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Epidemic DropsyArgemone mexicana L. (Papaveraceae), a native plant of the West Indies, has beennaturalized in India. It grows widely and is popularly known as satyanashi (shailkantain Bengal, bharbhanda in Uttar Pradesh). Its seeds are black in colour and similar tothe dark-coloured mustard seeds (Brassica nigra) in shape and size. While adultera-tion of argemone seeds in light yellow-co loured mustard seeds (Brassica compestris)can be easily detected, it is difficult to detect when mixed with black-coloured mus-tard seeds. Accidental admixture of argemone seeds with those of mustard, growingin the same field, does not occur as the harvesting time of mustard (February-March)and argemone (May-June) is different. Argemone seeds are rich in oil (30%-35 %)whose colour is similar to that of mustard oil.

Consumption of mustard oil contaminated with argemone seed oil is known tocause epidemic dropsy. 1,2 Argemone poisoning was first reported from Calcutta in1877. Since then, several outbreaks have occurred in different states of India as wellas in Mauritius, Fiji Islands and South Africa. Except for the South African epidemicwhich occurred because of consumption of wheat flour adulterated with argemoneseeds, all the other outbreaks were related to the intake of mustard oil contaminatedwith argemone oil. 3 Usually, epidemics in India have been reported between July andSeptember. The recent epidemic (1998) in Delhi and other states, which also startedin August, is possibly the largest in India so far.

Extensive clinico-epidemiological studies were reported from the All IndiaInstitute of Hygiene and Public Health, Calcutta and from the School of TropicalMedicine, Calcutta. The clinical manifestations of argemone oil poisoning includevomiting, diarrhoea, nausea, fever, erythema, bilateral pitting oedema of the lowerlimbs, breathlessness, tachycardia, hepatomegaly, crepitations in the lungs and galloprhythm.v' In severe cases, glaucoma" and even death due to cardiac and respiratoryfailure have been reported.P Normocytic hypochromic anaemia with increasederythrocyte sedimentation rate (ESR) is a constant feature. Pregnant women afflictedwith epidemic dropsy either abort or give birth to stillborn foetuses. Symptomssimilar to those of epidemic dropsy occur in human subjects fed argemone oil. 9Whilethis implicates the adulteration of mustard oil with argemone oil in the causation ofepidemic dropsy, little is known about the long term effects of this contamination.

S. N. Sarkar's pioneering work in 1948 attributed the toxic effects of argemone oilto two of its physiologically active benzophenanthridine alkaloids-sanguinarineand dihydrosanguinarine." Both these compounds are interconvertible by simpleoxidation and reduction processes. He reported that the alkaloid content in argemoneoil varies from 0.044 % to 0.5 %.8 While this variation may be due to the differenttechniques used for the estimation of alkaloids, further work needs to be done on therelationship between climatic and geographical factors on the toxin content of theplant.

Detection of argemone oil in mustard oil has always been a cause for concern. Anumber of tests have been developed for the detection of argemone oil. These includethe nitric acid, ferric chloride, hydrochloric acid, antimony trichloride, cupric acetateand picric acid tests. Their sensitivities range from 0.1 % to 5% of argemone oil.Methods using paper chromatography and thin layer chromatography (TLC) have asensitivity of 50 ppm of argemone oil. Researchers at the National Institute ofNutrition (NIN), Hyderabad have used TLC for quantitative estimation of sanguina-rine." The Industrial Toxicology Research Centre (ITRC), Lucknow has developeda qualitative test with a sensitivity of 100 ppm for the detection of argemone oil at thefield level. Investigators at NIN have shown the presence of sanguinarine in the serumand urine of dropsy patients. However, as sanguinarine has a strong affinity for serumproteins, its estimation in serum needs further investigation.

Experimental studies suggest that the skin, liver, lungs, kidneys and heart are thetarget sites for argemone oil intoxication.' The inhibition of pyruvate oxidation bysanguinarine has been speculated to increase the blood pyruvate concentration.However, this hypothesis is not yet established in dropsy patients. Sanguinarine

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inhibits the Na", K+-ATPase activity of the heart by interacting with the cardiacglycoside receptor site of the enzyme." In rats, the inhibition of enzyme activityprobably causes degenerative changes in the cardiac muscle fibres of the auricularwall. A similar effect could be causing tachycardia and cardiac failure in patients withdropsy. Argemone oil causes a dilatation of the smaller arterioles and capillaries.'Capillaritis' leads to the escape of serum albumin with a concomitant increase inglobulin resulting in increased capillary permeability which may be responsible foroedema and serous effusions in the pericardium, lungs and pleural cavity."

Studies from ITRC suggest that argemone oil inactivates the hepatic cytochromeP450 protein. 13This is responsible for the biotransformation ofa variety ofxenobiotics,thus impairing the clearance of argemone alkaloids from the body" resulting incumulative toxicity. A green fluorescent metabolite, benzacridine, was detected in theurine and faeces of rats and guinea pigs even 96 hours after oral intubation ofsanguinarine. 14This metabolite has also been detected in the milk of sheep grazing onargemone plants. Argemone oil has also been reported to enhance the production ofreactive oxygen species (ROS).15.16In rats, these may result in increased fibrosis,hyperplasia of bile ducts and congestion in the portal tracts along with hepatomegaly,dilated blood vessels and proliferation of endothelial cells. Several bioantioxidantshave a protective effect by scavenging the ROS in argemone oil-induced toxicity. 15.16Based on these studies, a limited trial of a combination ofbioantioxidants (riboflavinand L-tocopheroi) was conducted in dropsy patients at Barabanki.? This regimen wasadopted in several hospitals of Delhi and other states during the August 1998outbreak. Although steroid therapy has also been advocated in dropsy patients, it maybe counter-effective in the haemorrhagic state. The line of treatment in argemone-intoxicated patients has so far been symptomatic, as the mechanism of toxicity ofargemone oil is still not clear.

REFERENCESI Sarkar SL. Katakar oil poisoning. Indian Med Gar 1926;61:62-3.2 Lal RB. RoySC. Investigation into epidemiology of epidemic dropsy. I. Introductory notes and historical survey.

Indian} Med Res 1937;25:163-76.3 Manson-Bahr PEC. AptedFIC. Plant poisons. In:Manson's tropical diseases. London:Bailliere-Tindal. )982:148.4 Lal RB. Epidemic dropsy in Bihar. Indian Med Gaz 195) ;86:64-71.5 Chaudhuri RN. Clinical and experimental research. Bull Calcutta School Trop Med 1959;7: 157-65.6 Sood NN. Sachdev MS. Mohan M. Gupta SK. Sachdev HPS. Epidemic dropsy following transcutaneous absorp-

tion of Argemone mexicana oil. Trans R Soc Trop Med Hyg 1985;79:510-12.7 Kumar A. Husain F. Das M. Khanna SK. An outbreak of epidemic dropsy in the Barabanki district of Uttar

Pradesh: A limited trial for the scope of bioantioxidants in the management of symptoms. Biomed Environ Sci)992;5:251-6.

8 Das M, Khanna SK. Clinicoepidemiological, toxicological and safety evaluation studies on argemone oil. CRCCrit Rev Toxicoll997;27:273-97.

9 Lal RB, Roy SC. Investigation into epidemiology of epidemic dropsy. Further field study and controlledexperiments. Indian} Med Res 1939;27:191-203.

10 Sarkar SN. Isolation from argemone oil of dihydrosanguinarine and sanguinarine: Toxicity of sanguinarine.Nature 1948;162:265-6.

II Shenolikar IS, Babu S, Thapar GS, Ramasastri BV. Quantitative determination of argemone oil in edible oil bythin layer chromatography. Indian } Med Res 1981;75:204-7.

12 Seifen E, Adams RJ, Riemer RK. Sanguinarine: A positive inotropic alkaloid which inhibits cardiac Na+. K+ATPase. Eur} PharmacoI1979;60:373-7.

13 Upreti KK, Das M, Khanna SK. Biochemical toxicology of argemone oil. Effect on hepatic cytochrome P-450xenobiotic metabolising enzymes. J Appl Toxicol 1991;11:203-9.

14 Tandon S, Das M. Khanna SK. Biometabolic elimination of organ retention profile of argemone alkaloids,sanguinarine in rats and guinea pigs. Drug Metab Disp 1993;21:194-7.

15 Das M, Upreti KK, Khanna SK. Biochemical toxicology ofargemone oil: Role of reactive oxygen species in ironcatalysed lipid peroxidation. Bull Environ Contam Toxicoll991 ;46:422-30.

16 Upreti KK, Das M, Khanna SK. Role of antioxidants and scavengers on argemone oil-induced toxicity in rats.Arch Environ Contam Toxicoll99I;20:531-7.

MUKUL DAS

SUBHASH K. KHANNA

Food Toxicology DivisionIndustrial Toxicology Research Centre

LucknowUttar Pradesh