Epidemic dropsy
Encyclopedia
Epidemic dropsy is a form of edema
of extremities due to intoxication
with Argemone mexicana
(Mexican prickly poppy).,..
In Northern India, epidemic dropsy occurs as a food adulterant
disease where use of mustard oil
as cooking medium is common. When mustard oil is adulterated deliberately (as in most cases) or accidental contamination with argemone oil, proteinuria
(specifically loss of albumin
) occurs, with a resultant edema as would occur in nephrotic syndrome
. Other symptoms are bilateral pitting edema of extremities headache
, nausea
, loose bowels, erythema
and breathlessness
. In severe cases fatalities are reported due to congestive heart failure
.The toxic effects of argemone oil have been attributed to the presence of benzophenanthridine alkaloids, sanguinarine
and dihydrosanguinarine
. It has been reported that the sanguinarine alkaloid content in argemone oil varies from 0.44% to 0.50%.
Besides India, widespread epidemics have been reported from Mauritius,Fiji Islands, Northwest Cape districts of South Africa, Madagascar and also from Nepal. Apart from South African study where the epidemic occurred through contamination in wheat flour, all the epidemics occurred through the consumption of mustard oil contaminated with argemone oil. In these populations mustard oil is the prime edible oil by habit and culture.
. Sanguinarine has been shown to possess pro-oxidant property in vitro towards the production of free radicals including singlet oxygen and hydrogen peroxide. Prior, in vitro studies have shown that reactive oxygen species (ROS) are involved in AO induced toxicity causing peroxidative damage of lipids in various hepatic sub-cellular fractions including microsomes and mitochondria of rats. The damage in hepatic microsomal membrane causes loss of activity of cytochrome P-450 and other membrane bound enzymes responsible for xenobiotic metabolism which leads to delayed bioelimination of sanguinarine and enhances its cumulative toxicity.Several lines of evidence have been shown to explain the mechanism of toxicity of argemone oil/alkaloid. The retention of sanguinarine in the GI tract, liver, lung, kidney, heart, and serum even after 96 hrs of exposure indicates these as the likely target sites of argemone oil toxicity.
The inhibition of Na+-K+-ATPase activity of heart by sanguinarine is due to interaction with the cardiac glycoside receptor site of the enzyme,which may be responsible for producing degenerative changes in cardiac muscle
fibers in the auricular wall of rats fed argemone oil and could be related to tachycardia and cardiac failure in Epidemic Dropsy patients.
The decrease in glycogen levels following argemone oil intoxication could be due to enhanced glycogenolysis leading to the formation of glucose-1-phosphate, which enters the glycoltic pathway resulting in accumulation of pyruvate in the blood of experimental animals and dropsy patients. The enhancement of glycogenolysis can further be supported by the interference of sanguinarine in the uptake of glucose through blocking of sodium pump via Na+-K+-ATPase and thereby inhibiting the active transport of glucose across intestinal barrier. It is well established that increased pyruvate concentration in blood uncouples oxidative phosphorylation, and this may be responsible for thickening of interalveolar septa and disorganized alveolar spaces in lungs of argemone oil-fed rats and the breathlessness as has been observed in human victims.
In vitro studies have shown that the toxicity of argemone oil is due to the production of reactive oxygen species (ROS)
and which in turn may cause enhancement in lipid peroxidation (LPO) in various hepatic subcellular fractions including microsomes and mitochondria of rats. The toxicity of sanguinarine has also been shown to be dependent on the reactivity of iminium bond with nucleophilic sites like thiol groups, present at the active sites of the enzymes and thus suggesting the electrophilic nature of the alkaloid. Recent studiese in the blood of dropsy patients has revealed that there is extensive ROS production in the argemone oil intoxication leading to depletion of total antioxidants in the body and especially lipid soluble antioxidants such as vitamin E and A (tocopherol and retinol). There is an extensive damage to the anti-oxidant defense system (anti-oxidant enzymes and anti-oxidants) of the blood.
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
of extremities due to intoxication
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
with Argemone mexicana
Argemone mexicana
Argemone mexicana is a species of poppy found in Mexico and now widely naturalized in the United States, India and Ethiopia...
(Mexican prickly poppy).,..
In Northern India, epidemic dropsy occurs as a food adulterant
Adulterant
An adulterant is a chemical substance which should not be contained within other substances for legal or other reasons. Adulterants may be intentionally added to more expensive substances to increase visible quantities and reduce manufacturing costs or for some other deceptive or malicious purpose...
disease where use of mustard oil
Mustard oil
The term mustard oil is used for three different oils that are made from mustard seeds:*A fatty vegetable oil resulting from pressing the seeds,...
as cooking medium is common. When mustard oil is adulterated deliberately (as in most cases) or accidental contamination with argemone oil, proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
(specifically loss of albumin
Human serum albumin
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein...
) occurs, with a resultant edema as would occur in nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
. Other symptoms are bilateral pitting edema of extremities headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, loose bowels, erythema
Erythema
Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
and breathlessness
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
. In severe cases fatalities are reported due to congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
.The toxic effects of argemone oil have been attributed to the presence of benzophenanthridine alkaloids, sanguinarine
Sanguinarine
Sanguinarine is a quaternary ammonium salt from the group of benzylisoquinoline alkaloids. It is extracted from some plants, including bloodroot , Mexican prickly poppy Argemone mexicana, Chelidonium majus and Macleaya cordata. It is also found in the root, stem and leaves of the opium poppy but...
and dihydrosanguinarine
Dihydrosanguinarine
Dihydrosanguinarine is an alkaloid found in the herb Corydalis adunca....
. It has been reported that the sanguinarine alkaloid content in argemone oil varies from 0.44% to 0.50%.
Besides India, widespread epidemics have been reported from Mauritius,Fiji Islands, Northwest Cape districts of South Africa, Madagascar and also from Nepal. Apart from South African study where the epidemic occurred through contamination in wheat flour, all the epidemics occurred through the consumption of mustard oil contaminated with argemone oil. In these populations mustard oil is the prime edible oil by habit and culture.
History
The earliest reference to argemone oil poisoning was made by Lyon, who reported four cases of poisoning in Calcutta in 1877 from the use of this oil in food. Since then, Epidemic Dropsy has been reported from Bengal, Bihar, Orissa, Madhya Pradesh, Haryana, Assam, J&K, Uttar Pradesh, Gujarat, Delhi and Maharashtra, mainly due to consumption of food cooked in argemone oil mixed mustard oil or occasionally by body massage with contaminated oil.The epidemic in 1998 at New Delhi, India is the largest so far, in which over 60 persons lost their lives and more than 3000 victims were hospitalized (Das and Khanna, 1998). Even after that the epidemics occurred at alarming frequency in Gwalior (2000), Kannauj (2002) and Lucknow (2005) cities of India.Argemone mexicana Linn
Argemone mexicana (family Papaveraceae), a native of West Indies and naturalized in India, is known as “Shailkanta” in Bengal and “Bharbhanda” in Uttar Pradesh. It is also popularly known as “Pivladhatura” or “Satyanashi”, meaning devastating. The plant grows wildly in mustard and other fields. Its seeds are black in colour and are similar to the dark coloured mustards seeds (Brassica nigra) in shape and size. Adulteration of argemone seeds in light yellow colored mustard seeds (Brassica compestris) can easily be detected, but these seed are rather difficult to visualize when mixed with dark coloured mustard seeds. Argemone seeds yield approximately 35% oil. Argemone seeds find use as a substitute because of the easy availability, low cost and their complete miscibility with mustard oil.Mechanism of toxicity
Sanguinarine and Dihydrosanguinarine alkaloids, present in argemone oil are the responsible etiological agents of Epidemic dropsy. Though, epidemic dropsy is known in the country for the past hundred years still there are no established effective lines of treatment.. Sanguinarine has been shown to possess pro-oxidant property in vitro towards the production of free radicals including singlet oxygen and hydrogen peroxide. Prior, in vitro studies have shown that reactive oxygen species (ROS) are involved in AO induced toxicity causing peroxidative damage of lipids in various hepatic sub-cellular fractions including microsomes and mitochondria of rats. The damage in hepatic microsomal membrane causes loss of activity of cytochrome P-450 and other membrane bound enzymes responsible for xenobiotic metabolism which leads to delayed bioelimination of sanguinarine and enhances its cumulative toxicity.Several lines of evidence have been shown to explain the mechanism of toxicity of argemone oil/alkaloid. The retention of sanguinarine in the GI tract, liver, lung, kidney, heart, and serum even after 96 hrs of exposure indicates these as the likely target sites of argemone oil toxicity.
The inhibition of Na+-K+-ATPase activity of heart by sanguinarine is due to interaction with the cardiac glycoside receptor site of the enzyme,which may be responsible for producing degenerative changes in cardiac muscle
Cardiac muscle
Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
fibers in the auricular wall of rats fed argemone oil and could be related to tachycardia and cardiac failure in Epidemic Dropsy patients.
The decrease in glycogen levels following argemone oil intoxication could be due to enhanced glycogenolysis leading to the formation of glucose-1-phosphate, which enters the glycoltic pathway resulting in accumulation of pyruvate in the blood of experimental animals and dropsy patients. The enhancement of glycogenolysis can further be supported by the interference of sanguinarine in the uptake of glucose through blocking of sodium pump via Na+-K+-ATPase and thereby inhibiting the active transport of glucose across intestinal barrier. It is well established that increased pyruvate concentration in blood uncouples oxidative phosphorylation, and this may be responsible for thickening of interalveolar septa and disorganized alveolar spaces in lungs of argemone oil-fed rats and the breathlessness as has been observed in human victims.
In vitro studies have shown that the toxicity of argemone oil is due to the production of reactive oxygen species (ROS)
and which in turn may cause enhancement in lipid peroxidation (LPO) in various hepatic subcellular fractions including microsomes and mitochondria of rats. The toxicity of sanguinarine has also been shown to be dependent on the reactivity of iminium bond with nucleophilic sites like thiol groups, present at the active sites of the enzymes and thus suggesting the electrophilic nature of the alkaloid. Recent studiese in the blood of dropsy patients has revealed that there is extensive ROS production in the argemone oil intoxication leading to depletion of total antioxidants in the body and especially lipid soluble antioxidants such as vitamin E and A (tocopherol and retinol). There is an extensive damage to the anti-oxidant defense system (anti-oxidant enzymes and anti-oxidants) of the blood.