Phytochemicals: A cure for alcohol toxicity

Alcohol is a highly intoxicating substance which when consumed in large amounts produce harmful effects on the body. Blood alcohol content or blood alcohol concentration (BAC) is commonly used as a metric of alcohol intoxication for legal or medical purposes. It is usually expressed as a percentage of ethanol in the blood in units of mass of alcohol per volume of blood or mass of alcohol per mass of blood, depending on the country. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) define "binge drinking" as a pattern of drinking that brings a person’s blood alcohol concentration to 0.08 grams percent or above. This happens when men consume 5 or more drinks, and when women consume 4 or more drinks, in about 2 hours ("Quick Stats: Binge Drinking." The Centers for Disease Control and Prevention, 2008). The legal limit of blood alcohol content in India is 0.03% according to the Motor Vehicles Act, 1988. While in Kerala, a policy of zero tolerance has developed (Section 185 of Motor Vehicles Act 1988). 

According to World Health Organization, Global Status report on Alcohol and Health, 2014 38.3% of world population consume alcohol on a regular basis (World Health Organization, 2014). 30% of Indians consume alcohol frequently while 11% of Indians are moderate to heavy drinkers. The average Indian consumes 4.3 litre of alcohol per year while average rural Indian consumes 11.4 litre of alcohol per year. Organization for Economic Cooperation and Development, May 2015 reported that alcohol abuse increased by 55% between 1992 and 2012. 3.3 million deaths have been reported due to alcohol consumption. It is the major cause liver cirrhosis and failure and also poverty in India. 4

Records show that alcohol consumption per capita per week in (ml) as of 2011-12 is 120(Toddy and Country Liquor) and 27(Beer, Imported Alcohol and Wine)(World Health Organization, 2014). Chhattisgarh has set records by collecting large amount of revenue from the sale of liquor during the past 8 months. People of Chhattisgarh have consumed liquor worth Rs 24 billion and Raipur is at the top by spending Rs 3.8 billion on it. The maximum revenue came from Raipur at Rs.38,98649,791 followed by Durg at Rs 2334668184, Bilaspur (Rs 1624348236) and Rajnandgaon ( Rs 1187182340). The Chhattisgarh Cabinet has taken action against this by approving the ' Excise Policy' to exercise total control over the liquor retailing outlets (The Pioneer, 2017 ).

ABSORPTION OF ALCOHOL:

When alcohol is consumed, the alcohol is quickly absorbed in the blood by diffusion and is then transported to the tissues and throughout the water-containing portions of the body as part of the process of distribution. Some amount of alcohol is absorbed through the stomach (20 percent), while most of it is absorbed through the upper portion of the small intestine (80 percent). (Kessler et al. 1997, Lachenmeier DW et al., 2009) Empty stomach allows rapid passage of the alcohol into the small intestine while its effects are reduced due to food in the stomach especially fatty foods. Infact, a fatty meal can reduce the blood alcohol concentration upto 50%.The cells that line that small intestine and stomach are called epithelial cells. These cells have finger-like projections which project into the GI lumen and the increase the surface area for the absorption of nutrients and other molecules through the membrane. Ethanol molecules in the gut diffuse across epithelial cells, through the interstitial space, and then into nearby capillaries which are lined by endothelial cells. Ethanol moves through the water channels or pores that are created by proteins embedded in the cell membrane through a process called diffusion. This type of diffusion is called filtration because ethanol is small enough to ‘filter’ through the pores. Ethanol can also diffuse through the core of the lipid bilayer because it is slightly lipophilic and relatively small. The movement of ethanol across the cell membrane is passive transport. Once alcohol enters the capillaries, it is carried by the bloodstream into the veins where it can then be distributed throughout the entire circulation.

Figure- Ethanol diffuses passively across biological membranes.

METABOLISM OF ALCOHOL IN LIVER:

The liver is one of the largest organs in the body. It has the ability to regenerate itself. An association between alcohol consumption and liver damage is recognized. The liver is the primary site of alcohol metabolism in the body. When it is metabolized, dangerous by-products are formed which are harmful than the alcohol itself. Alcohol is highly diffusible through cell membranes and is metabolized by most tissues. Thus, its toxicity affects most organs though the primary place where alcohol is metabolized is the liver. Liver cells contain ADH (alcohol dehydrogenase), which converts alcohol to acetaldehyde through a process called oxidation. The enzyme aldehyde dehydrogenase (ALDH) rapidly oxidizes acetaldehyde to acetate. Acetate travels through the body and enters the metabolic pathways that produce energy or useful substances. Other enzymes in turn convert the acetaldehyde to carbon dioxide and water, which are excreted from the body. The usual biological role of both ADH and ALDH is to metabolize vitamin A. The microsomal enzyme oxidizing system (MEOS) is an alternate pathway for alcohol metabolism in the liver. Microsomal enzymes belong to a family of proteins called cytochromes. Some cytochromes, located in a cellular substructure called the endoplasmic reticulum detoxify harmful substances that enter the body. The MEOS oxidizes alcohol to acetaldehyde by means of a cytochrome called P450 2E1, or CYP2E1, which is found in the endoplasmic reticulum of liver cells. Normally functioning at a low level, CYP2E1 is stimulated to a higher level by the presence of alcohol. Thus, the MEOS becomes increasingly important as alcohol consumption becomes heavier and more chronic. Ethanol oxidation generates an excessive of reducing equivalents when the rate of alcohol consumption exceeds the rate at which the alcohol can be metabolized, the concentration of alcohol in the blood rises and the individual becomes intoxicated (The Alcohol Pharmacology Education Partnership, Duke University).

EFFECTS OF ALCOHOL:

Some of the harmful effects of alcohol on the body are:-

a) Infectious disease - Alcohol increases the risk of tuberculosis (JACQUELYN J. MAHER, M.D., 2002), infection with the human immunodeficiency virus (HIV) (Baliunas et al. 2010) and pneumonia (Samokhvalov et al. 2010) Alcohol affects the immune system (Rehm et al. 2009) and in case of HIV, it interferes with antiretroviral treatment (I Pandrea et al., 2010).

b) Cancer – Alcohol is carcinogenic to humans (R Baan et al., 2007). Alcohol can cause cancer of the oral cavity, pharynx, larynx, esophagus, liver, colon, rectum, and female breast. Alcohol causes cancer through variations (i.e., polymorphisms) in genes encoding enzymes responsible for ethanol metabolism (e.g., alcohol dehydrogenase, aldehyde dehydrogenase, and cytochrome P450 2E1), increased estrogen concentrations, and changes in folate metabolism and DNA repair (P Boffetta et al., 2006). The International Agency for Research on Cancer group concluded that acetaldehyde, which is a metabolized product of alcohol causes cancer of the digestive tract (Y Kawano et al., 2000).

c) Diabetes – High consumption of alcohol may cause Type II diabetes (T2DM), which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes.

d) Neuropsychiatric Disorders- The nervous system is very sensitive to alcohol. Alcohol is associated with almost all mental disorders (G Soardo et al., 2005). Conditions resulting from alcohol abuse are:-

Alcohol withdrawal syndrome- This syndrome occurs when alcohol consumption has been interrupted or suddenly diminished. It is characterized by tremulousness, hallucinations, seizures, delirium, irritation, nausea and vomiting, irregular sleep, loss of appetite, tachycardia, muscular weakness, depression, anxiousness . The causes of this syndrome are- disturbance of adaptation of alcohol, release of acetylcholine, blocking of neurotransmitters, enzyme induction, increase of slow wave sleep with the simultaneous suppression of REM sleep during increasing blood alcohol level and the predomination of REM sleep stages as rebound phenomenon during alcohol withdrawal.

Delirium tremens- It is the most common alcohol psychosis characterized by disorders of perception (visual hallucinations).Patient is sleepless and is constantly agitated.

Alcohol hallucinosis- In this case, auditory hallucinations are prevalent which the person can relate to real environment. The person is in fear, anger and depression. Suicidal attempts are common.

Wernicke-Korsakow Syndrome- Wernicke in 1881, described this disease as an illness of sudden onset characterized by paralysis of eye movements, ataxic gait and mental confusion. Korsakow’s psychosis (1887) is characterized by loss of memories, inability to form new memories or to learn, impairment of perceptual and conceptual functions and loss of spontaneity.

Seizures- Convulsive seizures are quite common in alcoholics. The occurrence of focal seizures indicate the presence of focal cerebral lesion in addition to alcoholism.

Alcoholic Cerebellar Degeneration- Problem occurs in the movement of arms and legs. Destruction of the Purkinje cells occur.

Cerebral Atrophy- Alcohol causes cortical and sub-cortical atrophy.

e) Cardiovascular Diseases- Excessive drinking of alcohol causes high blood pressure, hypertension, brain hemorrhage, heart failure and arrhythmia(LG Howes et al., 1986). Oxidative stress due to alcohol causes endothelial dysfunction (William Boggan et al., 2002). Alcohol directly inhibits the contractility of cardiac muscle in a dose-dependent manner (H Kalant et al., 1996).

f) Pancreatic Diseases- Chronic alcohol consumption increases cholesteryl esters and fatty acid ethyl esters in organelle membranes, altering the fragility of enzyme storage structures within the cell (i.e., lysosomes [L] and zymogen granules [Z]), increases digestive enzyme synthesis and blocks the release of digestive enzymes from the cell. Release of digestive enzymes from fragile L and Z granules into the cell’s interior breaks down cell components (i.e., autodigestion). In this way, alcohol consumption cause damage to the pancreas.

On seeing the present condition of alcohol abuse in India, I chose to work on the harmful effects of alcoholism on some vital organs of the body like liver and female reproductive system (ovary).

By:

Dr. Hindole Ghosh

Assistant Professor –Zoology

Kalinga University

Email Id : hindole.ghosh@kalingauniversity.ac.in

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