CLINICOEPIDEMIOLOGIC, TOXICOLOGICAL, AND SAFETY EVALUATION STUDIES ONARGEMONE OIL

Consumption of oil extracted from accidental or deliberate contaminati on of argemone seed to mustard seed is known to pose a clinical condit ion popularly referred to as Epidemic Dropsy. Several outbreaks of Epi demic Dropsy have occurred in the past in India as well as in Mauritiu s, Fiji Island, and South Africa. Clinico-epidemiological manifestatio ns of argemone oil poisoning include vomiting, diarrhea, nausea, swell ing of limbs, erythema, pitting edema, breathlessness, etc. In extreme cases, glaucoma and even death due to cardiac arrest have been encoun tered. The toxicity of argemone oil has been attributed to two of its physiologically active benzophenanthridine alkaloids, sanguinarine and dihydrosanguinarine. Histopathological studies suggest that liver, lu ngs, kidney, and heart are the target sites for argemone oil intoxicat ion. Studies have shown to elucidate the cocarcinogenic potential of a rgemone oil that can be correlated with the binding of sanguinarine wi th a DNA template. Pharmacological response in intestine revealed imme diate stimulation of tone and peristaltic movements of the gut in the sanguinarine-treated animals. Argemone oil/Sanguinarine caused a decre ase in hepatic glycogen levels which may be due to the activation of g lycogenolysis leading to an accumulation of pyruvate in the blood of E pidemic Dropsy cases. The increase in pyruvate levels causes uncouplin g of oxidative phosphorylation leading to breathlessness, as observed in patients. Sanguinarine has been shown to inhibit Na+,K+-ATPase acti vity of different organs such as brain, heart, liver, intestine, and s keletal muscle, which may be due to the interaction with the glycoside receptor site on ATPase enzyme, thereby causing a decrease in the act ive transport of glucose. Argemone oil/alkaloid showed a Type II bindi ng spectra with hepatic cytochrome P-450 (P-450) protein, thereby caus ing loss of P-450 content and an impairment of phase I and phase II en zymes. A green fluorescent metabolite of sanguinarine, benzacridine wa s detected in the milk of grazing animals. The delayed appearance of t his metabolite in urine and feces of experimental animals suggests the slow elimination of the alkaloid. Argemone oil enhances hepatic micro somal and mitochondrial lipid peroxidation, indicating that these two organelles are the sites of membrane damage. Furthermore, studies sugg est that singlet oxygen and hydroxyl radical are involved in argemone oil toxicity. Several bioantioxidants show protective effect in argemo ne oil-induced toxicity in experimental animals. The line of treatment in argemone-intoxicated epidemics has so far been only symptomatic, a nd specific therapeutic measures are still lacking, although it has be en suggested that diuretics, bioantioxidants, steroids, vitamins, calc ium- and protein-rich diet had some beneficial effects on Epidemic Dro psy cases.