage

Ethanol metabolism induces generation of excessive amount of reactive oxygen species (ROS) which results in immune dysfunction. We examined the efficacy of silymarin on ethanol-induced oxidative stress, immunomodulatory activity, and vascular function in mice blood. Effectiveness of silymarin was compared with potent antioxidant ascorbic acid. In the present study, 8- to 10-week-old male BALB/c mice (20–30 g) were divided into the four groups of six each. One group were fed with ethanol (1.6 g/kg body weight), while second group were fed with ethanol (1.6 g/kg body weight) and silybin (250 mg/kg body weight), and the third group were exposed to ethanol (250 mg/kg body weight) and ascorbic acid (250 mg/kg body weight) per day for 12 weeks. The control group was fed with isocaloric glucose solution instead of ethanol. Ethanol exposure significantly increased thiobarbituric acid reactive substance (TBARS) and nitrite levels besides glutathione-S-transferase (GST) activity, and significantly decreased reduced glutathione (GSH) content and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) in whole blood hemolyzate, while silymarin treatment significantly normalized these altered parameters. Silymarin significantly prevented ethanol-induced, elevated activities of interleukin (IL)-10, tumor necrosis factor (TNF)-α, γ interferon (IFN-γ), vascular endothelial growth factor (VEGF)-A, and transforming growth factor (TGF)-β1, as well as decreased IL-4 activity in mice blood. These results were comparable with the activity of ascorbic acid.

Effects of chronic ethanol exposure on renal function tests and oxidative stress in kidney.

After administration, ethanol and its metabolites go through the kidneys and are excreted into urine. The kidney seems to be the only vital organ generally spared in chronic alcoholics. Therefore, we investigated the multiple effects of chronic ethanol exposure on renal function tests and on oxidative stress related parameters in the kidney. Chronic ethanol (1.6 g ethanol/ kg body weight/ day) exposure did not show any significant change in relative weight (g/ 100g body weight) of kidneys, serum calcium level or glutathione s-transferase activity. However, urea and creatinine concentration in serum, and TBARS level in kidney elevated significantly, while reduced glutathione content and activities of glutathione peroxidase, glutathione reductase and superoxide dismutase diminished significantly after 12 weeks of ethanol exposure. Catalase activity showed increased activity after 4 weeks of ethanol exposure and decreased activity after 12 weeks of ethanol exposure. Genesis of renal ultrastructural abnormalities after 12 weeks of ethanol exposure may be important for the development of functional disturbances. This study revealed that chronic ethanol exposure for longer duration is associated with deleterious effects in the kidney.

Effects of chronic ethanol consumption in blood: A time dependent study on rat

Alcohol consumption and health outcomes are complex and multidimensional. Ethanol (1.6g / kg body weight/ day) exposure initially affects liver function followed by renal function of 16–18 week-old male albino rats of Wistar strain weighing 200–220 g. Chronic ethanol ingestion increased in thiobarbituric acid reactive substances level and glutathione s-transferase activity; while decreased reduced gluatathione content and activities of catalase, glutathione peroxidase and glutathione reductase in a time dependent manner in the hemolysate. Though superoxide dismutase activity increased initially might be due to adaptive response, but decreased later. Elevation of serum nitrite level and transforming growth factor-b1 activity indicated that long-term ethanol consumption may cause hepatic fibrosis and can elicit pro-angiogenic factors. However, no alteration in vascular endothelial growth factor-C activity indicated that ethanol consumption is not associated with lymphangiogenesis. Therefore, we conclude that long-term ethanol-induced toxicity is linked to an oxidative stress, which may aggravate to fibrosis and elevate pro-angiogenic factors, but not associated with lymphangiogenesis.

ROLE OF PLASMA AMINO ACIDS AND GABA IN ALCOHOLIC AND NON-ALCOHOLIC FATTY LIVER DISEASE- A PILOT STUDY

Alcohol appears to affect brain function, primarily by interfering with the action of gamma-aminobutyric acid (GABA) and other neurotransmitters. As alcohol is mainly metabolized in the liver, therefore we undertook this pilot study to monitor the patterns of changes in plasma amino-acid concentrations due to alcoholic and nonalcohol fatty liver disease and their relation with plasma GABA level. Plasma amino-acid concentrations were measured in 25 alcoholic liver disease (ALD) patients, 18 non-alcoholic fatty liver disease (NAFLD) patients, and 24 age and sex matched control subjects by HPLC. GABA concentration was elevated, while isoleucine and leucine levels reduced significantly in ALD patients compared to the control subjects. Methionine and phenylalanine levels elevated and valine content reduced significantly in ALD patients compared to other two groups, and GABA level was significantly correlated with methionine and phenylalanine. Plasma concentration of lysine was significantly reduced in both groups of liver disease patients compared to the control group, but was not correlated with GABA level. Glycine and tyrosine levels reduced significantly in NAFLD patients compared to other two groups and were significantly correlated with GABA. Interestingly, though amino acids such as alanine, histidine, proline and serine were not affected by liver diseases, but were significantly correlated with GABA level. This pilot study indicated that alcoholic liver disease presented a more deranged plasma amino acid pattern than nonalcoholic, and the amino acid imbalances. More studies are necessary to identify the role of any particular amino acid on brain function and on neurotransmitter(s).

Long term ethanol consumption leads to lung tissue oxidative stress and injury.

Background: Alcohol abuse is a systemic disorder. The deleterious health effects of alcohol consumption may result in irreversible organ damage. By contrast, there currently is little evidence for the toxicity of chronic alcohol use on lung tissue. Hence, in this study we investigated long-term effects of ethanol in the lung. Results: Though body weight of rats increased significantly with duration of exposure compared to its initial weight, there was no significant change in relative weight (g/100 g body weight) of lung due to ethanol exposure. The levels of thiobarbituric acid reactive substances (TBARS), nitrite, protein carbonyl, oxidized glutathione (GSS G), redox ratio (GSS G/ GSH ) and GST activity elevated; while reduced glutathione (GSH ) level and activities of glutathione reductase (GR), glutathione peroxidase (GPx), catalase, superoxide dismutase (SOD) and Na+K+ATPase reduced significantly with duration of ethanol exposure in the lung homogenate compared to the control group. Total matrix metalloproteinase activity elevated in the lung homogenate with time of ethanol consumption. Histopathologic examination also demonstrated that severity of lung injury enhanced with duration of ethanol exposure. Methods: 16–18 week-old male albino Wistar strain rats weighing 200–220 g were fed with ethanol (1.6 g/kg body weight/day) up to 36 weeks. At the end of the experimental period, blood samples were collected from reteroorbital plexus to determine blood alcohol concentration and the animals were sacrificed. Various oxidative stress-related biochemical parameters, total matrix metalloproteinase activity and histopathologic examinations of the lung tissues were performed. Conclusions: Results of this study indicate that long-term ethanol administration aggravates systemic and local oxidative stress, which may be associated with lung tissue injury.

Effects of long term ethanol consumption mediated oxidative stress on neovessel generation in liver

Angiogenesis, the growth of new blood vessels, is essential during tissue repair. Though most molecular mechanisms of angiogenesis are common to the liver and other organs, there was no report available whether alcoholic liver disease also causes angiogenesis. In this study, we examined the effects of long term ethanol (1.6 g/kg body weight/day) consumption on angiogenic responses in the liver of male Wistar strain albino rats (16–18 weeks old, weighing 200–220 g) up to 36 weeks. Chronic ethanol consumption was associated with not only elevated oxidative stress, and altered cytokines expression, but also developed large von Willebrand factor, fibrosis and activation of matrix metalloproteinases. Moreover, vascular endothelial growth factor-receptor 2 (VEGF-R2, fetal liver kinase 1: Flk-1/KDR) expression and neovessel generation in the rat liver were noted after 36 weeks of ethanol consumption. Thus our study provides novel evidence that long-term ethanol consumption is associated with angiogenesis through delicate and coordinated action of a variety of mediators.

Role of Polyphenols in Diet and Nutrition-An Updated Review

Polyphenols constitute one of the most numerous and ubiquitous groups of plant metabolites and are an integral part of both human and animal diets. The main polyphenol dietary sources are fruit and beverages (wine, tea, coffee, chocolate and beer) and to a lesser extent vegetables, dry legumes and cereals. Dietary polyphenols are mostly derivatives and/or isomers of flavones, isoflavones, flavonols, catechins and phenolic acids, and possess various biological properties. Research on the effects of dietary polyphenols on human health has developed strongly and supports a role for polyphenols in the prevention of degenerative diseases, particularly cardiovascular diseases, anti-inflammation, antiatherosclerosis, cardiovascular protection, improvement of the endothelial function, as well as inhibition of angiogenesis and cell proliferation activity. This paper covers the elaborate literature on the subject, and highlights the functions and protective effects of dietary polyphenols.