Epidemic Dropsy | |
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Epidemic dropsy patients with the characteristic bilateral pitting edema of the extremities (indicated by arrows) | |
Specialty | Emergency medicine |
Epidemic dropsy is a form of edema of extremities due to poisoning by Argemone mexicana (Mexican prickly poppy). [1] [2]
Epidemic dropsy is a clinical state resulting from use of edible oils adulterated with Argemone mexicana seed oil.
Sanguinarine and dihydrosanguinarine are two major toxic alkaloids of argemone oil, which cause widespread capillary dilatation, proliferation and increased capillary permeability. When mustard oil is adulterated deliberately (as in most cases) or accidentally with argemone oil, proteinuria (specifically loss of albumin) occurs, with a resultant edema as would occur in nephrotic syndrome.
Other major symptoms are bilateral pitting edema of extremities, headache, nausea, loose bowels, erythema, glaucoma and breathlessness.
Leakage of the protein-rich plasma component into the extracellular compartment leads to the formation of edema. The haemodynamic consequences of this vascular dilatation and permeability lead to a state of relative hypovolemia with a constant stimulus for fluid and salt conservation by the kidneys. Illness begins with gastroenteric symptoms followed by cutaneous erythema and pigmentation. Respiratory symptoms such as cough, shortness of breath and orthopnoea, progressing to frank right-sided congestive cardiac failure, are seen.
Mild to moderate anaemia, hypoproteinaemia, mild to moderate renal azotemia, retinal haemorrhages, and glaucoma are common manifestations. There is no specific therapy. Removal of the adulterated oil and symptomatic treatment of congestive cardiac failure and respiratory symptoms, along with administration of antioxidants and multivitamins, remain the mainstay of treatment. [1]
Epidemic dropsy occurs as an epidemic in places where use of mustard oil from the seeds of Brassicajuncea, commonly known as Indian mustard, as a cooking medium is common. [2] This is because there is an increased chance of adulteration (with argemone oil) and consumption of such adulterated mustard oil in these areas.
Dropsy patients develop proteinuria specifically due to loss of albumin, with a resultant edema as would occur in nephrotic syndrome.
Major symptoms observed in patiesnts are bilateral pitting edema of extremities, headache, nausea, loose bowels, erythema, glaucoma and breathlessness.
Illness begins with gastroenteric symptoms followed by cutaneous erythema and pigmentation. Respiratory symptoms such as cough, shortness of breath and orthopnoea. In severe cases the before mentioned conditons will progress to frank right-sided congestive cardiac failure and death of the patient.
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 juncea ) in shape and size. Adulteration of argemone seeds in light yellow colored mustard seeds (Brassica compestris) can easily be detected, but these seeds are rather difficult to visualize when mixed with dark coloured mustard seeds.[ citation needed ]
Argemone seeds yield approximately 35% oil. Alkaloid content in argemone oil varies from 0.44% to 0.50%. Argemone seeds find use as a substitute because of the easy availability, low cost and their complete miscibility of their oil with mustard oil. [2]
Mortality is usually due to heart failure, pneumonia, respiratory distress syndrome or renal failure and is around 5%. Long-term follow-up studies are scanty so the long-term effects of argemone oil toxicity have not been documented. It has been reported that 25% of cases will have edema beyond 2 months and 10% beyond 5 months. Pigmentation of skin and excessive loss of hair, which lasted 4–5 months following the disease. The majority of patients completely recover in about 3 months. [1]
Reactive oxygen species and oxidative stress : Studies of the blood of dropsy patients has revealed that there is extensive reactive oxygen species (ROS) production (singlet oxygen and hydrogen peroxide) 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). [3] There is an extensive damage to the anti-oxidant (AO) defense system (anti-oxidant enzymes and anti-oxidants) of blood. Prior in vitro studies have shown that 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. [4] Several lines of evidence have been shown to explain the mechanism of toxicity of argemone oil/alkaloid. [5] The toxicity of sanguinarine has been shown to be dependent on the reactivity of its iminium bond with nucleophilic sites like thiol groups, present at the active sites of the enzymes and other vital proteins and thus suggesting the electrophilic nature of the alkaloid.[ citation needed ]
Pulmonary toxicity: 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 glycolytic 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 the 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. [2]
Cardiac failure: 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. [6]
Delayed clearance: Destruction of hepatic cytochrome P450 significantly affects the metabolic clearance by liver. [7] [8] The retention of sanguinarine in the gastrointestinal (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. [2]
Nitric acid test and paper chromatography test are used in the detection of argemone oil. The paper chromatography test is the most sensitive test.[ citation needed ]
Withdrawal of the contaminated cooking oil is the most important initial step. Bed rest with leg elevation and a protein-rich diet are useful. Supplements of calcium, antioxidants (vitamin C and E), and thiamine and other B vitamins are commonly used. Corticosteroids and antihistamines such as promethazine have been advocated by some investigators, but demonstrated efficacy is lacking. Diuretics are used universally but caution must be exercised not to deplete the intravascular volume unless features of frank congestive cardiac failure are present, as edema is mainly due to increased capillary permeability. Cardiac failure is managed by bed rest, salt restriction, digitalis and diuretics. Pneumonia is treated with appropriate antibiotics. Renal failure may need dialysis therapy and complete clinical recovery is seen. Glaucoma may need operative intervention, but generally responds to medical management. [1]
Besides India, widespread epidemics have been reported from Mauritius, Fiji Islands, Northwest Cape districts of South Africa, Madagascar and also from Nepal. Apart from a 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. [2]
In these cultural populations mustard oil is the prime edible oil.[ citation needed ]
The earliest reference to argemone oil poisoning was made by Lyon, [9] 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, Jammu and Kashmir, Uttar Pradesh, Gujarat, Delhi and Maharashtra, mainly due to consumption of food cooked in argemone oil mixed with mustard oil or occasionally by body massage with contaminated oil. [2]
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. [2] Few studies reported the findings in patients affected with this condition. [10]
Even after that the epidemics occurred at alarming frequency in Gwalior (2000), Kannauj (2002) and Lucknow (2005) cities of India. [3] 6 possible cases with 2 deaths were reported in Gundari village in Banaskantha district of Gujarat in India were reported in June 2021. [11]
Detoxification or detoxication is the physiological or medicinal removal of toxic substances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of drug withdrawal during which an organism returns to homeostasis after long-term use of an addictive substance. In medicine, detoxification can be achieved by decontamination of poison ingestion and the use of antidotes as well as techniques such as dialysis and chelation therapy.
Hepatotoxicity implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.
Cytochrome P450 2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals.
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds. The study of drug metabolism is the object of pharmacokinetics. Metabolism is one of the stages of the drug's transit through the body that involves the breakdown of the drug so that it can be excreted by the body.
Lamprocapnos spectabilis, bleeding heart or Asian bleeding-heart, is a species of flowering plant belonging to the fumitory subfamily (Fumarioideae) of the poppy family Papaveraceae, and is native to Siberia, northern China, Korea, and Japan. It is the sole species in the monotypic genus Lamprocapnos, but is still widely referenced under its old name Dicentra spectabilis, not to be confused with the North American native bleeding heart plants also classified under Dicentra. It is valued in gardens and in floristry for its heart-shaped pink and white flowers, borne in spring.
Argemone mexicana, also known by the common names Mexican poppy, Mexican prickly poppy, flowering thistle, cardo, and cardosanto, is a species of poppy found in Mexico and now widely naturalized in many parts of the world. An extremely hardy pioneer plant, it is tolerant of drought and poor soil, often being the only cover on new road cuttings or verges. It has bright yellow latex. It is poisonous to grazing animals, and it is rarely eaten, but it has been used medicinally by many peoples, including those in its native area, as well as the indigenous peoples of the western United States, parts of Mexico, and many parts of India. In India, during the colorful festival Holika Dahan, adults and children worship by offering flowers, and this species is in its maximum flowering phase during March when the Holi festival is celebrated. It is also referred to as "kateli ka phool" in India.
Taxus cuspidata, the Japanese yew or spreading yew, is a member of the genus Taxus, native to Japan, Korea, northeast China and the extreme southeast of Russia.
Bonny Light oil was found at Oloibiri in the Niger delta region of Nigeria in 1956 for its commercial use. Due to its features of generating high profit, it is highly demanded by refiners. Bonny light oil has an API of 32.9, classified as light oil. It is regarded as more valuable than the other oils with lower API as more high-value products are produced in the refinement. However, in Nigeria, problems due to oil spillage caused by vandalism, affects both human and the ecosystem in detrimental ways. Some experiments on animals and soil are done to figure out those impacts on organisms.
Sanguinarine is a polycyclic quaternary alkaloid. It is extracted from some plants, including the bloodroot plant, from whose scientific name, Sanguinaria canadensis, its name is derived; the Mexican prickly poppy ; Chelidonium majus; and Macleaya cordata.
Pyrrolizidine alkaloids (PAs), sometimes referred to as necine bases, are a group of naturally occurring alkaloids based on the structure of pyrrolizidine. Their use dates back centuries and is intertwined with the discovery, understanding, and eventual recognition of their toxicity on humans and animals.
Dronedarone, sold under the brand name Multaq, is a class III antiarrhythmic medication developed by Sanofi-Aventis. It was approved by the US Food and Drug Administration (FDA) in July 2009. Besides being indicated in arrhythmias, it was recommended as an alternative to amiodarone for the treatment of atrial fibrillation and atrial flutter in people whose hearts have either returned to normal rhythm or who undergo drug therapy or electric shock treatment i.e. direct current cardioversion (DCCV) to maintain normal rhythm. It is a class III antiarrhythmic drug. The FDA label includes a claim for reducing hospitalization, but not for reducing mortality, as a reduction in mortality was not demonstrated in the clinical development program. A trial of the drug in heart failure was stopped as an interim analysis showed a possible increase in heart failure deaths, in people with moderate to severe congestive heart failure.
Persin is a fungicidal toxin present in the avocado. Persin is an oil-soluble compound structurally similar to a fatty acid, a colourless oil, and it leaches into the body of the fruit from the seeds.
Dropsy, more often called edema, is the increase of interstitial fluid in any organ.
Pharmacotoxicology entails the study of the consequences of toxic exposure to pharmaceutical drugs and agents in the health care field. The field of pharmacotoxicology also involves the treatment and prevention of pharmaceutically induced side effects. Pharmacotoxicology can be separated into two different categories: pharmacodynamics, and pharmacokinetics.
Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. These symptoms include feeling tired, abdominal pain, or nausea. This is typically followed by absence of symptoms for a couple of days, after which yellowish skin, blood clotting problems, and confusion occurs as a result of liver failure. Additional complications may include kidney failure, pancreatitis, low blood sugar, and lactic acidosis. If death does not occur, people tend to recover fully over a couple of weeks. Without treatment, death from toxicity occurs 4 to 18 days later.
Pyrrolizidine alkaloidosis is a disease caused by chronic poisoning found in humans and other animals caused by ingesting poisonous plants which contain the natural chemical compounds known as pyrrolizidine alkaloids. Pyrrolizidine alkaloidosis can result in damage to the liver, kidneys, heart, brain, smooth muscles, lungs, DNA, lesions all over the body, and could be a potential cause of cancer. Pyrrolizidine alkaloidosis is known by many other names such as "Pictou Disease" in Canada and "Winton Disease" in New Zealand. Cereal crops and forage crops can sometimes become polluted with pyrrolizidine-containing seeds, resulting in the alkaloids contaminating flour and other foods, including milk from cows feeding on these plants.
Riddelliine is a chemical compound classified as a pyrrolizidine alkaloid. It was first isolated from Senecio riddellii and is also found in a variety of plants including Jacobaea vulgaris, Senecio vulgaris, and others plants in the genus Senecio.
In 1998, adulterated mustard oil poisoning in Delhi resulted in widespread dropsy and deaths of 60 people and illness of more than 3000. It was revealed that white oil, a petroleum product, was mixed with edible mustard oil. Sale of mustard in loose quantity was banned by a court order, to prevent more health hazards. In September 1998, the ban on packed mustard oil was removed after a Cabinet decision with a condition that the date of packing should be prominently displayed. Even though mustard oil is banned as an edible oil in countries like USA, Canada and EU due to its erucic acid content, the oil is widely used as an edible oil in North India, Pakistan and Nepal.
Taxine alkaloids, which are often named under the collective title of taxines, are the toxic chemicals that can be isolated from the yew tree. The amount of taxine alkaloids depends on the species of yew, with Taxus baccata and Taxus cuspidata containing the most. The major taxine alkaloids are taxine A and taxine B although there are at least 10 different alkaloids. Until 1956, it was believed that all the taxine alkaloids were one single compound named taxine.