Psychedelia.dk

Several lines of evidence have been proposed to enumerate the mechanism of toxicity of argemone oil/alkaloid. It has been suggested that the impairment of hepatic phase I and phase II enzymes by argemone oil may decrease the rate of metabolism of the alkaloid, which in turn may be responsible for the slow elimination of the compound/metabolite through urine and faeces . 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.

The other facet of argemone oil toxicity,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 damage in hepatic microsomal membrane causes loss of cytochrome P-450 and its dependent membrane bound enzymes responsible for xenobiotic metabolism thereby leading in a delay of sanguinarine excretion. 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)are highly depleted in dropsy patients. There is an extensive damage to the anti-oxidant defense system (anti-oxidant enzymes and anti-oxidants) of the blood.